A Dual Therapeutic Approach to Diabetes Mellitus via Bioactive Phytochemicals Found in a Poly Herbal Extract by Restoration of Favorable Gut Flora and Related Short-Chain Fatty Acids.

Diabetes mellitus (DM), a metabolic and endocrine condition, poses a serious threat to human health and longevity. The emerging role of gut microbiome associated with bioactive compounds has recently created a new hope for DM treatment. UHPLC-HRMS methods were used to identify these compounds in a poly herbal ethanolic extract (PHE). The effects of PHE on body weight (BW), fasting blood glucose (FBG) level, gut microbiota, fecal short-chain fatty acids (SCFAs) production, and the correlation between DM-related indices and gut microbes, in rats were investigated. Chebulic acid (0.368%), gallic acid (0.469%), andrographolide (1.304%), berberine (6.442%), and numerous polysaccharides were the most representative constituents in PHE. A more significant BW gain and a reduction in FBG level towards normal of PHE 600 mg/kg treated rats group were resulted at the end of 28th days of the study. Moreover, the composition of the gut microbiota corroborated the study's hypothesis, as evidenced by an increased ratio of Bacteroidetes to Firmicutes and some beneficial microbial species, including Prevotella copri and Lactobacillus hamster. The relative abundance of Bifidobacterium pseudolongum, Ruminococcus bromii, and Blautia producta was found to decline in PHE treatment groups as compared to diabetic group. The abundance of beneficial bacteria in PHE 600 mg/kg treatment group was concurrently associated with increased SCFAs concentrations of acetate and propionate (7.26 nmol/g and 4.13 nmol/g). The findings of this study suggest a promising approach to prevent DM by demonstrating that these naturally occurring compounds decreased FBG levels by increasing SCFAs content and SCFAs producing gut microbiota.

Radiation-induced Undifferentiated Malignant Pituitary Tumor After 5 Years of Treatment for Cushing Disease.

The occurrence of a second neoplasm possibly constitutes an adverse and uncommon complication after radiotherapy. The incidence of a second pituitary tumor in patients irradiated for adrenocorticotropic hormone secreting pituitary adenoma is rare. We report a case of a 40-year-old female with Cushing disease who underwent surgical management followed by radiotherapy. After 5 years of initial treatment, an increase in tumor size was evident at the same location, with a significant interval growth of the parasellar component of the lesion. Histology revealed an undifferentiated highly malignant sarcoma. In the span of next 2 years, the patient was followed with 2 repeat decompression surgeries and radiotherapy because of significant recurrent compressive symptoms by locally invasive malignant tumor. Despite the best efforts, the patient remained unresponsive to multiple treatment strategies (eg, surgical resections and radiotherapy) and succumbed to death.

Complete-arch implant-supported fixed dental prostheses fabricated with PEEK and PEKK framework: a systematic review.

PURPOSE: To evaluate the performance of complete-arch implant-supported fixed dental prostheses (FDPs) fabricated with polyetheretherketone (PEEK) and polyetherketoneketone (PEKK) framework in clinical cases. MATERIALS AND METHODS: This systematic review followed the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses and was registered in the International Prospective Register of Systematic Reviews with the number CRD42023399494. The electronic database PubMed, Cochrane Library and EBSCOhost were assessed for clinical research and reports on complete-arch implant-supported FDPs fabricated with PEEK and PEKK framework. Human studies with a minimum follow-up of 1 year and published in an English language were the only ones included. RESULTS: The initial database and hand search provided 564 articles. Finally, 12 articles published between 2018 and 2022 were included in this systematic review. The mean follow-up ranged from 1 year to 6 years. The included studies reported 119 (114 PEEK, 5 PEKK) complete-arch implant-supported FDPs during 1 year follow-up. The cumulative survival rate of prostheses with PEEK as a framework was 97.3%. Prostheses fractures and complications were found with both PEEK and PEKK frameworks. No implant failure reported with both PEEK and PEKK prostheses. CONCLUSION: In short-term follow-up, the complete-arch implant-supported FDPs with PEEK as a framework showed a good survival rate and acceptable health of the supporting tissues. The PEEK framework had shown adhesion issues as the most common prosthetic complication. Limited data were available on PEKK as framework material, so further long-term clinical trials are required.

EGFR targeted albumin nanoparticles of oleanolic acid: In silico screening of nanocarrier, cytotoxicity and pharmacokinetics for lung cancer therapy.

This study aimed to develop cetuximab (CTX) functionalized albumin nanoparticles (ALB-NPs) of oleanolic acid for EGFR targeted lung cancer therapy. The molecular docking methodology has been applied for a selection of suitable nanocarrier. Various physicochemical parameters like particle size, polydispersity, zeta potential, morphology, entrapment efficiency, and in-vitro drug release of all the ALB-NPs were analyzed. Furthermore, the in-vitro qualitative and quantitative cellular uptake study revealed that higher uptake of CTX conjugated ALB-NPs than nontargeted ALB-NPs in A549 cells. The in-vitro MTT assay revealed that the IC50 value of CTX-OLA-ALB-NPs (4.34 ± 1.90 µg/mL) was significantly reduced (p < 0.001) than OLA-ALB-NPs (13.87 ± 1.28 µg/mL) in A-549 cells. CTX-OLA-ALB-NPs caused apoptosis in A-549 cells at concentrations equivalent to its IC50 value and blocked the cell cycle in the G0/G1 phases. The hemocompatibility, histopathology and lung safety study confirmed the biocompatibility of the developed NPs. In vivo ultrasound and photoacoustic imaging confirmed the targeted delivery of the NPs to lung cancer. The findings demonstrated that CTX-OLA-ALB-NPs have potential for site-specific delivery of OLA for effective and targeted therapy of lung carcinoma.

Dapagliflozin for inpatient hyperglycemia in cardiac surgery patients with type 2 diabetes: randomised controlled trial (Dapa-Hospital trial).

AIMS: To examine the efficacy and safety of dapagliflozin in the treatment of hyperglycemia in cardiac surgery patients with type 2 diabetes (T2D). METHODS: Cardiac surgery patients with T2D (n = 250) were randomly assigned (1:1) to receive dapagliflozin plus basal-bolus insulin (DAPA group) or basal-bolus insulin alone (INSULIN group) in the early postoperative period. The primary outcome was mean difference in daily blood glucose (BG) concentrations between groups. The major safety outcomes were the occurrence of severe ketonemia/diabetic ketoacidosis (DKA) and hypoglycemia. All analyses were performed according to the intention-to-treat principle. RESULTS: The median age of the patients was 61 years (range, 55-61), and 219 (87.6%) were men. Overall, the randomization blood glucose was 165 mg/dL (SD, 37) and glycated hemoglobin was 7.7% (SD, 1.4). There were no differences in mean daily BG concentrations (149 vs. 150 mg/dL), mean percentage of readings within target BG of 70-180 mg/dL (82.7% vs. 82.5%), total daily insulin dose (mean, 39 vs. 40 units/day), number of daily insulin injections (median, 3.9 vs. 4), length of hospital stay (median, 10 vs. 10 days), or hospital complications (21.6% vs. 24.8%) between the DAPA and INSULIN groups. The mean plasma ketone levels were significantly higher in the DAPA group than in the INSULIN group at day 3 (0.71 vs. 0.30 mmol/L) and day 5 (0.42 vs. 0.19 mmol/L) of randomization. Six patients in the DAPA group developed severe ketonemia, but no patient developed DKA. There were no differences in the proportion of patients with BG < 70 mg/dL (9.6% vs. 7.2%) between the two groups. CONCLUSION: Dapagliflozin complementary to basal-bolus insulin does not improve glycemia further over and above the basal-bolus insulin alone in hospitalized cardiac surgery patients. Dapagliflozin significantly increases plasma ketones levels. Safety of dapagliflozin in hospitalized patients needs further investigation. Trial registration ClinicalTrials.gov NCT05457933.

Do antihypertensive medications have an effect on dental implants? A systematic review.

PURPOSE: The purpose of this systematic review was to compare the clinical outcomes of dental implants in users of antihypertensive medication with those of nonusers. METHODS: This systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and was registered in the International Prospective Register of Systematic Reviews under the number CRD42022319336. The electronic databases Medline (PubMed) and Central Cochrane were searched for relevant scientific literature published in English through May 2022. The focused question was, "Do patients taking antihypertensive medications have a similar impact on the clinical outcome and survival of dental implants compared with nonusers?". RESULTS: A total of 49 articles were found, of which 3 articles were finally selected for a qualitative synthesis. The three studies included 959 patients. In all three studies, the commonly used medication was renin-angiotensin system (RAS) inhibitors. Two studies mentioned implant survival rate, which was 99.4% in antihypertensive medication users and 96.1% in the nonusers. One study found a higher implant stability quotient (ISQ) in patients taking antihypertensive medication (75.7 ± 5.9) compared with patients not taking antihypertensive medication (73.7 ± 8.1). CONCLUSIONS: The limited available evidence showed that patient taking antihypertensive medications had comparable success rate and implant stability to patients not taking medications. The studies included patients taking different antihypertensive medications, so a drug-specific conclusion regarding the clinical outcome of dental implants is not possible. Further studies are needed, including patients taking certain antihypertensive medications, to determine their effects on dental implants.

Extraction, isolation, synthesis, and biological evaluation of novel piperic acid derivatives for the treatment of Alzheimer's disease.

In this paper, we developed a series of piperic acid (PA) analogs with the aim of overcoming the limitations associated with the natural products for the management of Alzheimer's disease (AD). A comprehensive SAR study was performed to enhance cholinesterase inhibition of PA. The acetylcholinesterase inhibition and its kinetic data suggested 6j as the lead molecule (AChE IC50 = 2.13 ± 0.015 µM, BChE = 28.19 ± 0.20%), in comparison to PA (AChE = 7.14 ± 0.98%) which was further selected for various biological studies in AD models. 6j, exhibited interaction with the peripheral anionic site of AChE, BBB permeability (Pe = 7.98), and antioxidant property (% radical scavenging activity = 35.41 ± 1.09, 2.43 ± 1.65, for 6j and PA at 20 M[Formula: see text], respectively). The result from the metal chelation study suggests that 6j did not effectively chelate iron. The molecular modeling studies suggested that 6j could effectively interact with Ser293, Phe295, Arg296, and Tyr34 of AChE. In the cell-based cytotoxicity studies, 6j exhibited cytocompatibility at the different tested concentrations. The acute toxicity data on mice suggested that compound 6j had no renal and hepatotoxicity at 500 mg/kg. Moreover, 6j could effectively reverse scopolamine-induced amnesia by improving spatial and cognitive memory in mice. The above results strongly suggest that compound 6j may act as a novel multi-targeted lead for AD therapy.

Network pharmacology of apigeniflavan: a novel bioactive compound of Trema orientalis Linn. in the treatment of pancreatic cancer through bioinformatics approaches.

Pancreatic cancer is the seventh most prevalent cause of mortality globally. Since time immemorial, plant-derived products have been in use as therapeutic agents due to the existence of biologically active molecules called secondary metabolites. Flavonoids obtained from plants participate in cell cycle arrest, induce autophagy and apoptosis, and decrease oxidative stress in pancreatic cancer. The present study involves network pharmacology-based study of the methanolic leaf extract of Trema orientalis (MLETO) Linn. From the high-resolution mass spectrometry (HRMS) analysis, 21 nucleated flavonoids were screened out, of which only apigeniflavan was selected for further studies because it followed Lipinski's rule and showed no toxicity. The pharmacokinetics and physiochemical characteristics of apigeniflavan were performed using the online web servers pkCSM, Swiss ADME, and ProTox-II. This is the first in silico study to report the efficiency of apigeniflavan in pancreatic cancer treatment. The targets of apigeniflavan were fetched from SwissTargetPrediction database. The targets of pancreatic cancer were retrieved from DisGeNET and GeneCards. The protein-protein interaction of the common genes using Cytoscape yielded the top five hub genes: KDR, VEGFA, AKT1, SRC, and ESR1. Upon molecular docking, the lowest binding energies corresponded to best docking score which indicated the highest protein-ligand affinity. Kyoto Encyclopaedia of Genes and Genomes (KEGG) database was employed to see the involvement of hub genes in pathways related to pancreatic cancer. The following, pancreatic cancer pathway, MAPK, VEGF, PI3K-Akt, and ErbB signaling pathways, were found to be significant. Our results indicate the involvement of the hub genes in tumor growth, invasion and proliferation in the above-mentioned pathways, and therefore necessitating their downregulation. Moreover, apigeniflavan can flourish as a promising drug for the treatment of pancreatic cancer in future.

A comparative study to evaluate the heat generated during osteotomy with conventional drill, trephine and alveolar expander.

Purpose: Excessively produced heat could lead to clinical failure of osseointegration. This study was done to compare the heat generated during osteotomy with the conventional drill, trephine, and alveolar expander . Materials and methods: This in vitro study was performed on ten bovine femoral bones. In each femoral bone, three osteotomy sites were prepared at a distance of 1.5cm using the conventional drill, trephine, and alveolar expander. During osteotomy, the site was irrigated with a copius amount of normal saline. Osteotomy sites of 3.6 mm in diameter and 11.5 mm in length were prepared using the conventional drill and bone trephines. The alveolar expander used for preparing the osteotomy site was 3.5mm, the nearest dimensions available. The temperature rise was measured using a thermocouple thermometer. Repeated measures ANOVA and Fisher's least significant difference pairwise comparison test was done for statistical analysis. Results: Repeated measures ANOVA revealed a significant difference in the heat generation with the conventional drill, trephine, and alveolar expander (p<0.001). The mean heat generated was maximum with the trephine (28.26±0.246 0C) followed by the conventional drill (27.27±0.297 0C) and least with alveolar expander (25.64±0.142 0C). Pairwise comparison showed a significant difference in heat generated during osteotomy with conventional drill compared to trephine (P=0.023), conventional drill compared to alveolar expander (P=0.014), and trephine compared to alveolar expander (P<0.001). Conclusion: The heat generated with trephine was maximum compared to the alveolar expander and conventional drills. If in case trephine is to be used, both internal and external irrigation must be used. Less heat generation during osteotomy by alveolar expander seems very promising and advantageous for better osseointegration.

Network pharmacology-based anti-pancreatic cancer potential of kaempferol and catechin of Trema orientalis L. through computational approach.

In pancreatic cancer, healthy cells in the pancreas begin to malfunction and proliferate out of control. According to our conventional knowledge, many plants contain several novel bioactive compounds, having pharmaceutical applications for the treatment of disease like pancreatic cancer. The methanolic fraction of fruit extract of Trema orientalis L. (MFETO) was analysed through HRMS. In this in silico study, pharmacokinetic and physicochemical properties of the identified flavonoids from MFETO were screened out by ADMET analysis. Kaempferol and catechin followed Lipinski rules and showed no toxicity in Protox II. Targets of these compounds were taken from SwissTarget prediction and TCMSP whilst targets for pancreatic cancer were taken from GeneCards and DisGeNET databases. The protein-protein interaction (PPI) network of common genes was generated through STRING and then exported to the Cytoscape to get top 5 hub genes (AKT1, SRC, EGFR, TNF, and CASP3). The interaction between compounds and hub genes was analysed using molecular docking, and high binding affinity between them can be visualised by Biovia discovery studio visualizer. Our study shows that, five hub genes related to pancreatic cancer play an important role in tumour growth induction, invasion and migration. Kaempferol effectively check cell migration by inhibiting ERK1/2, EGFR-related SRC, and AKT pathways by scavenging ROS whilst catechin inhibited TNFα-induced activation and cell cycle arrest at G1 and G2/M phases by induction of apoptosis of malignant cells. Kaempferol and catechin containing MFETO can be used for formulation of potent drugs for pancreatic cancer treatment in future.

Marginal Gap and Internal Fit of Fixed Dental Prostheses Fabricated Using Intraoral vs Extraoral Scanning: A Systematic Review and Meta-analysis.

PURPOSE: To compare the marginal gap and internal fit of fixed dental prostheses (FDPs) fabricated using intraoral vs extraoral scanning methods. MATERIALS AND METHODS: MEDLINE/PubMed and the Cochrane database were searched. The focused PICO question was: For the fabrication of FDPs, does an intraoral scanning technique result in a different marginal gap than an extraoral scanning technique? The secondary outcome assessed was internal fit. Studies were selected based on the inclusion criteria, and a meta-analysis was performed. RESULTS: A total of 14 studies (10 in vitro and 4 in vivo) were included in the meta-analysis. Marginal gap in single crowns was evaluated in 5 studies, copings for single crowns in 5 studies, three-unit FDPs in 3 studies, and both single-crown and three-unit FDPs in 1 study. Significantly lower marginal gap was found with intraoral scanning compared to impression scanning (P < .001) and cast scanning (P < .001), and for impression scanning compared to cast scanning (P = .037). Internal fit was superior with intraoral scanning compared to impression scanning, and this difference was significant (P < .001). No significant differences were found in internal fit with cast scanning compared to intraoral or impression scanning. The mean marginal gap/internal fit was 188.3 µm/146.2 µm with intraoral scanning, 116.29 µm/168.2 µm with impression scanning, and 195.1 µm/229.1 µm with cast scanning. CONCLUSION: Marginal gap was lower with intraoral scanning than with impression scanning and cast scanning. Impression scanning showed less marginal gap than cast scanning. Internal fit with intraoral scanning was superior to impression scanning, but when compared to cast scanning, no difference was found.

A review article on neuroprotective, immunomodulatory, and anti-inflammatory role of vitamin-D3 in elderly COVID-19 patients.

Vitamin D3 is a secosteroid, broad-spectrum immunomodulatory, antioxidant, and anti-inflammatory hormone produced either by the internal subcutaneous pathway in the presence of ultraviolet B (UVB) rays or by the external pathway in the form of supplements. Vitamin D3 deficiency is a common and reversible contributor to mortality and morbidity among critically ill patients, including Coronavirus Disease 2019 (COVID-19) and other viral infections. The major functions of vitamin D3 are inhibiting the proinflammatory pathways, including nuclear factor kappa B (NF-kB), inflammatory cytokines, such as interleukin-6 (ILs-6), interleukin-18 (ILs-18), and tumour necrosis factor (TNF), preventing the loss of neural sensation in COVID-19, maintaining respiratory homeostasis, and acting as an antiviral, antimalarial, and antihypertensive agent. Vitamin D3 has an important role in reversing the COVID-19 infection in patients who have previously suffered from a neurological disease, such as Alzheimer's disease, Parkinson disease, motor neuron disease, multiple sclerosis, Creutzfeldt-Jakob disease, stroke, cardiovascular problems, headache, sleep-associated disorder, and others. Moreover, vitamin D3 plays a key role in regulating the gene expression of different pro-inflammatory cytokines. In addition to the information provided above, the current review article provides the most recent information on Vitamin D against COVID-19 with comorbid neurological disorders. Furthermore, we present the most recent advancement and molecular mechanism of action of vitamin D3. Diabetes, cardiovascular disease, and neurological disorders are comorbid conditions, and vitamin D3 is a critical regulator of COVID-19 infection during these conditions. In the midst of the COVID-19 epidemic, factors such as sex, latitudes, nutrition, demography, pollution, and gut microbiota warrants for additional research on vitamin D supplements.

Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention.

Alpha-lipoic acid is an organic, sulfate-based compound produced by plants, humans, and animals. As a potent antioxidant and a natural dithiol compound, it performs a crucial role in mitochondrial bioenergetic reactions. A healthy human body, on the other hand, can synthesize enough α-lipoic acid to scavenge reactive oxygen species and increase endogenous antioxidants; however, the amount of α-lipoic acid inside the body decreases significantly with age, resulting in endothelial dysfunction. Molecular orbital energy and spin density analysis indicate that the sulfhydryl (-SH) group of molecules has the greatest electron donating activity, which would be responsible for the antioxidant potential and free radical scavenging activity. α-Lipoic acid acts as a chelating agent for metal ions, a quenching agent for reactive oxygen species, and a reducing agent for the oxidized form of glutathione and vitamins C and E. α-Lipoic acid enantiomers and its reduced form have antioxidant, cognitive, cardiovascular, detoxifying, anti-aging, dietary supplement, anti-cancer, neuroprotective, antimicrobial, and anti-inflammatory properties. α-Lipoic acid has cytotoxic and antiproliferative effects on several cancers, including polycystic ovarian syndrome. It also has usefulness in the context of female and male infertility. Although α-lipoic acid has numerous clinical applications, the majority of them stem from its antioxidant properties; however, its bioavailability in its pure form is low (approximately 30%). However, nanoformulations have shown promise in this regard. The proton affinity and electron donating activity, as a redox-active agent, would be responsible for the antioxidant potential and free radical scavenging activity of the molecule. This review discusses the most recent clinical data on α-lipoic acid in the prevention, management, and treatment of a variety of diseases, including coronavirus disease 2019. Based on current evidence, the preclinical and clinical potential of this molecule is discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s43450-023-00370-1.

Phytochemicals, Antioxidant, Anti-inflammatory Studies, and Identification of Bioactive Compounds Using GC-MS of Ethanolic Novel Polyherbal Extract.

Hyperglycemia is the hallmark of diabetes, which is a collection of related metabolic disorders. Over time, diabetes can cause a variety of problems, including cardiovascular disease, nephropathy, neuropathy, and retinopathy. Ethanolic novel polyherbal extract (PHE) was prepared by mixing equal amounts of the following ingredients: Terminalia chebula Retz. (TC), Terminalia bellerica Roxb. (TB), Berberis aristata DC. (BA), Nyctanthes arbostratis L. (NA), Premna integrifolia L. (PI), and Andrographis paniculata Nees. (AP). Analysis of PHE results revealed phytochemicals like glycosides, flavonoids, alkaloids, tannins, phytosterols, and saponins. The aim of the study was to prepare an ethanolic extract of PHE using the cold maceration technique, and identify bioactive molecules from gas chromatography-mass spectrometry (GC-MS) analysis, and evaluate biological responses by using in vitro studies like antioxidant and anti-inflammatory activity. PHE was found to contain a total of 35 phytochemicals in GC-MS of which 22 bioactive compounds were obtained in good proportion. There are a few new ones, including 2-buten-1-ol, 2-ethyl-4-(2, 2, 3-trimethyl-3-cyclopenten-1-yl (17.22%), 1, 2, 5, 6-tetrahydrobenzonitrile (4.26%), 4-piperidinamine, 2, 2, 6, 6-tetramethyl-(0.07%), undecanoic acid, 5-chloro-, chloromethyl ester (0.41%), are identified. Antioxidant activity was estimated using EC50 values of 392.143 µg/ml, which were comparable to the standard value of EC50 310.513 µg/ml obtained using DPPH. Antioxidant activity was estimated with EC50 392.143 µg/ml, comparable to standard EC50 310.513 µg/ml using DPPH. In vitro anti-inflammatory potential was found with IC50 of 91.449 µg/ml, comparable to standard IC50 89.451 µg/ml for membrane stabilization and IC50 of 36.940 µg/ml, comparable to standard IC50 35.723 µg/ml for protein denaturation assays. As a result, the findings of this study show an enrichment of bioactive phytochemicals that can be used to investigate biological activity. To better understand how diabetes receptors work, in silico studies like docking could be carried out.

Patient satisfaction and crestal bone changes with one-piece and two-piece single implant-retained mandibular overdenture: A randomized controlled clinical study.

PURPOSE: The present study was done to assess patient satisfaction and crestal bone changes with one-piece and two-piece single implant-retained mandibular overdentures (SIMOs). METHODS: The participants included in Group 1 (n=12) received one-piece SIMOs; the participants in Group 2 (n=12) received two-piece SIMOs.Scheduled follow-ups were done at 1 month and 1 year after implant placement. Patient satisfaction and crestal bone changes were evaluated. The data obtained were analyzed statistically with independent Student t-test. RESULTS: Visual analogue scale (VAS) score for patient satisfaction with one-piece and two-piece SIMOs were statistically significant at 1-year of follow-up. The patient satisfaction level on the VAS score increased (38.1 to 51.1) with group one-piece SIMOs and two-piece SIMOs (36.6 to 46.8) at baseline to 1 month (P=0.13). The patient satisfaction level increased (38.1 to 56.6) with group one-piece SIMOs and two-piece SIMOs (36.6 to 52.2) at baseline to 1 year (P=0.03). At the 1 year follow-ups, group 1 had mean crestal bone loss of 0.80 ± 0.49 mm and group 2 had 1.24 ± 0.90 mm (P=0.16). Crestal bone loss was greater in the two-piece SIMOs group at 1 month and 1 year follow-ups, but statistically it was insignificant. CONCLUSIONS: One-piece SIMOs seemed to be a viable treatment option with increased patient satisfaction on a VAS. Crestal bone loss was greater in the patients with two-piece SIMOs during follow-up. One-piece SIMOs was comparatively simple with less invasive procedures and needed fewer components,so considerable number of patients requiring implant retained dentures could be benefited.

Efficacy and safety of degludec U100 versus glargine U300 for the early postoperative management of patients with type 2 diabetes mellitus undergoing coronary artery bypass graft surgery: A non-inferiority randomized trial.

AIMS: To compare the efficacy and safety of degludec U100 versus glargine U300 for the early postoperative management of patients with type 2 diabetes mellitus (T2D) undergoing coronary artery bypass graft (CABG) surgery. METHODS: A total of 239 patients were randomly assigned (1:1) to receive a basal-bolus regimen in the early postoperative period using degludec U100 (n = 122) or glargine U300 (n = 117) as basal and glulisine before meals. The primary outcome was mean differences between groups in their daily BG concentrations. The major safety outcome was the occurrence of hypoglycemia. RESULTS: There were no differences in mean daily BG concentrations (157 vs. 162 mg/dl), mean percentage of readings within target BG of 70-180 mg/dl (74% vs. 73%), daily basal insulin dose (19 vs. 21 units/day), length of stay (median [IQR]: 9 vs. 9 days), or hospital complications (21.3% vs. 21.4%) between treatment groups. There were no differences in the proportion of patients with BG <70 mg/dl (15.6% vs. 23.1%) or <54 mg/dl (1.6% vs. 4.3%) between degludec-100 and glargine-300 groups. CONCLUSIONS: Treatment with degludec U100 is as effective and safe as glargine U300 for the early postoperative hospital management of patients with T2D undergoing CABG.

Intranasally Co-administered Berberine and Curcumin Loaded in Transfersomal Vesicles Improved Inhibition of Amyloid Formation and BACE-1.

Selective permeability of the blood-brain barrier restricts the treatment efficacy of neurologic diseases. Berberine (BBR) and curcumin (CUR)-loaded transferosomes (TRANS) were prepared for the effective management of Alzheimer's disease (AD). The study involved the syntheses of BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS by the film hydration method. Vesicles were characterized to ensure the formation of drug-loaded vesicles and their in vivo performance. The particle sizes of BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS were 139.2 ± 7, 143.4 ± 8, and 165.3 ± 6.5 nm, respectively. The presence of diffused rings in the SED image indicates the crystalline nature of the payload. Low surface roughness in an AFM image could be associated with the presence of a surface lipid. BBR-CUR-TRANS showed 41.03 ± 1.22 and 47.79 ± 3.67% release of BBR and 19.22 ± 1.47 and 24.67 ± 1.94% release of CUR, respectively, in phosphate buffer saline (pH 7.4) and acetate buffer (pH 4.0). Formulations showed sustained release of both loaded drugs. BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS exhibited a lower percentage of hemolysis than pure BBR and CUR, indicating the safety of the payload from delivery vesicles. Lower percentages of binding were recorded from BBR-CUR-TRANS than BBR-TRANS and CUR-TRANS. Acetylcholinesterase inhibition activity of the prepared transferosomes was greater than that of pure drugs, which are thought to have good cellular penetration. The spatial memory was improved in treated mice models. The level of malondialdehyde decreased in AD animals treated with BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS, respectively, as compared to the scopolamine-induced AD animals. BBR-CUR-TRANS-treated animals showed the highest decrease in the NO level. The catalase level was significantly restored in scopolamine-intoxicated animals treated with BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS. The immunohistochemistry result suggested that the BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS have significantly decreased the regulation of expression of BACE-1 through antioxidant activity. In conclusion, the study highlights the utility of formulated transferosomes as promising carriers for the co-delivery of drugs to the brain.

Evaluation of customized cobalt-chromium abutments fabricated with different manufacturing process versus titanium stock abutments on the marginal misfit -An in vitro study.

Aim: Accurate fit of the abutment to the implant is required for the uniform load distribution throughout the assembly. The study aims to compare the marginal misfit of titanium stock abutments with the cobalt-chromium (CoCr) customized abutments fabricated with the different manufacturing processes in internal hex implant-abutment connection using an appropriate scanning technique. Setting and Design: In vitro comparative study. Materials and Methods: A total of 40 abutments were included in the study. Ten titanium stock abutments were used as control (Group CN) and 30 CoCr abutments were fabricated and taken as the test group. Stock abutments were scanned and from obtained images test group abutments were fabricated as follows: Ten cast abutments (Group CA), 10 sintered abutments (Group SA), and 10 milled abutments (Group MA). Endosseous implanst having internal hex connections were matched with 10 stock abutments and 30 customized CoCr abutments. Implants were mounted in a clear epoxy resin block and the abutments were then fitted onto the implants with a torque of 30Ncm. The marginal discrepancy at implant-abutment connections was measured with confocal laser scanning microscope. Statistical Analysis Used: One-way ANOVA and Tukey's post hoc test was done for statistical analysis. Results: One-way ANOVA revealed a significant difference in marginal misfit of abutments. The mean marginal misfit was lowest for stock abutments (0.35 ± 0.009 µm). Among the customized abutments, the mean marginal misfit was highest for cast abutments (2.44 ± 0.445 µm) followed by sintered abutments (1.67 ± 0.232 µm) and least for milled abutments (0.65 ± 0.041 µm). A significant difference was found in marginal misfit with cast abutments and sintered abutments when compared to stock abutments (P < 0.001). The difference in marginal misfit was insignificant between stock abutments and milled abutments (P = 0.052). Conclusion: Difference in marginal misfit exists between the titanium stock abutments and customized CoCr abutments. Among the customized abutments, milled CoCr abutments have the least marginal discrepancy and cast CoCr abutments have a maximum marginal discrepancy. Milled CoCr abutments can be used as an alternative to titanium stock abutments.

Efficient Catalytic Degradation of Selected Toxic Dyes by Green Biosynthesized Silver Nanoparticles Using Aqueous Leaf Extract of Cestrum nocturnum L.

In the present study, the catalytic degradation of selected toxic dyes (methylene blue, 4-nitrophenol, 4-nitroaniline, and congo red) using biosynthesized green silver nanoparticles (AgNPs) of Cestrum nocturnum L. was successfully performed. These AgNPs are efficiently synthesized when a reaction mixture containing 5 mL of aqueous extract (3%) and 100 mL of silver nitrate (1 mM) is exposed under sunlight for 5 min. The synthesis of AgNPs was confirmed based on the change in the color of the reaction mixture from pale yellow to dark brown, with maximum absorbance at 455 nm. Obtained NPs were characterized by different techniques, i.e., FTIR, XRD, HR-TEM, HR-SEM, SAED, XRD, EDX, AFM, and DLS. Green synthesized AgNPs were nearly mono-dispersed, smooth, spherical, and crystalline in nature. The average size of the maximum number of AgNPs was 77.28 ± 2.801 nm. The reduction of dyes using a good reducing agent (NaBH4) was tested. A fast catalytic degradation of dyes took place within a short period of time when AgNPs were added in the reaction mixture in the presence of NaBH4. As a final recommendation, Cestrum nocturnum aqueous leaf extract-mediated AgNPs could be effectively implemented for environmental rehabilitation because of their exceptional performance. This can be utilized in the treatment of industrial wastewater through the breakdown of hazardous dyes.