Creating a master training rotation schedule for emergency medicine residents and challenges in using artificial intelligence.

BACKGROUND: The allocation of resident physicians to clinical rotations presents a complex challenge that requires balancing multiple objectives with the goals of providing optimal patient care, maintaining adequate departmental staffing, and maximizing residents' training experience. While adhering to governing guidelines and training regulations, these physicians must comply with curricular milestones and educational goals for progression that must be achieved within specific time constraints. This manuscript reports on how to create annual master rotation schedules to meet the training requirements for 60 residents, while addressing the requirements detailed above. METHODS: Trainees in the field of Emergency Medicine have to meet variable essential annual curricula requirements. Methods of preparing rotations in different Emergency Departments are presented which usually need early planning to ensure the best coordination and number allocation among the different internal and external collaborative departments. This off-institution and off-service external rotation is an educational necessity regulated by the Saudi Commission of Health Sciences to maximize residents' exposure and meet the expected educational milestones unique to Emergency Medicine training. RESULTS: We report how to create annual master rotation schedules to meet the training requirements for 60 Emergency Medicine residents, while maintaining steady adequate departmental staffing and accommodating the different external rotation capacities, a task that is usually handled by the chief residents and program director. Although some parts of this process can be performed by using scheduling software or with particular decision support management systems, many steps are still filtered and checked manually. External circumstances mandate changes in schedules that require last-minute changes which may overrule training restrictions and make them unfeasible. CONCLUSION: To create such an agile schedule, we maintain a standardized template with preset blocks and rotations. Residents can choose the most suitable track that meets their preference for year-long rotation blocks. Thus, we minimize the individual variability in the preset allocations, guarantee an even distribution, give equal chances to each resident to accommodate and approximate their individual preferences, and decrease the overall workload and time consumed annually.

Rare Case of Adrenal Hemangioma Discovered Incidentally during Renal Colic Investigation.

BACKGROUND Hemangiomas of the adrenal gland are rare benign non-functional tumors arising from the gland's vascular endothelium. Adrenal hemangiomas are rare in clinical settings, often discovered incidentally during an unrelated diagnostic investigation. CASE REPORT A 39-year-old man presented with a heterogeneous, enhancing 4.56×4.24×3.9-cm mass originating from the right adrenal gland's lateral limb, discovered incidentally on computed tomography (CT) to investigate renal colic. He was routinely followed up for 2 years with serial CT scans; the mass exhibited considerable growth compared with baseline, with a relatively stable appearance with hyperdense soft tissue component, fat, and foci of calcification. Dexamethasone suppression test demonstrated suppressed cortisol response, indicating a non-functional mass. Therefore, laparoscopic right adrenalectomy was performed, owing to the benign nature of the preoperative diagnosis of myelolipoma and mass size. The patient experienced an uneventful recovery, with no perioperative complications. The resected mass was 5×4×4 cm in size and weighed 30 g. Histopathology confirmed adrenal hemangioma. Serial sectioning revealed an encapsulated lesion with heterogeneous solid and cystic surfaces. Light microscopy examination showed dilated and congested vascular channels lined by flattened endothelium. Focal mature adipose tissue was seen. CONCLUSIONS The infrequent occurrence of adrenal hemangiomas and their nonspecific clinical and radiological presentation results in a considerable diagnostic challenge and, often, misdiagnosis. Surgical resection is usually necessary to exclude malignant disease, alleviate pressure-related symptoms, and decrease risk of retroperitoneum hemorrhage. These lesions are associated with a good prognosis. One limitation of this report is the lack of preoperative adrenal magnetic resonance imaging of the incidental adrenal mass.

Morphological and Dimensional Analysis of the Nasopalatine Canal: Insights from Cone-Beam Computed Tomography Imaging in a Large Cohort.

BACKGROUND The nasopalatine canal (NPC), or incisive canal, is located in the midline of the palate, posterior to the maxillary central incisors. Its anatomy is important in prosthetic dentistry procedures. This study aimed to assess the anatomical morphology of the NPC according to age, sex, and dental status using cone-beam computed tomography (CBCT) in 335 patients. MATERIAL AND METHODS In this retrospective cross-sectional study, a total of 335 patients were recruited and categorized according to sex, age, and dental status. Individual CBCT images were analyzed in the sagittal, coronal, and axial planes. Also, we recorded the dimensions and morphological shape of the NPC and adjacent buccal bone plate (BBP) under standardized conditions. The associations between sex, age group, NPC shapes and types, and presence of central incisors were assessed. A significance level was set at P<0.05. RESULTS Mean labio-palatal and mediolateral measurements of the incisive foramen were 5.13±1.45 mm and 3.21±0.96 mm, whereas the mean diameter of Stenson foramen was 2.57±1.25 mm, and the total length of the NPC was 11.79±2.50 mm. Funnel, Y, and round-shaped canals were the most prevalent shapes of the NPC in sagittal, coronal, and axial planes. BBP was greater in men, with P=0.011, P=0.000, and P=0.001 at BBP1, BBP2, and BBP3, respectively. CONCLUSIONS NPC and BBP parameter values were slightly higher among male patients. NPC parameters increased with older age. The crest width of BBP decreased with older age and after missing maxillary central incisor teeth.

Unrevealing the multitargeted potency of 3-1-BCMIYPPA against lung cancer structural maintenance and suppression proteins through pharmacokinetics, QM-DFT, and multiscale MD simulation studies.

Lung cancer, a relentless and challenging disease, demands unwavering attention in drug design research. Single-target drugs have yielded limited success, unable to effectively address this malignancy's profound heterogeneity and often developed resistance. Consequently, the clarion call for lung cancer drug design echoes louder than ever, and multitargeted drug design emerges as an imperative approach in this landscape, which is done by concurrently targeting multiple proteins and pathways and offering a beacon of hope. This study is focused on the multitargeted drug designing approach by identifying drug candidates against human cyclin-dependent kinase-2, SRC-2 domains of C-ABL, epidermal growth factor and receptor extracellular domains, and insulin-like growth factor-1 receptor kinase. We performed the multitargeted molecular docking studies of Drug Bank compounds using HTVS, SP and XP algorithms and poses filter with MM\GBSA against all proteins and identified DB02504, namely [3-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1h-Indol-5-Yloxy)-Propyl-]-Phosphonic Acid (3-1-BCMIYPPA) as multitargeted lead with docking and MM\GBSA score range from -8.242 to -6.274 and -28.2 and -44.29 Kcal/mol, respectively. Further, the QikProp-based pharmacokinetic computations and QM-based DFT showed acceptance results against standard values, and interaction fingerprinting reveals that THR, MET, GLY, VAL, LEU, GLU and ASP were among the most interacting residues. The NPT ensemble-based 100ns MD simulation in a neutralised state with an SPC water model has also shown a stable performance and produced deviation and fluctuations <2Å with huge interactions, making it a promising multitargeted drug candidate-however, experimental studies are suggested.

Anomaly detection in multivariate time series data using deep ensemble models.

Anomaly detection in time series data is essential for fraud detection and intrusion monitoring applications. However, it poses challenges due to data complexity and high dimensionality. Industrial applications struggle to process high-dimensional, complex data streams in real time despite existing solutions. This study introduces deep ensemble models to improve traditional time series analysis and anomaly detection methods. Recurrent Neural Networks (RNNs) and Long Short-Term Memory (LSTM) networks effectively handle variable-length sequences and capture long-term relationships. Convolutional Neural Networks (CNNs) are also investigated, especially for univariate or multivariate time series forecasting. The Transformer, an architecture based on Artificial Neural Networks (ANN), has demonstrated promising results in various applications, including time series prediction and anomaly detection. Graph Neural Networks (GNNs) identify time series anomalies by capturing temporal connections and interdependencies between periods, leveraging the underlying graph structure of time series data. A novel feature selection approach is proposed to address challenges posed by high-dimensional data, improving anomaly detection by selecting different or more critical features from the data. This approach outperforms previous techniques in several aspects. Overall, this research introduces state-of-the-art algorithms for anomaly detection in time series data, offering advancements in real-time processing and decision-making across various industrial sectors.

Art or Artifact: Evaluating the Accuracy, Appeal, and Educational Value of AI-Generated Imagery in DALL·E 3 for Illustrating Congenital Heart Diseases.

Artificial Intelligence (AI), particularly AI-Generated Imagery, has the potential to impact medical and patient education. This research explores the use of AI-generated imagery, from text-to-images, in medical education, focusing on congenital heart diseases (CHD). Utilizing ChatGPT's DALL·E 3, the research aims to assess the accuracy and educational value of AI-created images for 20 common CHDs. In this study, we utilized DALL·E 3 to generate a comprehensive set of 110 images, comprising ten images depicting the normal human heart and five images for each of the 20 common CHDs. The generated images were evaluated by a diverse group of 33 healthcare professionals. This cohort included cardiology experts, pediatricians, non-pediatric faculty members, trainees (medical students, interns, pediatric residents), and pediatric nurses. Utilizing a structured framework, these professionals assessed each image for anatomical accuracy, the usefulness of in-picture text, its appeal to medical professionals, and the image's potential applicability in medical presentations. Each item was assessed on a Likert scale of three. The assessments produced a total of 3630 images' assessments. Most AI-generated cardiac images were rated poorly as follows: 80.8% of images were rated as anatomically incorrect or fabricated, 85.2% rated to have incorrect text labels, 78.1% rated as not usable for medical education. The nurses and medical interns were found to have a more positive perception about the AI-generated cardiac images compared to the faculty members, pediatricians, and cardiology experts. Complex congenital anomalies were found to be significantly more predicted to anatomical fabrication compared to simple cardiac anomalies. There were significant challenges identified in image generation. Based on our findings, we recommend a vigilant approach towards the use of AI-generated imagery in medical education at present, underscoring the imperative for thorough validation and the importance of collaboration across disciplines. While we advise against its immediate integration until further validations are conducted, the study advocates for future AI-models to be fine-tuned with accurate medical data, enhancing their reliability and educational utility.

Nanoparticle Augmentation of Adhesive Systems: Impact on Tensile Strength in Fiberglass Post Placement within Root Dentin.

BACKGROUND Modification of the glass fiber post (GFP) with titanium dioxide or silver particles can improve the durability and reliability of dental treatments for ensuring long-term success. This research assessed the tensile bond strength (TBS) of an adhesive system used for cementing GFPs into root dentin following the incorporation of nanoparticles of titanium dioxide (NTiO2) and silver (NAg). MATERIAL AND METHODS Sixty human maxillary canines were prepared to create a 10-mm intra-radicular space for post placement from the cementoenamel junction. The specimens were randomly allocated into 2 groups (a non-thermocycling group and a thermocycling group). Each group was divided into 3 subgroups (10 samples each) according to the adhesive system used (adhesive system devoid of any addition, adhesive system including 1% NAg, and adhesive system infused with 1% NTiO2). TBS tests were conducted and recorded in MPa using a Universal Testing Machine, with an axial load applied at a rate of 0.5 mm/min until failure. The TBS for both groups (non-thermocycling and thermocycling) was measured in megapascals (MPa), and the failure type was recorded. The data were statistically analyzed using one-way analysis of variance (ANOVA) and Tukey's test with P.

An ensemble computational model for prediction of clathrin protein by coupling machine learning with discrete cosine transform.

Clathrin protein (CP) plays a pivotal role in numerous cellular processes, including endocytosis, signal transduction, and neuronal function. Dysregulation of CP has been associated with a spectrum of diseases. Given its involvement in various cellular functions, CP has garnered significant attention for its potential applications in drug design and medicine, ranging from targeted drug delivery to addressing viral infections, neurological disorders, and cancer. The accurate identification of CP is crucial for unraveling its function and devising novel therapeutic strategies. Computational methods offer a rapid, cost-effective, and less labor-intensive alternative to traditional identification methods, making them especially appealing for high-throughput screening. This paper introduces CL-Pred, a novel computational method for CP identification. CL-Pred leverages three feature descriptors: Dipeptide Deviation from Expected Mean (DDE), Bigram Position Specific Scoring Matrix (BiPSSM), and Position Specific Scoring Matrix-Tetra Slice-Discrete Cosine Transform (PSSM-TS-DCT). The model is trained using three classifiers: Support Vector Machine (SVM), Extremely Randomized Tree (ERT), and Light eXtreme Gradient Boosting (LiXGB). Notably, the LiXGB-based model achieves outstanding performance, demonstrating accuracies of 94.63% and 93.65% on the training and testing datasets, respectively. The proposed CL-Pred method is poised to significantly advance our comprehension of clathrin-mediated endocytosis, cellular physiology, and disease pathogenesis. Furthermore, it holds promise for identifying potential drug targets across a spectrum of diseases.Communicated by Ramaswamy H. Sarma.

Retraction: Isolated Superior Mesenteric Artery Dissection After Methamphetamine Use: A Rare Adverse Effect.

[This retracts the article DOI: 10.7759/cureus.19551.].

Online case-based learning for medical students as a teaching method for biochemistry at King Abdulaziz University amid COVID-19 pandemic (a study conducted in 2021).

Online case-based learning (CBL) is a method used by King Abdulaziz University to teach medical students in their preclinical years. The use of CBL in basic sciences is important for enabling medical students to correlate basic sciences with future clinical practice. This study implemented online CBL for biochemistry teaching as part of the medical genetic module for 3rd-year preclinical students. Teaching during the study was completely online because of restricted precautions caused by the COVID-19 pandemic, except for practical sessions that were held on campus. The case was presented to the students involved in prenatal screening and diagnosis. Students were guided to learn and discuss the biochemical tests used for prenatal screening and diagnosis and their clinical importance. They were divided into two groups: the control group was given an online lecture and the intervention group was given an online CBL session before the lecture. The online lecture was given to both groups simultaneously by the same instructor, and then 10 MCQs tests were distributed to both groups after the lecture, and their test scores were compared. A 10-question survey was administered to the intervention group to assess their perception of the online CBL session after the test. A significant difference was found between the intervention and control groups regarding test scores (p < 0.001), and most students found the online CBL session enjoyable and motivating.

The Impact of Non-pharmacological Interventions on Blood Pressure Control in Patients With Hypertension: A Systematic Review.

Hypertension treatment should involve non-pharmacological interventions such as dietary salt restriction, weight loss, exercise, limiting alcohol intake, and dietary approaches to stop hypertension diet. Significant impacts of these interventions have been suggested for a long time. This systematic review aims to assess the influence of non-pharmacological therapies on hypertension patients' ability to control their blood pressure. The review will concentrate on randomized controlled trials examining how non-pharmacological therapies affect blood pressure regulation in hypertension patients. A systematic review was conducted to investigate the impact of non-pharmacological interventions on blood pressure control in patients with hypertension. A comprehensive search for relevant studies was conducted. The following electronic databases were searched: EMBASE, OVID-MEDLINE, and PubMed. The search covered the period between January 2000 and August 2023. The search strategy included a combination of keywords related to hypertension, non-pharmacological interventions, and blood pressure control. A thorough literature evaluation of papers from the EMBASE, OVID-MEDLINE, and PubMed databases was part of the procedure for choosing the studies. Combinations of the keywords telemedicine, primary care, and effectiveness were used for the search. Only studies published in English between January 2000 and August 2023 were included in the search. Through database searching, 862 entries were found, of which 321 were from EMBASE, 112 from OVID-MEDLINE, and 429 from PubMed. After duplicate records were eliminated, 117 records were checked for eligibility. Of these, 100 were disregarded for a variety of reasons, including not relevant to the objectives of the study (n = 63), abstracts or reviews (n = 8), and studies that failed to present interesting research findings (n = 36). The eligibility of the remaining 10 full-text publications was evaluated. Ten articles passed the inclusion tests and were added to the research after a thorough evaluation. Lifestyle modifications are important and have a significant impact on controlling hypertension and a positive impact on reducing blood pressure. Combination therapy is more effective; however, adherence to the modifications is the most important factor affecting the outcomes.

Relationship between Deep Marginal Elevation and Periodontal Parameters: A Systematic Review.

Background and Objectives: This review focuses on reviewing studies from the literature regarding the effects of deep margin elevation on the surrounding periodontium. Materials and Methods: A review of the literature was carried out using the following online databases: Embase, The Cochrane Library, MEDLINE-PubMed and Google Scholar. Our search was limited to articles from 2010 to 2023. The search terms consisted of keywords and MeSH terms, which were 'deep margin elevation', 'coronal margin relocation', 'periodontium' and 'periodontal tissues'. The literature was searched thoroughly by two reviewers. Initially, the titles of the articles were extracted. After removing irrelevant and duplicate articles, abstracts were assessed for relevant articles. Finally, the reviewers analyzed full-text articles. Results: A total of twelve articles, including one randomized clinical trial, three systematic reviews, two prospective cohort, three case series, one a clinical study, one pilot study and one a retrospective study, were selected and analyzed. Conclusions: The review suggests potential benefits of Deep Margin Elevation (DME) over surgical crown lengthening due to reduced invasiveness, yet conclusive effects on periodontal tissue remain unclear, warranting further studies on clinical parameters and inflammatory biomarkers.

Multitargeted inhibitory effect of Mitoxantrone 2HCl on cervical cancer cell cycle regulatory proteins: a multitargeted docking-based MM\GBSA and MD simulation study.

Cervical cancer remains a significant global health concern that starts in the cervix, the lower part of the uterus that connects to the vagina and is caused by the human papillomavirus (HPV), necessitating the development of effective multitargeted effective and resistance-proof therapies. In early-stage cervical cancer may not show any symptoms, however, as the cancer progresses, some people may experience- abnormal vaginal bleeding, watery or bloody vaginal discharge, pain in the pelvis or lower back, pain during sex, and frequent and painful urination. In this study, we screened the complete FDA-approved drug library using a multitargeted inhibitory approach against four cervical cancer proteins, namely mitotic arrest deficient -2, DNA polymerase epsilon B-subunit, benzimidazole-related -1, and threonine-protein kinase-1 which crucially plays its role for the in its development process. We employed the HTVS, SP and XP algorithms for efficient filtering and screening that helped to identify Mitoxantrone 2HCl against all of them with docking and MM\GBSA scores ranging from - 11.63 to - 7.802 kcal/mol and - 74.38 to - 47.73 kcal/mol, respectively. We also evaluated the interaction patterns of each complex and the pharmacokinetics properties that helped gain insight into interactions. Subsequently, we performed multiscale MD simulations for 100 ns to understand the dynamic behaviour and stability of the Mitoxantrone 2HCl -protein complexes that revealed the formation of stable drug-protein complexes and provided insights into the molecular interactions that contribute to Mitoxantrone's inhibitory effects on these proteins and can be a better drug for cervical cancer. However, experimental studies of these findings could pave the way for therapies to combat cervical cancer effectively.

Bloodstream gram-negative bacterial infections in adult patients with leukemia: A retrospective review of medical records in a tertiary care hospital in Western Saudi Arabia.

BACKGROUND: Patients with neutropenic cancers are at high risk of acquiring infections, especially if on chemotherapy. Gram-negative bacterial infections are associated with high mortality. This study aimed to assess clinical characteristics, outcomes, and epidemiology of gram-negative bacterial (GNB) bloodstream infections (BSI) in adult patients with leukemia. METHODS: This single-center, retrospective study included 102 adult patients diagnosed with leukemia between 2017 and 2019. The patients' demographics, infection diagnosis, leukemia diagnosis, comorbidities, and infection outcomes were collected from electronic medical records. RESULTS: The most common GNB were Klebsiella pneumoniae (33.3 %), Pseudomonas aeruginosa (23.5 %), and Escherichia coli (17.6 %). Additionally, 36.7 % of infections were multidrug resistant. The most common comorbidities were cardiovascular diseases (36.7 %), diabetes mellitus (33.3 %), and liver diseases (24.1 %). GNB-infected patients had a higher mortality than noninfected patients (35.3 % and 11.8 %, respectively, p = 0.005). In a multivariable analysis, patients with acute myeloid leukemia and acute lymphoid leukemia were significantly more likely to acquire GNB BSI (p = 0.01), while patients with chronic myelogenous leukemia and chronic lymphocytic leukemia had a lower likelihood of developing GNB BSI. In addition, low hemoglobin level was an independent risk factor of GNB BSI (p = 0.001). Chemotherapeutic agents showed an association with increased risk of GNB BSI. CONCLUSIONS: Patients with acute leukemia and low hemoglobin levels have increased risk of GNB BSI, which was associated with increased mortality. Prospective studies are needed to further assess the effect of co-morbidities and chemotherapy medications on the occurrence of GNB BSI according to the type of leukemia.

The Impact of Frequent Glucose Monitoring on the Prevalence of Complications Among Patients With Diabetes in Saudi Arabia.

BACKGROUND: Diabetes mellitus (DM), including type 1 diabetes (T1D) and type 2 diabetes (T2D), affects the absorption of glucose from the blood. DM has serious complications that can be prevented by adequate knowledge of the disease and its complications, a healthy lifestyle, a modified diet, and regular glucose monitoring. Hence, this study aimed to assess the effects of frequent glucose monitoring on the occurrence of DM complications. METHODS: This cross-sectional study was performed at King Abdulaziz University Hospital between June and December 2022 and included patients with T1D or T2D. After consent, participants who agreed to join filled out an online questionnaire that was used to acquire information, such as demographic data, type of diabetes, blood glucose monitoring, and diabetic complications. RESULTS: A total of 206 diabetic patients participated in this study, with a mean age of 41.2±19.37, with 53.4% having T1D. Most participants monitored their glucose levels (85.4%), and the majority (65.3%) monitored them once or more daily. Patients who monitored their glucose levels more frequently had significantly fewer complications (p = 0.002). Continuous glucose monitoring (CGM) was the best monitoring method, as it demonstrated the lowest rate of complications compared to other methods (p = 0.002). CONCLUSIONS: Frequent glucose monitoring and the use of CGM devices were associated with a decreased number of DM complications. Thus, we recommend that physicians encourage patients to perform CGM as it helps increase the frequency of monitoring.

Feasibility and Efficacy of Low-to-Moderate Intensity Aerobic Exercise Training in Reducing Resting Blood Pressure in Sedentary Older Saudis with Hypertension Living in Social Home Care: A Pilot Randomized Controlled Trial.

Background and Objectives: The effect of non-pharmacological aerobic exercise training on blood pressure in sedentary older individuals receiving social home care in Saudi Arabia has not been investigated. This study aimed to examine the effects of aerobic exercise on blood pressure in sedentary older Saudis with hypertension residing in these settings. Materials and Methods: A pilot randomized control trial was conducted with 27 sedentary individuals, aged 60-85, diagnosed with hypertension, and living in social home care in Makkah, Saudi Arabia. Recruitment took place between November 2020 and January 2021, and participants were randomly assigned to either the experimental or control group. The experimental group engaged in three 45 min sessions of low-to-moderate intensity aerobic activity per week for eight weeks. This trail was registered with the ISRCTN registry (ISRCTN50726324). Results: Following eight weeks of mild to moderate aerobic exercise training, the primary outcome of resting blood pressure showed a significant reduction in the experimental group (systolic blood pressure: mean difference [MD] = 2.91 mmHg, 95% confidence interval [CI] = 1.61, 4.21, p = 0.001; and diastolic blood pressure: MD = 1.33 mmHg, 95% CI = 1.16, 1.50, p = 0.001) compared to the control group. Within the experimental group, there was also a significant decrease in systolic blood pressure (MD = -2.75 mmHg, 95% CI = -7.73, 2.22, p = 0.005) and diastolic blood pressure (MD = -0.83 mmHg, 95% CI = -5.81, 4.14, p = 0.02). Conclusions: This trial demonstrates the feasibility and potential benefits of low-to-moderate intensity aerobic exercise training in reducing resting blood pressure among sedentary older Saudis with hypertension residing in this aged care setting.

Successful surgical removal of a cutaneous lesion compatible with gigantic vascular eccrine spiradenoma: a rare case report.

Giant vascular eccrine spiradenoma (GVES) is an uncommon type of eccrine spiradenoma (ES). Compared to an ES, this is characterized by a greater degree of vascularity and a bigger size overall. In clinical practice, it is frequently mistaken for a vascular or malignant tumor. To achieve an accurate diagnosis of GVES via biopsy and successfully perform the surgical removal of a cutaneous lesion in the left upper abdomen compatible with GVES. We present a 61-year-old female with the lesion accompanied by on-and-off pain, bloody discharge and skin changes surrounding the mass treated surgically. However, there was no fever, weight loss, trauma or family history of malignancy or cancer managed by surgical excision. The patient recovered well postoperatively and was discharged on the same day with a 2-week follow-up. The wound got healed, the clips were removed on Day 7 postoperatively, and there was no requirement for further follow-up.

Intranasal Delivery of a Silymarin Loaded Microemulsion for the Effective Treatment of Parkinson's Disease in Rats: Formulation, Optimization, Characterization, and In Vivo Evaluation.

A mucoadhesive microemulsion of lipophilic silymarin (SLMMME) was developed to treat Parkinson's disease (PD). Optimization of the SLM microemulsion (ME) was performed using Central Composite Design (CCD). The composition of oil, surfactant, co-surfactant, and water was varied, as per the design, to optimize their ratio and achieve desirable droplet size, zeta potential, and drug loading. The droplet size, zeta potential, and drug loading of optimized SLMME were 61.26 ± 3.65 nm, -24.26 ± 0.2 mV, and 97.28 ± 4.87%, respectively. With the addition of chitosan, the droplet size and zeta potential of the developed ME were both improved considerably. In vitro cell toxicity investigations on a neuroblastoma cell line confirmed that SLMMME was non-toxic and harmless. In comparison to ME and drug solution, mucoadhesive ME had the most flow through sheep nasal mucosa. Further, the in vitro release showed significantly higher drug release, and diffusion of the SLM loaded in MEs than that of the silymarin solution (SLMS). The assessment of behavioral and biochemical parameters, as well as inflammatory markers, showed significant (p < 0.05) amelioration in their level, confirming the significant improvement in neuroprotection in rats treated with SLMMME compared to rats treated with naïve SLM.

Aloe-emodin exhibits growth-suppressive effects on androgen-independent human prostate cancer DU145 cells via inhibiting the Wnt/ß-catenin signaling pathway: an in vitro and in silico study.

At the molecular level, several developmental signaling pathways, such as Wnt/ß-catenin, have been associated with the initiation and subsequent progression of prostate carcinomas. The present report elucidated the anti-cancerous attributes of an anthraquinone, aloe-emodin (AE), against androgen-independent human prostate cancer DU145 cells. The cytotoxicity profiling of AE showed that it exerted significant cytotoxic effects and increased lactose dehydrogenase levels in DU145 cells (p < 0.01 and p < 0.001). AE also induced considerable reactive oxygen species (ROS)-mediated oxidative stress, which escalated at higher AE concentrations of 20 and 25 µM. AE also efficiently instigated nuclear fragmentation and condensation concomitantly, followed by the activation of caspase-3 and -9 within DU145 cells. AE further reduced the viability of mitochondria with increased cytosolic cytochrome-c levels (p < 0.01 and p < 0.001) in DU145 cells. Importantly, AE exposure was also correlated with reduced Wnt2 and ß-catenin mRNA levels along with their target genes, including cyclin D1 and c-myc. Furthermore, the molecular mechanism of AE was evaluated by performing molecular docking studies with Wnt2 and ß-catenin. Evidently, AE exhibited good binding energy scores toward Wnt2 and ß-catenin comparable with their respective standards, CCT036477 (Wnt2 inhibitor) and FH535 (ß-catenin inhibitor). Thus, it may be considered that AE was competent in exerting anti-growth effects against DU145 androgen-independent prostate cancer cells plausibly by modulating the expression of Wnt/ß-catenin signaling.

Influence of Surface Type with Coffee Immersion on Surface Topography and Optical and Mechanical Properties of Selected Ceramic Materials.

BACKGROUND The aim of this study was to assess and compare the effect of surface type (glazed or polished) with coffee immersion and aging on surface topography (Ra), optical properties (TP, OP), and mechanical properties (fracture forces and modes) of zirconia-reinforced lithium silicate (Vita Suprinity), hybrid polymer-infiltrated-feldspathic ceramic network material (Vita Enamic), and leucite-containing feldspathic glass (Vitablocs® Mark II) made by computer-aided design and computer-aided manufactured (CAD/CAM) ceramic materials. MATERIAL AND METHODS Fifty-four specimens were assembled out of the above 3 CAD/CAMs ceramic materials. Each group was divided into glazed or polished surfaces, having 9 specimens of every type and stained in coffee for 15 days. Ra and color of specimens in the form of TP and OP were recorded before and after immersion in staining material. Fracture forces and modes were analyzed after the 90-day aging. Data were analyzed using ANOVA, then post hoc analysis and Bonferroni tests. RESULTS Our study found significant differences in Ra, TP, and Op before and after coffee immersion between glazed and polished specimens, with higher values in the polished surfaces among the 3 ceramic materials. The highest values of fracture resistance were noted in Vita Suprinity, and Vita Enamic had the lowest values, without significant differences among groups. CONCLUSIONS Most of the TP and OP values were in acceptable clinical range, and Vita Suprinity had superior TP than the other groups. Reparable fracture types were observed in Vita Suprinity, whereas semi-reparable and non-reparable were predominant in other groups.