Dimensional stability of 3D-printed edentulous and fully dentate hollowed maxillary models over periods of time.

BACKGROUND: Dental casts made utilising digital workflow are becoming more common because to their speed and cost savings. However, studies on their dimensional accuracy over time with diverse designs are missing. OBJECTIVE: The aim of this in vitro study was to assess the dimensional stability of 3D-printed edentulous and fully dentate hollowed maxillary models with 50-micrometer resolution over 1 day, 14 days, and 28 days using surface matching software. METHODS: Scanned edentulous and fully dentate maxillary typodont models were used as references. The models were scanned by a desktop lab scanner of 15-micrometer accuracy (D900, 3Shape). Then, the files were used in designing software (Meshmixer, Autodesk) to create hollowed maxillary casts. Fifteen edentulous and 15 fully dentate (total of 30) models were printed using a DLP lab printer (Cara print 4.0, Kulzer). The 3D-printed models were scanned using the same desktop lab scanner of 15-micrometer accuracy at intervals of baseline days, 1 day, 14 days, and 28 days to assess the effect of aging (n = 120). The dimensional changes were quantified and compared using the root mean square (RMS) method, expressed in micrometres (µm). The study employed repeated measures analysis of variance (ANOVA) to assess and compare the root mean square (RMS) values across the variables. The data was analysed using SPSS (26, Chicago, Illinois, USA). RESULTS: The RMS of the edentulous models rapidly increased from a mean value of 0.257 at the beginning of the study to 0.384 after twenty-eight days. However, the mean RMS values for the dentate models did not change much over the four intervals. It varied only from 0.355 to 0.347. The mean values for edentulous patients increased from 0.014 to 0.029 during the period from baseline to twenty-eight days. However, the mean average values decreased for the dentate models from 0.033 to 0.014 during this period. By utilizing ANOVA, mean RMS values increased insignificantly till one day but significantly to fourteen and twenty-eight days. Dentate model mean values differed insignificantly across four intervals. Repeated measures ANOVA for combined and separated data showed no significant differences across edentulous, dentate, and total models over times. CONCLUSION: The study revealed changes in the dimensions of 3D-printed edentulous models over a span of 3 and 4 weeks. Caution should be applied when using 3D-printed dental master models for constructing definitive prostheses on edentulous models over a period of 3 to 4 weeks.

Application of 32 factorial design for loratadine-loaded nanosponge in topical gel formulation: comprehensive in-vitro and ex vivo evaluations.

Loratadine (LoR) is a highly lipophilic and practically insoluble in water, hence having a low oral bioavailability. As it is formulated as topical gel, it competitively binds with the receptors, thus reducing the side-effects. The objective of this study was to prepare LoR loaded nanosponge (LoR-NS) in gel for topical delivery. Nine different formulations of emulsion were prepared by solvent evaporation method with polyvinyl alcohol (PVA), ethyl cellulose (EC), and dichloromethane (DCM). Based on 32 Full Factorial Design (FFD), optimization was carried out by varying the concentration of LOR:EC ratio and stirring rate. The preparations were subjected for the evaluation of particle size (PS), in vitro release, zeta potential (ZP) and entrapment efficiency (EE). The results revealed that the NS dispersion was nanosized with sustained release profiles and significant PS. The optimised formulation was formulated and incorporated into carbopol 934P hydrogel. The formulation was then examined to surface morphological characterizations using scanning electron microscopy (SEM) which depicted spherical NS. Stability studies, undertaken for 2 months at 40 ± 2 °C/75 ± 5% RH, concluded to the stability of the formulation. The formulation did not cause skin irritation. Therefore, the prepared NS hydrogel proved to be a promising applicant for LoR as a novel drug delivery system (NDDS) for safe, sustained and controlled topical application.

Laparo-Endoscopic Single-Site Left Donor Nephrectomy In Patients With Uncommon Renal Vascular Anatomy: Does the Technique Make a Difference?

BACKGROUND: To compare donor and recipient outcomes in patients with renal artery and ante-aortic renal vein vs unusual renal vascular anatomy undergoing laparoendoscopic single-site donor nephrectomy (LESSDN). METHODS: A retrospective chart review of the comparative study of donor and recipient outcomes of LESSDN in donors with venous abnormality (n = 28, group A), arterial abnormality (n = 74, group B), and standard donors (n = 248, group C). RESULTS: From September 2016 to August 2022, 350 left LESSDN were performed. The most common anomalies in group A were the retro-aortic and 2 renal veins in 12 patients each. In group B, 72 and 2 patients had 2 and 3 renal arteries, respectively. Operative and warm ischemia times were significantly longer in donors with vascular anomalies. Moreover, patient creatinine on discharge was significantly higher in arterial anomalies; it was 1.61 ± 0.22 compared with 1.26 ± 0.43 and 1.25 ± 0.32 mg/dL for patients with no anomalies and venous anomalies, respectively (P < .001). However, serum creatinine levels recovered after 1 month and were comparable between the study groups. Recipients, operative time, and vascular anastomosis time were significantly longer in recipients with vascular anomaly. Slow graft function was higher in group B (6.9%) than in the other groups. One-year graft survival rates were 96.4%, 94.6%, and 97.1% (P = .496). CONCLUSION: With increased experience, LESSDN in multiple renal arteries and uncommon venous anatomy cases is feasible and safe. Moreover, it does not influence donor or recipient outcomes.

Knowledge, Attitude, and Practices Related to Foot Care Among Diabetic Patients in Tabuk City, Saudi Arabia.

Introduction Diabetic foot ulcer (DFU) is a prevalent complication of diabetes mellitus (DM), affecting approximately 15% of all diabetic patients. This condition poses significant challenges due to its association with major morbidity, mortality, high costs, and diminished quality of life. The incidence of diabetic foot complications among diagnosed diabetes cases is alarming, making it a primary concern in diabetes management. Diabetes mellitus, a chronic metabolic disorder, impacts nearly every system in the body. Methods In this study, a cross-sectional design was employed to assess the level of knowledge, attitude, and practices related to foot care among 432 diabetic patients in Tabuk City, Saudi Arabia. Results The participants' ages ranged from 18 to above 60 years, with (n = 206, 47.69%) being male and (n = 226, 52.31%) female. Type 2 diabetes was prevalent, constituting (n = 277, 64.12%) of cases, whereas (n = 187, 38.29%) had type 1 diabetes. Approximately (n= 224, 51.9%) of patients had been diagnosed with diabetes for less than 10 years. A significant portion (n= 302, 69.91%) of patients did not report any foot complaints. However, (n= 88, 20.37%) had a history of healed ulcers, and (n= 21, 4.9%) had undergone amputation due to diabetes. The majority of patients (n = 228, 52.78%) were under oral agent treatment. Conclusion The study population demonstrated adequate knowledge about diabetes management and exhibited positive attitudes toward diabetes and its related complications, particularly concerning foot care. While most patients displayed appropriate practices related to diabetic foot care, some participants showed inadequate adherence to essential procedures. Addressing these gaps in knowledge and practices is crucial for enhancing the overall management of diabetic foot complications among patients.

Association of Oral and General Health with Nutritional Status of Older Adults Attending Two Medical Centers in Riyadh, Saudi Arabia: A Cross-Sectional Study.

Malnutrition could profoundly affect older adults' oral health and quality of life, whereas oral health might, in turn, impact dietary intake and nutritional status. The present study aimed to investigate the association between general and oral health and nutritional status among older adults attending nutrition clinics at two main medical centers in Riyadh, Saudi Arabia. A cross-section study was carried out among adult patients (≥60 years) who attended a geriatric clinic or nutrition clinic at King Khalid University Hospital or King Abdulaziz Medical City, Riyadh. A validated clinician's Mini Nutritional Assessment Short-Form (MNA-SF), Oral Health Impact Profile-5 (OHIP-5), and 36-Item Short Form Survey (SF-36) were collected from each participant. A total of 261 participants with a mean age of 72.14 (±8.97) years were recruited. Diabetes (71%) and hypertension (80%) were present in the majority of patients. The overall MNA-SF score was (10 ± 3). Based on the categorization of the MNA-SF score, 65.9% were classified as malnourished or at risk of malnutrition. Participants with OHIP-5 scores higher than the median (>5) were more likely to be malnourished than those with scores at or lower than 5 (p < 0). The adjusted odd ratio for the MNA-SF score categories indicated that for a one-unit increase in the total SF-36 score, the odds of the malnourished category are 0.94 times less than the risk of malnutrition and normal nutritional status, with OR 0.97 (95% CI 0.94-0.95). Malnutrition or being at risk of malnutrition is likely associated with poor general and oral health. Healthcare providers need to incorporate dietitians into care plans to promote the nutritional health of older adults.

Unveiling Nature's potential: Promising natural compounds in Parkinson's disease management.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Although the exact etiology of PD remains elusive, growing evidence suggests a complex interplay of genetic, environmental, and lifestyle factors in its development. Despite advances in pharmacological interventions, current treatments primarily focus on managing symptoms rather than altering the disease's underlying course. In recent years, natural phytocompounds have emerged as a promising avenue for PD management. Phytochemicals derived from plants, such as phenolic acids, flavones, phenols, flavonoids, polyphenols, saponins, terpenes, alkaloids, and amino acids, have been extensively studied for their potential neuroprotective effects. These bioactive compounds possess a wide range of therapeutic properties, including antioxidant, anti-inflammatory, anti-apoptotic, and anti-aggregation activities, which may counteract the neurodegenerative processes in PD. This comprehensive review delves into the pathophysiology of PD, with a specific focus on the roles of oxidative stress, mitochondrial dysfunction, and protein malfunction in disease pathogenesis. The review collates a wealth of evidence from preclinical studies and in vitro experiments, highlighting the potential of various phytochemicals in attenuating dopaminergic neuron degeneration, reducing α-synuclein aggregation, and modulating neuroinflammatory responses. Prominent among the natural compounds studied are curcumin, resveratrol, coenzyme Q10, and omega-3 fatty acids, which have demonstrated neuroprotective effects in experimental models of PD. Additionally, flavonoids like baicalein, luteolin, quercetin, and nobiletin, and alkaloids such as berberine and physostigmine, show promise in mitigating PD-associated pathologies. This review emphasizes the need for further research through controlled clinical trials to establish the safety and efficacy of these natural compounds in PD management. Although preclinical evidence is compelling, the translation of these findings into effective therapies for PD necessitates robust clinical investigation. Rigorous evaluation of pharmacokinetics, bioavailability, and potential drug interactions is imperative to pave the way for evidence-based treatment strategies. With the rising interest in natural alternatives and the potential for synergistic effects with conventional therapies, this review serves as a comprehensive resource for pharmaceutical industries, researchers, and clinicians seeking novel therapeutic approaches to combat PD. Harnessing the therapeutic potential of these natural phytocompounds may hold the key to improving the quality of life for PD patients and moving towards disease-modifying therapies in the future.

Metformin HCl-loaded transethosomal gel; development, characterization, and antidiabetic potential evaluation in the diabetes-induced rat model.

Herein we designed, optimized, and characterized the Metformin Hydrochloride Transethosomes (MTF-TES) and incorporate them into Chitosan gel to develop Metformin Hydrochloride loaded Transethosomal gel (MTF-TES gel) that provides a sustained release, improved transdermal flux and improved antidiabetic response of MTF. Design Expert® software (Ver. 12, Stat-Ease, USA) was applied for the statistical optimization of MTF-TES. The formulation with Mean Particle Size Distribution (MPSD) of 165.4 ± 2.3 nm, Zeta Potential (ZP) of -21.2 ± 1.9 mV, Polydispersity Index (PDI) of 0.169 ± 0.033, and MTF percent Entrapment Efficiency (%EE) of 89.76 ± 4.12 was considered to be optimized. To check the chemical incompatibility among the MTF and other formulation components, Fourier Transform Infrared (FTIR) spectroscopy was performed and demonstrated with no chemical interaction. Surface morphology, uniformity, and segregation were evaluated through Transmission Electron Microscopy (TEM). It was revealed that the nanoparticles were spherical and round in form with intact borders. The fabricated MTF-TES has shown sustained release followed by a more pronounced effect in MTF-TES gel as compared to the plain MTF solution (MTFS) at a pH of 7.4. The MTF-TES has shown enhanced permeation followed by MTF-TES gel as compared to the MTFS at a pH of 7.4. In vivo antidiabetic assay was performed and results have shown improved antidiabetic potential of the MTF-TES gel, in contrast to MTF-gel. Conclusively, MTF-TES is a promising anti-diabetic candidate for transdermal drug delivery that can provide sustained MTF release and enhanced antidiabetic effect.

Trastuzumab-Mediated Cardiotoxicity and Its Preventive Intervention by Zingerone through Antioxidant and Inflammatory Pathway in Rats.

Trastuzumab (TZB) is a new medicine, used to treat cancers of the breast and stomach. However, the cardiotoxic potential of this drug edges out its clinical advantages. The present study was designed to find out the effect of zingerone against trastuzumab-mediated cardiotoxicity in rats. In this study, five groups of rats with eight animals in each group were used. Group 1 was treated with normal saline, as a normal control (NC); Group 2 was treated with TZB (6 mg/kg/week-for five weeks) intraperitoneally as a toxic control. Groups 3 and 4 were pre-treated with zingerone (50 and 100 mg/kg, as per their body weight orally) along with five doses of TZB for five weeks, and Group 5 was treated with zingerone (100 mg/kg, body weight orally) as a control. TZB treatment showed cardiotoxicity as evidenced by increased levels of aspartate aminotransferase (AST), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and lipid peroxidation (LPO) and decreased level of glutathione (GSH), and antioxidant enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s- transferase (GST), catalase (CAT), and superoxide dismutase (SOD) activities. Zingerone pre-treatment significantly decreased the levels of AST, CK-MB, LDH, and LPO and increased GSH and antioxidant enzymes content toward their normal level. In the TZB-alone administered group, inflammatory cytokines (IL-2 and TNF-α) levels were also elevated. Pre-treatment with zingerone restored the level of IL-2 and TNF-α toward normal level. The current findings undoubtedly demonstrated zingerone's cardioprotective nature against TZB-mediated cardiotoxicity in rats with the evidence of histopathological recall.

An Insight into Codon Pattern Analysis of Autophagy Genes Associated with Virus Infection.

INTRODUCTION: Apoptosis and autophagy are the two fundamental processes involved in maintaining homeostasis, and a common stimulus may initiate the processes. Autophagy has been implicated in various diseases, including viral infections. Genetic manipulations leading to altered gene expression might be a strategy to check virus infection. AIM: Determination of molecular patterns, relative synonymous codon usage, codon preference, codon bias, codon pair bias, and rare codons so that genetic manipulation of autophagy genes may be done to curb viral infection. METHODS: Using various software, algorithms, and statistical analysis, insights into codon patterns were obtained. A total of 41 autophagy genes were envisaged as they are involved in virus infection. RESULTS: The A/T and G/C ending codons are preferred by different genes. AAA-GAA and CAG-CTG codon pairs are the most abundant codon pairs. CGA, TCG, CCG, and GCG are rarely used codons. CONCLUSION: The information generated in the present study helps manipulate the gene expression level of virus infection-associated autophagy genes through gene modification tools like CRISPR. Codon deoptimization for reducing while codon pair optimization for enhancing is efficacious for HO-1 gene expression.

Therapeutic Potential of Capsaicin against Cyclophosphamide-Induced Liver Damage.

Cyclophosphamide (CPM) is a classical alkylating agent used in different cancer chemotherapy regimens and is restricted due to severe adverse effects, including hepatotoxicity. Natural or plant-derived antioxidants such as capsaicin were utilized in this study to examine the hepatoprotective benefits against cyclophosphamide-induced hepatotoxicity. The rats were divided into five groups: a normal control group, a toxic group (CPM), an intraperitoneal injection of a single dose of 200 mg/kg b.w. on the fourth day, a pretreated group with two doses of CPS (10 mg and 20 mg/kg b.w.) orally for six consecutive days, and an intraperitoneal administration of 200 mg/kg b.w. on the fourth day of treatment. The fifth group was administered with the highest dose of CPS (20 mg/kg b.w.) orally for six consecutive days. After 24 h of administration of CPS, the rats were anesthetized, blood was collected, and the serum enzyme toxicity was evaluated. After the blood sampling and euthanasia of all the animals, the liver was isolated for further toxicity and histopathological examination. The results revealed that serum liver markers (AST, ALT, ALP, BLI) significantly increased after CPM administration, but were subsequently restored after CPS treatment with both doses. In addition, lipid peroxidation (MDA), inflammatory cytokines (IL-1ß, TNF-α), and apoptotic markers (Caspase-3) increased, and antioxidant enzymes (GSH, CAT, SOD) were significantly decreased after CPM administration, and it was re-established by CPS treatment. However, CPS effectively protected against the CPM-induced histopathological architects of liver tissues. In conclusion, CPS attenuates CPM-induced hepatotoxicity via modulating oxidative stress, apoptotic signals, and cytokine pathway. Therefore, CPS could play a significant role as a supplement during the chemotherapy of patients.

Strong Selectional Forces Fine-Tune CpG Content in Genes Involved in Neurological Disorders as Revealed by Codon Usage Patterns.

Neurodegenerative disorders cause irreversible damage to the neurons and adversely affect the quality of life. Protein misfolding and their aggregation in specific parts of the brain, mitochondrial dysfunction, calcium load, proteolytic stress, and oxidative stress are among the causes of neurodegenerative disorders. In addition, altered metabolism has been associated with neurodegeneration as evidenced by reductions in glutamine and alanine in transient global amnesia patients, higher homocysteine-cysteine disulfide, and lower methionine decline in serum urea have been observed in Alzheimer's disease patients. Neurodegeneration thus appears to be a culmination of altered metabolism. The study's objective is to analyze various attributes like composition, physical properties of the protein, and factors like selectional and mutational forces, influencing codon usage preferences in a panel of genes involved directly or indirectly in metabolism and contributing to neurodegeneration. Various parameters, including gene composition, dinucleotide analysis, Relative synonymous codon usage (RSCU), Codon adaptation index (CAI), neutrality and parity plots, and different protein indices, were computed and analyzed to determine the codon usage pattern and factors affecting it. The correlation of intrinsic protein properties such as the grand average of hydropathicity index (GRAVY), isoelectric point, hydrophobicity, and acidic, basic, and neutral amino acid content has been found to influence codon usage. In genes up to 800 amino acids long, the GC3 content was highly variable, while GC12 content was relatively constant. An optimum CpG content is present in genes to maintain a high expression level as required for genes involved in metabolism. Also observed was a low codon usage bias with a higher protein expression level. Compositional parameters and nucleotides at the second position of codons played essential roles in explaining the extent of bias. Overall analysis indicated that the dominance of selection pressure and compositional constraints and mutational forces shape codon usage.

Habits, Traditions, and Beliefs Associated With the Use of Complementary and Alternative Medicine Among Diabetic Patients in Al-Qassim Region, Saudi Arabia.

Background Since diabetes mellitus (DM) affects every aspect of a person's being, more and more people are using complementary and alternative therapies such as ingesting ginger and cinnamon in addition to conventional medical care and lifestyle changes to manage their condition and enhance their well-being. Although this population uses complementary and alternative medicine (CAM) at a high rate, it is unclear what causes this use. Objective We aim to know the habits, traditions, and beliefs associated with the use of complementary and alternative medicine among type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) patients in the Al-Qassim region of Saudi Arabia. Methods This is an observational cross-sectional study conducted among diabetes patients in Al-Qassim, Saudi Arabia, in 2022. Participants were selected via a non-probability sampling technique. Patients were interviewed in the diabetic clinics using validated questionnaires. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) software (IBM SPSS Statistics, Armonk, NY, USA). Results A total of 444 validated responses were received in this study. The average age was 50 ± 16.9 years, and females represented the highest proportion (58.6%). Moreover, we found that most of the participants had type 2 diabetes (79.1%) and 93 (20.9%) had type 1 diabetes. Hypertension was the most reported chronic disease. Our results revealed that the prevalence of CAM usage was 29.1%. Regarding the sources of information on herbal medicines, we found that more than half of the respondents (57.4%) obtained information from friends, relatives, and neighbors. Ginger, vitamins and minerals, and cinnamon were the most frequently used herbals among our participants. Our results found that 38% of CAM users used herbal products on a regular basis. As regards the frequency of using herbal products, 29.5% of the respondents used herbal medicine weekly and 21.7% used it daily. In addition, we found that gender, marital status, and monthly income were significantly associated with the use of CAM (P value = 0.008, 0.011, and 0.011, respectively). The significantly higher CAM use was associated with females, married participants, and participants with a monthly income of 10,000-15,000 Saudi riyal (SAR). Conclusion According to our research, CAM use among diabetes patients in the Al-Qassim region was found to be relatively common. The prevalence of type 2 diabetes mellitus was higher (79.1%) in comparison to type 1 diabetes mellitus (20.9%). Also, the most commonly used herb was ginger (47.66%), followed by vitamins and minerals (44.53%), and cinnamon (42.19%). Patients with diabetes need to be informed of the significance of telling their doctors about their use of CAM.

Functional evidence for biased inhibition of G protein signaling by YM-254890 in human coronary artery endothelial cells.

Small molecular chemicals targeting individual subtype of G proteins including Gs, Gi/o and Gq has been lacking, except for pertussis toxin being an established selective peptide inhibitor of the Gi/o protein. Recently, a cyclic depsipeptide compound YM-254890 isolated from culture broth of Chromobacterium sp. was reported as a selective inhibitor for the Gq protein by blocking GDP exchange of GTP on the α subunit of Gq complex. However, functional selectivity of YM-254890 towards various G proteins was not fully characterized, primarily due to its restricted availability before 2017. Here, using human coronary artery endothelial cells as a model, we performed a systemic pharmacological evaluation on the functional selectivity of YM-254890 on multiple G protein-mediated receptor signaling. First, we confirmed that YM-254890, at 30 nM, abolished UTP-activated P2Y2 receptor-mediated Ca2+ signaling and ERK1/2 phosphorylation, indicating its potent inhibition on the Gq protein. However, we unexpectedly found that YM-254890 also significantly suppressed cAMP elevation and ERK1/2 phosphorylation induced by multiple Gs-coupled receptors including ß2-adrenegic, adenosine A2 and PGI2 receptors. Surprisingly, although YM-254890 had no impact on CXCR4/Gi/o protein-mediated suppression of cAMP production, it abolished ERK1/2 activation. Further, no cellular toxicity was observed for YM-254890, and it neither affected A23187- or thapsigargin-induced Ca2+ signaling, nor forskolin-induced cAMP elevation and growth factor-induced MAPK signaling. We conclude that YM-254890 is not a selective inhibitor for Gq protein; instead, it acts as a broad-spectrum inhibitor for Gq and Gs proteins and exhibits a biased inhibition on Gi/o signaling, without affecting non-GPCR-mediated cellular signaling.