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The literature presents insufficient data evaluating the displacement and micromotion effects resulting from the combined use of tooth-implant connections in fixed partial dentures. Analyzing the biomechanical behavior of tooth-implant fixed partial denture (FPD) prothesis is vital for achieving an optimum design and successful clinical implementation. The objective of this study was to determine the relative significance of connector design on the displacement and micromotion of tooth-implant-supported fixed dental prostheses under occlusal vertical loading. A unilateral Kennedy class I mandibular model was created using a 3D reconstruction from CT scan data. Eight simulated designs of tooth-implant fixed partial dentures (FPDs) were split into two groups: Group A with rigid connectors and Group B with non-rigid connectors. The models were subjected to a uniform vertical load of 100 N. Displacement, strain, and stress were computed using finite element analysis. The materials were defined as isotropic, homogeneous, and exhibiting linear elastic properties. This study focused on assessing the maximum displacement in various components, including the bridge, mandible, dentin, cementum, periodontal ligament (PDL), and implant. Displacement values were predominantly higher in Group B (non-rigid) compared to Group A (rigid) in all measured components of the tooth-implant FPDs. Accordingly, a statistically significant difference was observed between the two groups at the FPD bridge (p value = 0.021 *), mandible (p value = 0.021 *), dentin (p value = 0.043 *), cementum (p value = 0.043 *), and PDL (p value = 0.043 *). Meanwhile, there was an insignificant increase in displacement values recorded in the distal implant (p value = 0.083). This study highlighted the importance of connector design in the overall stability and performance of the prosthesis. Notably, the 4.7 mm × 10 mm implant in Group B showed a displacement nearly 92 times higher than its rigid counterpart in Group A. Overall, the 5.7 mm × 10 mm combination of implant length and diameter showcased the best performance in both groups. The findings demonstrate that wider implants with a proportional length offer greater resistance to displacement forces. In addition, the use of rigid connection design provides superior biomechanical performance in tooth-implant fixed partial dentures and reduces the risk of micromotion with its associated complications such as ligament overstretching and implant overload, achieving predictable prognosis and enhancing the stability of the protheses.

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BACKGROUND Classical hemophilia A, an X-linked recessive disorder, is characterized by an inability to produce factor VIII in normal quantities. This condition, also leading to factor IX deficiency, underpins the bleeding disorder known as hemophilia A. Among the complications of this illness, spontaneous retroperitoneal hematoma is rare but can be associated with congenital coagulopathies such as von Willebrand disease or hemophilia A. This type of spontaneous internal bleeding has been the subject of a limited number of studies. CASE REPORT A 38-year-old man with a known diagnosis of hemophilia A presented to the Emergency Department exhibiting acute pain in the right lower abdomen. A computed tomography scan of the abdomen identified a right-sided retroperitoneal mass, suspected to be a hematoma. Within 7 h after admission, the patient experienced significant drops in the hemoglobin level and platelet count. He was administered packed red blood cells, fresh frozen plasma, and platelet transfusions prior to transfer to the Intensive Care Unit. There, he was treated with factor VIII and recombinant factor VIIa, coupled with stringent monitoring. Following clinical and laboratory findings and stabilization, he was discharged with specific medications, and a follow-up appointment was scheduled. CONCLUSIONS Spontaneous retroperitoneal hematoma in patients with hemophilia A is a rare and grave emergency. This case underscores the need for precise diagnostic approaches, tailored management strategies, and vigilant surveillance to prevent and mitigate the potentially life-threatening complications associated with spontaneous hemorrhage in this population.

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PMMA/PEG and PMMA/PEG doped with SiO2, TiO2, and Al2O3 were fabricated using the solution-casting technique. The composites were characterized by X-ray diffraction and scanning electron microscopy (FE-SEM), which revealed that the amorphous nature of PMMA/PEG blend doped with Al2O3 was hindered by the crystalline nature of those doped with SiO2 and TiO2. The absorption of PMMA/PEG blend doped with Al2O3 is higher, band gap energies were decreased from 4.90 eV for PMMA/PEG blend to 4.03 eV, 3.09 eV, and 2.09 eV for SiO2, TiO2, and Al2O3 doped PMMA/PEG blend, respectively. The dielectric constant, ε' has a high value (2 × 104) for samples PMMA/PEG and SiO2/PMMA/PEG. While dielectric loss ε ″ -values decreased to < 100 for TiO2/PMMA/PEG and Al2O3/PMMA/PEG. Further, the fabricated composite SiO2/PMMA/PEG led to improvement the optical and dielectric properties compared with PMMA/PEG for optoelectronic such as manufacturing of optical fiber cables application. The results show TiO2/PMMA/PEG and Al2O3/PMMA/PEG are multifunctional can be used as low-permittivity nanodielectric and substrates to design the next generation of flexible electronic devices.

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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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OBJECTIVE: The objective of this study was to compare the effectiveness and safety of anti-Xa-guided management versus aPTT-guided management of intravenous (IV) unfractionated heparin (UFH) in patients with a durable ventricular assist device (VAD). MATERIALS AND METHODS: This was a retrospective study conducted at a single academic medical center. Patients were included if they had a durable VAD and were managed using aPTT-guided UFH management from May 2019 to May 2020 or were managed using anti-Xa-guided UFH management from May 2021 to December 2021. The primary outcome of the study was the median time to goal anticoagulation post-initiation of UFH. Secondary outcomes included the percentage of time within the therapeutic range and the incidence of thromboembolic and bleeding complications. RESULTS: The study included 23 patients, 12 of whom were managed using anti-Xa-guided UFH, and 11 were managed using aPTT-guided UFH. The treatment arm using anti-Xa-guided UFH demonstrated a faster time to therapeutic anticoagulation goal range with a median time of 21.3 h [IQR = 12.2-34.8] compared to 37.3 h [IQR = 41-74] in the aPTT-guided UFH treatment arm (P = 0.03). In addition, the anti-Xa-guided UFH arm had a higher percentage of time within the therapeutic range, 76 % [IQR = 64.25-96.25] compared to 53 % [IQR = 41-74] in the aPTT-guided UFH arm (P = 0.04). Both arms had no significant differences in major bleeding events (P = 0.59) or clinically relevant minor bleeding events (P = 0.60) among patients. There was no incidence of thromboembolic events in either treatment arm. CONCLUSION: Based on this single-center experience, anti-Xa-guided UFH management resulted in a faster time to therapeutic anticoagulation and a longer time within the desired therapeutic range. The results suggest that anti-Xa-guided monitoring may be superior to UFH-guided monitoring in patients with a durable VAD.

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AIM: The neutrophil-to-lymphocyte ratio (NLR) is commonly used as a prognostic indicator for microbiological and inflammatory conditions in clinical settings. However, the quotient to albumin levels, which is another nutritional and clinical predictor, may also have an interesting diagnostic and prognostic value. This study aimed to primarily investigate the predictive performances of the neutrophils to albumin and lymphocytes ratio (NALR) compared to the NLR in predicting poor outcomes during hospital admission, particularly the decomposition of respiratory, renal, liver, and circulatory systems, resulting in longer hospital stays or mortality. METHODS: An observational study was performed on a cohort of 270 hospitalised patients admitted to Rashid bin Al-Hussein Military Hospital during the period from October 2023 to early November 2023. The study specifically targeted adult patients (age >17 years) who had a minimum of 80% availability of their initial and follow-up data during admission. We dichotomised all eligible test patients into two groups: Group I, which represented better outcomes of interest, and Group II, which represented poorer outcomes of interest. Statistically, we conducted binary logistic, receiver operating, and sensitivity analyses to explore the predictive performances and indices for NALR and NLR. We also conducted chi-square and independent T analyses to uncover the distribution rates of the independent variables across Groups I and II. We considered a p-value of less than 0.05 as the level of significance. RESULTS: Out of a total sample size of 270, 82 patients (30.37%) were allocated to Group I, and 188 patients (69.63%) were allocated to Group II. Males outnumbered females in this study by 184 (68.1%) to 86 (31.9%). Patients in the study had an average age of 58.08±10.02 years. The average hospitalisation took 13.71±6.38 days, significantly longer in Group II compared to Group I (15.43±6.76 days vs. 9.77±2.69 days, p-value<0.05). We found that the area under the receiver operating characteristic (ROC) curves was estimated at [0.808±0.031 (0.748-0.868), p-value=0.000] and [0.667±0.034 (0.601-0.733), p-value=0.000] for NALR and NLR, respectively. The optimal operating thresholds for NALR and NLR were 1.5 and 5.37, with sensitivities and specificities of 86.7% versus 73.4% and 70.73% versus 70.73%, respectively. CONCLUSION: The proposed NALR showed superior predictive performance, sensitivity, and correlation compared to the parent NLR. Both tools can be used in clinical practice to prioritise clinical and pharmacotherapeutics for hospitalised patients based on unfavourable outcomes.

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This study examined the influence of nanomaterials (NMs) on the organization of membrane lipids and the resulting morphological changes. The cell plasma membrane is heterogeneous, featuring specialized lipid domains in the liquid-ordered (Lo) phase surrounded by regions in the liquid-disordered (Ld) phase. We utilized model membranes composed of various lipids and lipid mixtures in different phase states to investigate the interactions between the NMs and membrane lipids. Specifically, we explored the interactions of pure chitosan (CS) and CS-modified nanocomposites (NCs) with ZnO, CuO, and SiO2 with four lipid mixtures: egg-phosphatidylcholine (EggPC), egg-sphingomyelin/cholesterol (EggSM/Chol), EggPC/Chol, and EggPC/EggSM/Chol, which represent the coexistence of Ld, Lo, and Ld/Lo, respectively. The data show that CS NMs increase the membrane lipid order at glycerol level probed by Laurdan spectroscopy. Additionally, the interaction of CS-based NMs with membranes leads to an increase in bending elasticity modulus, zeta potential, and vesicle size. The lipid order changes are most significant in the highly fluid Ld phase, followed by the Lo/Ld coexistence phase, and are less pronounced in the tightly packed Lo phase. CS NMs induced egg PC vesicle adhesion, fusion, and shrinking. In heterogeneous Lo/Ld membranes, inward invaginations and vesicle shrinking via the Ld phase were observed. These findings highlight mechanisms involved in CS NM-lipid interactions in membranes that mimic plasma membrane heterogeneity.

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OBJECTIVES: The study aimed to assess the effect of these biomarkers on a sample of children with autism spectrum disorder (ASD) to help in early diagnosis and intervention. METHODS: A total of 71 autistic patients and 65 normal controls were enrolled in this study. Their ages ranged from 5 to 11 years (mean ± SD 7.47 ± 3.81). Childhood Autism Rating Scale (CARS) was assessed for all patients and controls. Assessment of oxidative stress, monocyte chemoattractant protein-1, B-cell lymphoma 2, S-adenosylhomocysteine (SAH), and apelin was performed. RESULTS: Oxidative stress (oxidized low-density lipoprotein and malonaldehyde) increased while antioxidant paraoxonase (PON) decreased. Monocyte chemoattractant protein-1, B-cell lymphoma 2, and S-adenosylhomocysteine (SAH) were all elevated whereas, apelin was downregulated. CONCLUSIONS: It is important to note that many factors that may contribute to ASD including genetic factors. To open the door for novel treatment strategies, it is still necessary to precisely understand how oxidative stress, chemokines, apoptosis, and methylation capability affect the metabolism of people with ASD.

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Parkinsonism is an age-related neurodegenerative illness that affects motor coordination leading to loss of dopaminergic neurons. Many medications are used for the treatment of Parkinson's disease but are only symptomatic and have a limited effect on the progression of this ailment. Therefore, bioactive compounds which derived from plants have been examined for their ability to improve the neuronal damage and cell death happened in parkinsonian patients. In this study the iridoids-rich fraction isolated from Pentas lanceolata (PIRF) leaves was investigated for its phytoconstituents. Seven iridoids (1-7) and one flavonol diglycoside (8) were isolated, and their chemical structures were achieved by 1H and 13C nuclear magnetic resonance and ESI-MS spectral data. Compound 1 (6ß,7ß-epoxy-8-epi-splendoside) and 5 (gaertneroside) were isolated for the first time from Pentas genus as well as compound 8 (kaempferol-3-O-robinobioside). The current study aims to investigate the possible anti-parkinsonian effect of PIRF using a rotenone model of Parkinsonism in mice. Behavioural tests (wirehanging, stair and wooden-walking tests) were done to examine the motor coordination in mice after treatment. Biochemical and histopathological examinations for brain striatum in different groups were also evaluated. Results revealed that rotenone-treated mice had poor motor functions described by depletion of dopamine and Ach levels, a significant increase in proinflammatory cytokines, IL-1B, TNF-α and Mcp-1 and oxidative biomarkers with subsequent reduction in antioxidant mediators. Disorganization of striatum, degenerated neurocytes, slight vacuolation, shrunken neurons with pyknotic nuclei and apoptotic cells are displayed by histopathological examinations. Treatment with PIRF ameliorates the neurodegeneration-induced by rotenone in the brain of mice. The anti-parkinsonian effect of PIRF could be attributed to their bioactive constituents of iridoids.

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Infectious coryza (IC) is an acute upper respiratory disease of chicken caused by Avibacterium (A.) paragallinarum. This disease results in an increased culling rate in meat chicken and a marked decrease in egg production (10% to more than 40%) in laying and breeding hens. Vaccines were first used against IC and effectively controlled the disease. Nanotechnology provides an excellent way to develop a new generation of vaccines. NPs have been widely used in vaccine design as adjuvants and antigen delivery vehicles and as antibacterial agents; thus, they can be used as inactivators for bacterial culture. In this research, the antibacterial effects of several nanoparticles (NPs), such as silicon dioxide with chitosan (SiO2-CS), oleoyl-chitosan (O.CS), silicon dioxide (SiO2), and iron oxide (Fe3O4), on A. paragallinarum were studied. Additionally, different A. paragallinarum vaccines were made using the same nanomaterials at a concentration of 400 µg/ml to help control infectious coryza disease in chicken. A concentration of 400 µg/ml of all the NPs tested was the best concentration for the inactivation of A. paragallinarum. Additionally, this study showed that the infectious coryza vaccine adjuvanted with SiO2 NPs had the highest immune response, followed by the infectious coryza vaccine adjuvanted with Fe3O4 NPs, the infectious coryza vaccine adjuvanted with SiO2-CS NPs, and the infectious coryza vaccine adjuvanted with O.CS NPs in comparison with the infectious coryza vaccine adjuvanted with liquid paraffin (a commercial vaccine).

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The present work was designed to synthesize Ag2O-supported MgO/rGO nanocomposites (NCs) via green method using Phoenix leaf extract for improved photocatalytic and anticancer activity. Green synthesized Ag2O-supported MgO/rGO NCs were characterized through X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), Raman, ultraviolet-visible (UV-vis) spectroscopy, and photoluminescence (PL) spectroscopy, and gas chromatography-mass spectroscopy (GC-MS) was applied to examine the chemical components of the Phoenix leaf extract. Characterization data confirmed the preparation of MgO NPs, Ag2O-MgO NCs, and Ag2O-MgO/rGO NC with particle size of 26-28 nm. UV-vis study exhibited that the band gap energy of MgO NPs, Ag2O-MgO NCs, and Ag2O-MgO/rGO NC were in the range of 3.53-3.43 eV. The photocatalytic results showed that the photodegradation of Rh B dye of Ag2O-supported MgO/rGO NCs (82.81%) was significantly higher than pure MgO NPs. Additionally, the biological response demonstrates that the Ag2O-supported MgO/rGO NCs induced high cytotoxicity against MCF-7 cancer cells for 24 h and 48 h compared with both pure MgO NPs and Ag2O-MgO NCs. This study suggests that the adding of Ag2O and rGO sheets played significant role in the enhanced photocatalytic and anticancer performance of MgO NPs.

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OBJECTIVE: To study the safety and efficacy of intravitreal infliximab administered at the conclusion of pars plana vitrectomy (PPV) in the treatment of proliferative vitreoretinopathy (PVR) associated with rhegmatogenous retinal detachment (RRD). DESIGN: Randomized controlled phase II clinical trial. SUBJECTS: Patients with primary RRD and grade C PVR, according to the updated Retina Society Classification. METHODS: Sixty-six patients were randomized in a 1:1 ratio to undergo PPV and silicone oil (SO) injection with or without intravitreal injection of 1 mg/0.05 mL of infliximab in the air-filled globe before SO injection at PPV conclusion. Surgeons were masked to treatment allocation until PPV conclusion. MAIN OUTCOME MEASURES: The primary outcome measure was anatomic success (defined as complete retinal reattachment without a tamponade at 6 months post SO removal). Secondary outcome measures were final best-corrected visual acuity (BCVA), single-operation success rate (SOSR), rate of recurrent detachment, central macular thickness (CMT) by macular OCT, macular function by multifocal electroretinogram, and macular vascular density (VD) by OCT angiography. RESULTS: Sixty eyes of 60 patients, 30 eyes in each group, completed the study. At baseline, there were no differences regarding age, gender, history of trauma, lens status, duration of RRD, BCVA, intraocular pressure (IOP), intraocular inflammation (IOI), detachment extent in clock hours, number/size of breaks, presence of vitreous hemorrhage, axial length, or grade/extent of PVR between both groups. For the outcome measures, 30 eyes in the infliximab group achieved anatomic success vs. 29 eyes in the control group. The SOSR was higher in the infliximab group (26) vs. the control (23), but this was not statistically significant (P = 0.317). Final logarithm of the minimum angle of resolution BCVA was better in the infliximab group (mean, 0.96; standard deviation [SD], 0.4; Snellen equivalent ≈ 20/180) vs. the control (mean, 1.14; SD, 0.4); Snellen equivalent ≈ 20/280; P = 0.044). There were no differences regarding IOP, IOI, time of SO removal, macular function, CMT, or VD. CONCLUSIONS: Pars plana vitrectomy with SO tamponade with or without intravitreal infliximab is effective in treating PVR-associated RRD. Infliximab may be associated with modest improvement in final visual outcomes but not anatomic outcomes. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

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The unfolded protein response pathways (UPR), autophagy, and compartmentalization of misfolded proteins into inclusion bodies are critical components of the protein quality control network. Among inclusion bodies, aggresomes are particularly intriguing due to their association with cellular survival, drug resistance, and aggresive cancer behavior. Aggresomes are molecular condensates formed when collapsed vimentin cages encircle misfolded proteins before final removal by autophagy. Yet significant gaps persist in the mechanisms governing aggresome formation and elimination in cancer cells. Understanding these mechanisms is crucial, especially considering the involvement of LC3A, a member of the MAP1LC3 family, which plays a unique role in autophagy regulation and has been reported to be epigenetically silenced in many cancers. Herein, we utilized the tetracycline-inducible expression of LC3A to investigate its role in choroid plexus carcinoma cells, which inherently exhibit the presence of aggresomes. Live cell imaging was employed to demonstrate the effect of LC3A expression on aggresome-positive cells, while SILAC-based proteomics identified LC3A-induced protein and pathway alterations. Our findings demonstrated that extended expression of LC3A is associated with cellular senescence. However, the obstruction of lysosomal degradation in this context has a deleterious effect on cellular viability. In response to LC3A-induced autophagy, we observed significant alterations in mitochondrial morphology, reflected by mitochondrial dysfunction and increased ROS production. Furthermore, LC3A expression elicited the activation of the PERK-eIF2α-ATF4 axis of the UPR, underscoring a significant change in the protein quality control network. In conclusion, our results elucidate that LC3A-mediated autophagy alters the protein quality control network, exposing a vulnerability in aggresome-positive cancer cells.

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BACKGROUND: Recent guidelines recommend using direct oral anticoagulants (DOACs) as first-line agents in patients with non-valvular atrial fibrillation (NVAF). Research is currently investigating the use of Apixaban in underweight patients, with some results suggesting altered pharmacokinetics, decreased drug absorption, and potential overdosing in this population. This study examined the effectiveness and safety of standard Apixaban dosing in adult patients with atrial NVAF weighing less than 50 kg. METHODS: This is a retrospective cohort study conducted at King Abdulaziz Medical City (KAMC); adult patients with a body mass index (BMI) below 25 who received a standard dose of Apixaban (5 mg twice daily) were categorized into two sub-cohorts based on their weight at the time of Apixaban initiation. Underweight was defined as patients weighing ≤ 50 kg, while the control group (Normal weight) comprised patients weighing > 50 kg. We followed the patients for at least one year after Apixaban initiation. The study's primary outcome was the incidence of stroke events, while secondary outcomes included bleeding (major or minor), thrombosis, and venous thromboembolism (VTE). Propensity score (PS) matching with a 1:1 ratio was used based on predefined criteria and regression model was utilized as appropriate. RESULTS: A total of 1,433 patients were screened; of those, 277 were included according to the eligibility criteria. The incidence of stroke events was lower in the underweight than in the normal weight group at crude analysis (0% vs. 9.1%) p-value = 0.06), as well in regression analysis (OR (95%CI): 0.08 (0.001, 0.76), p-value = 0.002). On the other hand, there were no statistically significant differences between the two groups in the odds of major and minor bleeding (OR (95%CI): 0.39 (0.07, 2.03), p-value = 0.26 and OR (95%CI): 1.27 (0.56, 2.84), p-value = 0.40, respectively). CONCLUSION: This exploratory study revealed that underweight patients with NVAF who received standard doses of Apixaban had fewer stroke events compared to normal-weight patients, without statistically significant differences in bleeding events. To confirm these findings, further randomized controlled trials with larger sample sizes and longer observation durations are required.

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When populations colonise new environments, they may be exposed to novel selection pressures but also suffer from extensive genetic drift due to founder effects, small population sizes and limited interpopulation gene flow. Genomic approaches enable us to study how these factors drive divergence, and disentangle neutral effects from differentiation at specific loci due to selection. Here, we investigate patterns of genetic diversity and divergence using whole-genome resequencing (>22× coverage) in Berthelot's pipit (Anthus berthelotii), a passerine endemic to the islands of three north Atlantic archipelagos. Strong environmental gradients, including in pathogen pressure, across populations in the species range, make it an excellent system in which to explore traits important in adaptation and/or incipient speciation. First, we quantify how genomic divergence accumulates across the speciation continuum, that is, among Berthelot's pipit populations, between sub species across archipelagos, and between Berthelot's pipit and its mainland ancestor, the tawny pipit (Anthus campestris). Across these colonisation timeframes (2.1 million-ca. 8000 years ago), we identify highly differentiated loci within genomic islands of divergence and conclude that the observed distributions align with expectations for non-neutral divergence. Characteristic signatures of selection are identified in loci associated with craniofacial/bone and eye development, metabolism and immune response between population comparisons. Interestingly, we find limited evidence for repeated divergence of the same loci across the colonisation range but do identify different loci putatively associated with the same biological traits in different populations, likely due to parallel adaptation. Incipient speciation across these island populations, in which founder effects and selective pressures are strong, may therefore be repeatedly associated with morphology, metabolism and immune defence.

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Introduction Delirium is a common and serious neuropsychiatric disorder, of acute onset, present at any age, but more common in older adults, and very common in clinical practice. It combines mental and behavioral symptoms with a fluctuating course, with worsening of the condition in the afternoon and at night, with important repercussions on increased mortality, greater risk of cognitive impairment, and hospitalization costs. Delirium's impact extends to patients, families, and healthcare systems, emphasizing the need for public awareness and education in Saudi Arabia. Methodology It is a cross-sectional conducted in Saudi Arabia that aims to assess knowledge, risk factors, and attitudes regarding delirium among all Saudi and non-Saudi residents aged 18 and older. A 36 self-administered questionnaire, standardized Nordic, was used. Data were cleaned in Microsft Excel (Microsoft Corporation, USA) and analyzed using IBM SPSS Statistics (IBM Corp., Armonk, NY). This study was conducted in Saudi Arabia from May 2023 till March 2024. Results Our study involved 1,470 participants from Saudi Arabia, primarily females (79.1%), Saudi nationals (89.9%), and unmarried individuals (65.4%). Most participants were aged 18-24 (59.5%) and held bachelor's degrees (57.3%). Commonly recognized delirium risk factors included increasing age (63.3%), dementia (58.2%), and longer ICU stays (48.7%). The participants showed moderate knowledge of delirium symptoms and consequences. Attitudes varied, with many agreeing that delirium requires intervention (30.7%) but fewer considering it preventable (17.1%). Sociodemographic factors, including gender and age, significantly influenced knowledge and attitudes, while education levels did not. Conclusion Our study found that gender and age influenced knowledge and attitudes, highlighting the importance of targeted education. Future research should further investigate the effectiveness of such interventions in enhancing knowledge and awareness and promoting preventive actions.

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The purpose of the present study is to enhance the anticancer and biocompatibility performance of TiO2 NPs, ZnO NPs, ZnO-TiO2 (NCs), and ZnO-TiO2/reduced graphene oxide (RGO) NCs against two types of human cancer (HCT116) and normal (HUVCE) cells. A novel procedure for synthesizing ZnO-TiO2/RGO NCs has been developed using Senna surattensis extract. The improved physicochemical properties of the obtained samples were investigated using different techniques such as XRD, TEM, SEM, XPS, FTIR, DLS and UV-visible spectroscopy. XRD results showed that the addition of ZnO and RGO sheets affects the crystal structure and phase of TiO2 NPs. SEM and TEM images displayed that the TiO2 NPs and ZnO NPs were small with uniform spherical morphology in the prepared ZnO-TiO2/RGO NCs. Besides, it is shown that ZnO-TiO2 NCs anchored onto the surface of RGO sheets with a particle size of 14.80 ± 0.5 nm. XPS data confirmed the surface chemical composition and oxidation states of ZnO-TiO2/RGO NCs. Functional groups of prepared NPs and NCs were determined using FTIR spectroscopy. DLS data confirmed that the addition of ZnO and RGO sheets improves the negative surface charge of the prepared pure TiO2 NPs (-22.51 mV), ZnO NPs (-18.27 mV), ZnO-TiO2 NCs (-30.20 mV), and ZnO-TiO2/RGO NCs (-33.77 mV). Optical analysis exhibited that the bandgap energies of TiO2 NPs (3.30 eV), ZnO NPs (3.33 eV), ZnO-TiO2 NCs (3.03 eV), and ZnO-TiO2/RGO NCs (2.78 eV) were further enhanced by adding ZnO NPs and RGO sheets. This indicates that the synthesized samples can be applied to cancer therapy and environmental remediation. The biological data demonstrated that the produced ZnO-TiO2/RGO NCs show a more cytotoxic effect on HCT116 cells compared to pure TiO2 NPs and ZnO-TiO2 NCs. On the other hand, these NCs displayed the lowest level of toxicity towards normal HUVCE cells. These results indicate that the ZnO-TiO2/RGO NCs have strong toxicity against HCT116 cells and are compatible with normal cells. Our results show that the plant extract enhanced the physicochemical properties of NPs and NCs compared with the traditional chemical methods for synthesis. This study could open new avenues for developing more effective and targeted cancer treatments.

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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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Depression is a debilitating mental disease that negatively impacts individuals' lives and society. Novel hypotheses have been recently proposed to improve our understanding of depression pathogenesis. Impaired neuroplasticity and upregulated neuro-inflammation add-on to the disturbance in monoamine neurotransmitters and therefore require novel anti-depressants to target them simultaneously. Recent reports demonstrate the antidepressant effect of the anti-diabetic drug liraglutide. Similarly, the natural flavonoid naringenin has shown both anti-diabetic and anti-depressant effects. However, the neuro-pharmacological mechanisms underlying their actions remain understudied. The study aims to evaluate the antidepressant effects and neuroprotective mechanisms of liraglutide, naringenin or a combination of both. Depression was induced in mice by administering dexamethasone (32 mcg/kg) for seven consecutive days. Liraglutide (200 mcg/kg), naringenin (50 mg/kg) and a combination of both were administered either simultaneously or after induction of depression for twenty-eight days. Behavioral and molecular assays were used to assess the progression of depressive symptoms and biomarkers. Liraglutide and naringenin alone or in combination alleviated the depressive behavior in mice, manifested by decrease in anxiety, anhedonia, and despair. Mechanistically, liraglutide and naringenin improved neurogenesis, decreased neuroinflammation and comparably restored the monoamines levels to that of the reference drug escitalopram. The drugs protected mice from developing depression when given simultaneously with dexamethasone. Collectively, the results highlight the usability of liraglutide and naringenin in the treatment of depression in mice and emphasize the different pathways that contribute to the pathogenesis of depression.

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Chitosan-based nanocomposites (CS NCs) are gaining considerable attention as multifaceted antifungal agents. This study investigated the antifungal activity of NCs against two phytopathogenic strains: Fusarium solani (F. solani) and Alternaria solani (A. solani). Moreover, it sheds light on their underlying mechanisms of action. The NCs, CS-ZnO, CS-CuO, and CS-SiO2, were characterized using advanced methods. Dynamic and electrophoretic light scattering techniques revealed their size range (60-170 nm) and cationic nature, as indicated by the positive zeta potential values (from +16 to +22 mV). Transmission electron microscopy revealed the morphology of the NCs as agglomerates formed between the chitosan and oxide components. X-ray diffraction patterns confirmed crystalline structures with specific peaks indicating their constituents. Antifungal assessments using the agar diffusion technique demonstrated significant inhibitory effects of the NCs on both fungal strains (1.5 to 4-fold), surpassing the performance of the positive control, nystatin. Notably, the NCs exhibited superior antifungal potency, with CS-ZnO NCs being the most effective. A. solani was the most sensitive strain to the studied agents. Furthermore, the tested NCs induced oxidative stress in fungal cells, which elevated stress biomarker levels, such as superoxide dismutase (SOD) activity and protein carbonyl content (PCC), 2.5 and 6-fold for the most active CS-CuO in F. solani respectively. Additionally, they triggered membrane lipid peroxidation up to 3-fold higher compared to control, a process that potentially compromises membrane integrity. Laurdan fluorescence spectroscopy highlighted alterations in the molecular organization of fungal cell membranes induced by the NCs. CS-CuO NCs induced a membrane rigidifying effect, while CS-SiO2 and CS-ZnO could rigidify membranes in A. solani and fluidize them in F. solani. In summary, this study provides an in-depth understanding of the interactions of CS-based NCs with two fungal strains, showing their antifungal activity and offering insights into their mechanisms of action. These findings emphasize the potential of these NCs as effective and versatile antifungal agents.

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