Addressing the challenges of complex type III odontoid fractures: Clinical and radiological outcomes of various treatment modalities.

Background: Unlike simple fractures, complex Type III odontoid fractures-characterized by intricate morphology and pathomechanics-pose significant management challenges. This study aims to evaluate the clinical and radiological outcomes of conservative and surgical treatment modalities for these complex fractures, with a focus on assessing factors influencing fracture union. Methods: Following approval of our institutional review board, this retrospective observational cohort study was conducted. All Patients with complex Type III odontoid fractures who were managed at our center from June 2016 to December 2022 were assessed for eligibility. The primary outcome was union status. Secondary outcomes included the ASIA impairment scale, neck disability index (NDI), and complications. Logistic regression analysis was conducted to identify risk factors for adverse union outcomes. Results: A total of 39 patients were included in the final analysis, with a mean age of 36.10 years. Nine patients were managed conservatively, 12 patients underwent anterior odontoid screw (AOS) fixation, and 18 patients received posterior fusion (PF). The rate of bony union varied significantly across the treatment groups, 100 % in the PF group, 58 % in the AOS group and 22 % in the conservative group (p = 0.0012). The NDI revealed superior functional outcomes in the PF group compared to the other groups (p = 0.0436). Failure of primary treatment was observed in seven patients (three from the conservative group and four from the AOS), necessitating secondary treatment with PF. Lateral mass gap >2 mm, coronal tilt >5°, and atlantoaxial instability >50 % were identified as significant risk factors for adverse union outcomes. Conclusions: Surgical treatment, particularly PF, offers superior outcomes in terms of union rates and functional recovery for complex Type III odontoid fractures. The identification of specific radiological measurements as significant risk factors for non-union underscores the need for detailed imaging and careful patient selection for conservative versus surgical management.

RuC nanosheet as a promising biosensing material for detecting the aromatic amino acids: a DFT study.

Density functional theory (DFT) calculations were performed to examine the potential of the RuC nanosheet as a biosensor towards the aromatic amino acids (AAA; tryptophan (TRP), histidine (HIS), tyrosine (TYR), and phenylalanine (PHE)). The AAA molecules were placed vertically and horizontally with respect to the RuC surface and then subjected to geometrical relaxation. According to the geometry relaxation results, it was found that all AAA molecules preferred to be adsorbed on the RuC surface in a horizontal configuration rather than a vertical one, except the HIS molecule, which desired to be vertically adsorbed on the RuC nanosheet. From the energy manifestations, the adsorption process within the TRP⋯RuC complexes had the greatest desired negative adsorption energy (E ads), followed by HIS⋯, TYR⋯, and then PHE⋯RuC complexes (E ads = -40.22, -36.54, -23.95, and -16.62 kcal mol-1, respectively). As indicated by the FMO data, changes in the E HOMO, E LUMO, and E gap values of the RuC nanosheet following the adsorption process demonstrated the capacity of the RuC nanosheet to adsorb the AAA molecules. The outcomes of Bader charge transfer revealed that the RuC nanosheet had the ability to donate electrons to the AAA molecules during the adsorption process, supported by the positive Q t values. Consistent with the E ads conclusions, the TRP⋯RuC complexes had the largest Q t values, indicating the potential affinity of the RuC nanosheet to adsorb the TRP molecule. Following the adsorption of AAA molecules on the RuC nanosheet, new peaks and bands were discovered based on the DOS and the band structure plots, respectively, revealing the validity of the adsorption process. Additionally, the current adsorption findings on the RuC nanosheet were compared to those on the graphene (GN) nanosheet. The outcomes of the comparison demonstrated the outperformance of the RuC nanosheet over the GN nanosheet in adsorbing the AAA molecules. These outcomes provide a solid foundation for further research on the RuC nanosheets to detect small biomolecules.

Exploring marine natural products for identifying putative candidates as EBNA1 inhibitors: An insight from molecular docking, molecular dynamics, and DFT computations.

Epstein-Barr virus (EBV), namely a DNA neoplasm virus, is liable for over 1 % of malignant neoplasms involving Hodgkin's and Burkitt's lymphoma as well as ventral cancer. Despite the crucial role of EBV in carcinoma evolution, no treatment has been discovered yet against EBV. Epstein-Barr nuclear antigen 1 (EBNA1), the EBV-encoded latent protein, is produced in all EBV-linked neoplasms and is the only latent protein in these cancer types. EBNA1 protein has multiple roles in the upkeep, reproduction, and EBV genome separation and can thus act as an attractive therapeutic target for treating EBV-related malignancies. In the past few decades, attempts have been made to develop specialized EBNA1 inhibitors to reduce EBNA1 expression or obstruct EBNA1-relied processes, but none has been approved yet. Marine natural products (MNPs) have garnered significant interest as potential sources of antiviral drug candidates. In seeking potent drug candidates to inhibit EBV reproduction, an MNP database containing >14,000 compounds was mined to hunt putative EBNA1 inhibitors using docking computations and molecular dynamics simulations (MDS). On the basis of binding energy (ΔGbinding) estimations over 200 ns MDS, UMHMNP351444649 and UMHMNP134128179 revealed a greater binding affinity towards EBNA1 compared to KWG, with ΔGbinding values of -35.6, -33.3, and -32.4 kcal/mol, respectively. Structural and energetical investigations of UMHMNP351444649 and UMHMNP134128179 complexed with EBNA1 were inspected, unveiling the great constancy of these inhibitors within the EBNA1 binding site. Moreover, the identified MNPs demonstrated favorable physicochemical and medicinal chemistry characteristics. Finally, density functional theory calculations were executed, and the results assured the outcomes obtained from docking computations and MDS. These findings proposed UMHMNP351444649 and UMHMNP134128179 as potential anti-EBV drug candidates that warrant further in-vitro and in-vivo assays.

New sesquiterpenes from the soft coral Litophyton arboreum.

Two new sesquiterpenes; 8α,11-dihydroxy-ß-cyperon (2), and 5-epi-7α-hydroxy-( +)-oplopanone (3), were isolated from the soft coral Litophyton arboreum, together with nine known ones, including five sesquiterpenes; 11-hydroxy-8-oxo-ß-cyperon (1), alismoxide (4), 5ß,8ß-epidioxy-11-hydroxy-6-eudesmene (5), chabrolidione B (6), 7-oxo-tri-nor-eudesm-5-en-4ß-ol (7), two sterols; 7ß-acetoxy-24-methyl-cholesta-5,24(28)-diene-3ß,19-diol (8), nebrosteroid M (9), and two glycerol derivatives; chimyl alcohol (10) and batyl alcohol (11). The structures of the isolated compounds were characterized using spectroscopic techniques, predominately HR-ESI-MS, 1D, 2D-NMR, and ECD analyses. Compounds 1-11 were evaluated for their cytotoxic activity against three human cancer-cell lines (A549, MCF-7 and HepG2), and anti-leishmanial potential against the causal parasite, Leishmania major. Compounds 4, 8, and 9 exhibited potent cytotoxic activity against the A549 cell line (IC50 = 17.0 ± 2.5, 13.5 ± 2.1, and 16.5 ± 1.3 µg/ml, respectively) as compared with the standard antitumor agent etoposide (IC50 28.4 ± 4.5 µg/ml). In addition, compound 9 exhibited remarkable cytotoxic activity against MCF-7 cell line (IC50 = 24.7 ± 2.1 µg/ml: 22.2 ± 4.2 µg/mL for etoposide).

The cytotoxic activities of the major diterpene extracted from Salvia multicaulis (Bardakosh) are mediated by the regulation of heat-shock response and fatty acid metabolism pathways in human leukemia cells.

BACKGROUND: Leukemia is one of the most lethal cancers worldwide and represents the sixth-leading cause of cancer deaths. The results of leukemia treatment have not been as positive as desired, and recurrence is common. PURPOSE: Thus, there is an urgent requirement for the development of new therapeutic drugs. Salvia multicaulis (Bardakosh) is a widespread species that contains multiple phytochemical components with anti-cancer activities. METHODS: We isolated and characterized the major diterpene candesalvone B methyl ester from S. multicaulis and investigated its action as a cytotoxic agent towards sensitive and drug-resistant leukemia cells by the resazurin reduction assay. Additionally, the targeted genes and the affected molecular mechanisms attributed to the potent cytotoxic activities were discovered by transcriptome-wide mRNA expression profiling. The targets predicted to be regulated by candesalvone B methyl ester in each cell line were confirmed by qRT-PCR, molecular docking, microscale thermophoresis, and western blotting. Moreover, cell cycle distribution and apoptosis were analyzed by flow cytometry. RESULTS: Candesalvone B methyl ester was cytotoxic with IC50 values of 20.95 ± 0.15 µM against CCRF-CEM cells and 4.13 ± 0.10 µM against multidrug-resistant CEM/ADR5000 leukemia cells. The pathway enrichment analysis disclosed that candesalvone B methyl ester could regulate the heat-shock response signaling pathway via targeting heat shock factor 1 (HSF1) in CCRF-CEM cells and ELOVL fatty acid elongase 5 (ELOVL5) controls the fatty acid metabolism pathway in CEM/ADR5000 cells. Microscale thermophoresis showed the binding of candesalvone B methyl ester with HSF1 and ELOVL5, confirming the results of molecular docking analysis. Down-regulation of both HSF1 and ELOVL5 by candesalvone B methyl ester as detected by both western blotting and RT-qPCR was related to the reversal of drug resistance in the leukemia cells. Furthermore, candesalvone B methyl ester increased the arrest in the sub-G1 phase of the cell cycle in a dose-dependent manner from 1.3 % to 32.3 % with concomitant induction of apoptosis up to 29.0 % in CCRF-CEM leukemic cells upon inhibition of HSF1. CONCLUSION: Candesalvone B methyl ester isolated from S. multicaulis exerted cytotoxicity by affecting apoptosis, cell division, and modulation of expression levels of genes contributing to the heat stress signaling and fatty acid metabolism pathways that could relieve drug resistance of leukemia cells.

Efficacy of Anti-Thyroid Medications in Patients with Graves' Disease.

INTRODUCTION: Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism due to increased thyroid-stimulating hormone receptor antibodies (TRAb).The treatment of GD often consists of radioactive iodine therapy, anti-thyroid drugs (ATD), or thyroidectomy. Since few studies have collected data on remission rates after treatment with ATD in Saudi Arabia, our study aimed to assess the efficacy and the clinical predictors of GD long-term remission with ATD use. METHOD: We conducted a retrospective chart review study of 189 patients with GD treated with ATD between July 2015 and December 2022 at the endocrine clinics in King Abdulaziz Medical City in Riyadh. All GD patients, adults, and adolescents aged 14 years and older who were treated with ATD during the study period and had at least 18 months of follow-up were included in the study. Patients with insufficient follow-up and those who underwent radioactive iodine (RAI) therapy or thyroidectomy as first-line therapy for GD were excluded from the study. RESULTS: The study sample consisted of 189 patients, 72% of whom were female. The patients' median age was 38years (33, 49). A total of 103 patients (54.5%) achieved remission. The median follow-up period for the patients was 22.0 months (9, 36). Patients who achieved remission had lower mean free T4 levels (25.8pmol/l ± 8.93 versus 28.8pmol/l ± 10.82) (P value = 0.038) and lower median TRAb titer (5.1IU/l (2.9, 10.7)) versus (10.5IU/l (4.2, 22.5)) (P value = 0.001) than patients who did not achieve remission. Thirty-five out of 103 patients who achieved remission (34%) relapsed after ATD discontinuation. The patients who relapsed showed higher median thyroid uptake on 99mTc-pertechnetate scan than patients who did not relapse: 10.3% (5.19, 16.81) versus 6.0% (3.09, 12.38), with a P value of 0.03. They also received ATD for a longer period, 40.0 months (29.00, 58.00) versus 25.0 months (19.00, 32.50), with a P value of < 0.0001. CONCLUSION: The remission of GD was achieved in approximately half of the patients treated with ATD; however, approximately one-third of them relapsed. Lower Free T4 and TRAb levels at diagnosis were associated with remission. Longer ATD use and higher thyroid uptake upon diagnosis were associated with relapse after ATD discontinuation. Future studies are necessary to ascertain the predictors of ATD success in patients with GD.

Unconventional Radical and Radical-Hole Site-Based Interactions in Halogen-Bearing Dimers and Trimers: A Comparative Study.

Radical (R•) and R•-hole site-based interactions are comparatively studied, for the first time, using ab initio methods. In this regard, R•-bearing molecules •XO3 (where X = Cl, Br, and I) were subjected to direct interaction with NH3 within dimeric and trimeric forms in the form of NH3···â€¢XO3/•XO3···NH3 and NH3···â€¢XO3···NH3 complexes, respectively. As confirmed by electrostatic potential analysis, the studied R•-bearing molecules •XO3 had the outstanding potentiality to interact as Lewis acid centers via two positive sites dubbed as R• and R•-hole sites. Such an observation proposed the potentiality of the considered •XO3 molecules to engage in unconventional R• and well-established R•-hole site-based interactions with Lewis bases. This was confirmed by negative interaction (E int) energies, ranging from -4.93 to -19.89 kcal/mol, with higher favorability for R• site-based interactions over the R•-hole site-based ones. MP2 energetic features furnished higher preferability for the R• site-based interactions than the R•-hole site-based ones in the case of chlorine- and bromine-bearing complexes, and the reverse was true for the iodine-bearing complexes. Moreover, elevated E int values were recorded for the NH3···â€¢XO3···NH3 trimers over the NH3···â€¢XO3 and •XO3···NH3 dimers, outlining the higher preference of the •XO3 molecules to engage in R• and R•-hole site-based interactions in the trimeric form over the dimeric one. These results might be considered a requisite linchpin for numerous forthcoming supramolecular chemistry and crystal engineering studies.

Heat shock protein (Hsp27)-ceramide synthase (Cers1) protein-protein interactions provide a new avenue for unexplored anti-cancer mechanism and therapy.

Hsp27 is a member of the small heat-shock proteins (sHSPs) - the known cellular line of defence against abnormal protein folding behaviors. Nevertheless, its upregulation is linked to a variety of pathological disorders, including several types of cancers. The ceramide synthases (CerS) mediate the synthesis of ceramide, a critical structural and signaling lipid. Functionally, downstream ceramide metabolites are implicated in the apoptosis process and their abnormal functionality has been linked to anticancer resistance. Studies showed that CerS1 are possibly inhibited by Hsp27 leading to biochemical anticancer effects in vitro. Nevertheless, the nature of such protein-protein interaction (PPI) has not been considerably investigated in molecular terms, hence, we present the first description of the dynamics CerS1-Hsp27 interaction landscapes using molecular dynamics simulations. Time-scale molecular dynamics simulation analysis indicated a system-wide conformational events of decreased stability, increased flexibility, reduced compactness, and decreased folding of CerS1. Analysis of binding energy showed a favorable interaction entailing 56 residues at the interface and a total stabilizing energy of -158 KJ/mol. The CerS1 catalytic domain experienced an opposite trend compared to the protein backbone. Yet, these residues adopted a highly compact conformation as per DCCM and DSSP analysis. Furthermore, conserved residues (SER 212, ASP 213, ALA 240, GLY 243, ASP 319) comprising the substrate shuttling machinery showed notable rigidity implying a restrained ceramide precursor access and assembly; hence, a possible inhibitory mechanism. Findings from this report would streamline a better molecular understanding of CerS1-Hsp27 interactions and decipher its potential avenue toward unexplored anti-cancer mechanisms and therapy.

Immune response, oxidative stress, and histological changes of Wistar rats after being administered with Parascaris equorum antigen.

Worldwide, particularly in developing nations, helminth infections are the leading causes of livestock illness and mortality. Parascaris (P.) equorum, a parasitic worm from the Ascarididae family, significantly impacts the production, health, and working performance of equines. This study aimed to investigate the impact of intraperitoneal sensitization of P. equorum on the immune system, oxidative stress, and histology in Wistar rats. After acclimatization for 7 days, we divided the rats into five groups, each consisting of six rats. Group I, serving as the control, was administered distilled water, followed by groups II (day 7), III (day 14), IV (day 21), and V (day 33). The rats were euthanized every day mentioned (Days 7-33). On day 0, a dosage of 1ml/100 gm rat (containing 500 µg/ml protein content) emulsified crude antigen extract with an incomplete Freund's adjuvant (1:1 volume), followed by a second dose of the same antigen concentration on day 7. To assess the allergenicity of this nematode, we measured a whole blood profile, serum levels of IFN-γ, IL-5, IL-10, IL-13, and IL-33, total immunoglobulins IgE and IgG, and oxidative stress markers. Also, we examined histological changes in the liver, kidney, and spleen. The results showed that values of total leukocyte count, granulocytes, monocytes, and lymphocytes were significantly (P < 0.05) increased on day 14 post-infection relative to other days of investigation. It was found that the levels of total immunoglobulins (IgE and IgG) and cytokines (INF-γ, IL-5, IL-13, and IL-33) on days 14 and 21 were significantly higher than in the control group. At all periods of the experiment, the injected group exhibited significantly higher concentrations of MDA and NO compared to the control group (P < 0.05). Conversely, GSH and CAT levels (P < 0.05) dropped significantly on days 7, 14, and 21. Different rat tissues showed alterations. Ultimately, this study described the detrimental effects of P. equorum crude antigen administration on the immune system, oxidative states, and histological changes of Wistar rats at various intervals.

Thirty-day hospital readmission in females with acute heart failure and breast cancer: A retrospective cohort study from national readmission database.

BACKGROUND: Breast Cancer and cardiovascular diseases are amongst the two leading causes of mortality in the United States, and the two conditions are connected in part because of recognized cardiotoxicity of cancer treatments. The aim of this study is to investigate the predictors risk factors for thirty-day readmission in female breast cancer survivors presenting with acute heart failure. METHODS: This is a retrospective cohort study of acute heart failure (AHF) hospitalization in female patients with breast cancer in 2019 using the National Readmission Database (NRD), which is the largest publicly available all-payer inpatient readmission database in the United States. Our study sample included adult female patients aged 18 years and older. The primary outcome of interest was the rate of 30- day readmission. RESULTS: In 2019, there were 8332 total index admissions for AHF in females with breast cancer and 7776 patients were discharged alive. The mean age was 74.4 years (95% CI: 74, 74.7). The percentage of readmission at 30 days among those discharged alive was 21.8% (n = 1699). Hypertensive heart disease with chronic kidney disease accounted for the majority of readmission in AHF with breast cancer followed by sepsis, acute kidney injury, respiratory failure, pneumonia, and atrial fibrillation. Demographic factors including higher burden of comorbidities predict readmission. The total in-hospital mortality in index admission was 6.67% (n = 556) and for readmitted patients was 8.77% (n = 149). The mean length of stay for index admission was 7.5 days (95% CI: 7.25, 7.75). CONCLUSIONS: Readmission of female breast cancer survivors presenting with AHF is common and largely be attributed to high burden of comorbidities including hypertension, and chronic kidney disease. A focus on close outpatient follow-up will be beneficial in lowering readmissions.

Naturally Occurring Plant-Based Anticancerous Candidates as Potential ERK2 Inhibitors: In-Silico Database Mining and Molecular Dynamics Simulations.

The evolutionarily conserved extracellular signal-regulated kinase 2 (ERK2) is involved in regulating cellular signaling in both normal and pathological conditions. ERK2 expression is critical for human development, while hyperactivation is a major factor in tumor progression. Up to now, there have been no approved inhibitors that target ERK2, and as such, here we report on screening of a naturally occurring plant-based anticancerous compound-activity-target (NPACT) database for prospective ERK2 inhibitors. More than 1,500 phytochemicals were screened using in-silico molecular docking and molecular dynamics (MD) approaches. NPACT compounds with a docking score lower than a co-crystallized LHZ inhibitor (calc.-10.5 kcal/mol) were subjected to MD simulations. Binding energies (ΔGbinding) of inhibitor-ERK2 complexes over the MD course were estimated using an MM-GBSA approach. Based on MM-GBSA//100 ns MD simulations, the steroid zhankuic acid C (NPACT01034) demonstrated greater binding affinity against ERK2 protein than LHZ, with ΔGbinding values of -50.0 and -47.7 kcal/mol, respectively. Structural and energetical analyses throughout the MD course demonstrated stabilization of zhankuic acid C complexed with ERK2 protein. The anticipated ADMET properties of zhankuic acid C indicated minimal toxicity. Moreover, in-silico evaluation of fourteen ERK2 inhibitors in clinical trials demonstrated the higher binding affinity of zhankuic acid C towards ERK2 protein.

Anti-tumor withanolides as signal transducers and activators of transcription 3 (STAT3)-inhibition from Withania obtusifolia.

The Solanaceae family and the Withania genus specifically are rich sources of medicinal plants. Liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS/MS) revealed a predominance of withanolides from an organic extract of Withania obtusifolia. A constructed molecular network uncovered the presence of potentially novel withanolides. A series of withanolides were then isolated and structurally characterized from the extract including two new withanolides (withafolia A and withafolia B) and seven previously reported metabolites. Of the isolated compounds, cytotoxicity of withanolide J, physaperuvin G, and a commercial STAT3 inhibitor (S3I-201) were assessed against a human leukemia HL-60 cell line resulting in IC50 values of 26, 29, and 120 µM, respectively. In silico molecular docking simulations indicate that withanolide J and physaperuvin G can bind as an inhibitor in the active site of STAT3 with docking scores comparable to the selective STAT3 inhibitor, S3I-201.

MiniMed 780G System Use in Type 1 Diabetes During Ramadan Intermittent Fasting: A Systematic Literature Review and Expert Recommendations.

This article offers a systematic literature review (SLR) on the use of the MiniMed 780G automated insulin delivery system (MM780G) in people with type 1 diabetes (PwT1D) during Ramadan intermittent fasting. It also presents consensus recommendations on the use of MM780G during the Ramadan period. The SLR was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. The recommendations resulted from a consensus-forming process involving a panel of experts. The process considered evidence found in the SLR as well as the expert opinions. In total, six studies were included in the SLR. The evidence and expert opinions led to recommendations related to (a) pre-Ramadan counseling of MM780G users who plan to fast; (b) suggested MM780G settings, meal announcement strategy, and safety aspects during Ramadan (including a contingency plan); and (c) post-Ramadan transition into and out of Eid-al-Fitr festivities. The SLR findings showed that the MM780G maintains glycemic control at target in PwT1D during Ramadan (meeting continuous glucose monitoring-based clinical targets proposed by the International Consensus on Time-in-Range) while ensuring low rates of hypoglycemia and diabetic ketoacidosis. Automated insulin delivery also helps PwT1D fast more days of Ramadan compared with users of other less advanced modalities of treatment. Pre-Ramadan guidance on specific aspects of the MM780G along with the International Diabetes Federation and Diabetes and Ramadan International Alliance counseling guidelines is recommended. There is still a challenge with post-Iftar hyperglycemia, which could potentially be mitigated by following the recommendations outlined in this article.

σ-Hole, lone-pair-hole, and π-hole site-based interactions in aerogen-comprising complexes: a comparative study.

Herein, the potential of ZO3 and ZF2 aerogen-comprising molecules (where Z = Ar, Kr, and Xe) to engage in σ-, lp-, and π-hole site-based interactions was comparatively studied using various ab initio computations. For the first time, a premier in-depth elucidation of the external electric field (EEF) influence on the strength of the σ-, lp-, and π-hole site-based interactions within the ZO3/ZF2⋯NH3 and ⋯NCH complexes was addressed using oriented EEF with disparate magnitude. Upon the energetic features, σ-hole site-based interactions were noticed with the most prominent preferability in comparison to lp- and π-hole analogs. This finding was ensured by the negative interaction energy values of -11.65, -3.50, and -2.74 kcal mol-1 in the case of σ-, lp-, and π-hole site-based interactions within the XeO3⋯ and XeF2⋯NH3 complexes, respectively. Detailedly, the strength of the σ- and lp-hole site-based interactions directly correlated with the atomic size of the aerogen atoms and the magnitude of the positively oriented EEF. Unexpectedly, an irregular correlation was noticed for the interaction energies of the π-hole site-based interactions with the size of the π-hole. Interestingly, the π-hole site-based interactions within Kr-comprising complexes exhibited higher negative interaction energies than the Ar- and Xe-comprising counterparts. Notwithstanding, a direct proportion between the interaction energies of the π-hole site-based interactions and π-hole size was obtained by employing EEF along the positive orientation with high strength. The present outcomes would be a fundamental basis for forthcoming progress in studying the σ-, lp-, and π-hole site-based interactions within aerogen-comprising complexes and their pertinent applications in materials science and crystal engineering.

A Comparative DFT Investigation of the Adsorption of Temozolomide Anticancer Drug over Beryllium Oxide and Boron Nitride Nanocarriers.

Herein, attempts were made to explore the adsorption prospective of beryllium oxide (Be12O12) and boron nitride (B12N12) nanocarriers toward the temozolomide (TMZ) anticancer drug. A systematic investigation of the TMZ adsorption over nanocarriers was performed by using quantum chemical density functional theory (DFT). The favorability of Be12O12 and B12N12 nanocarriers toward loading TMZ was investigated through A↔D configurations. Substantial energetic features of the proposed configurations were confirmed by negative adsorption (E ads) energy values of up to -30.47 and -26.94 kcal/mol for TMZ•••Be12O12 and •••B12N12 complexes within configuration A, respectively. As per SAPT results, the dominant contribution beyond the studied adsorptions was found for the electrostatic forces (E elst = -100.21 and -63.60 kcal/mol for TMZ•••B12N12 and •••Be12O12 complexes within configuration A, respectively). As a result of TMZ adsorption, changes in the energy of molecular orbitals followed by alterations in global reactivity descriptors were observed. Various intermolecular interactions within the studied complexes were assessed by QTAIM analysis. Notably, a favorable adsorption process was also observed under the effect of water with adsorption energy ( reaching -28.05 and -22.26 kcal/mol for TMZ•••B12N12 and •••Be12O12 complexes within configuration A, respectively. The drug adsorption efficiency of the studied nanocarriers was further examined by analyzing the IR and Raman spectra. From a sustained drug delivery point of view, the release pattern of TMZ from the nanocarrier surface was investigated by recovery time calculations. Additionally, the significant role of doping by heavy atoms (i.e., MgBe11O12 and AlB11N12) on the favorability of TMZ adsorption was investigated and compared to pure analogs (i.e., Be12O12 and B12N12). The obtained data from thermodynamic calculations highlighted that the adsorption process over pure and doped nanocarriers was spontaneous and exothermic. The emerging findings provide a theoretical base for future works related to nanocarrier applications in the drug delivery process, especially for the TMZ anticancer drug.

Dentifragilones A-B and Other Benzoic Acid Derivatives from the European Basidiomycete Dentipellis fragilis.

A chemical and biological exploration of the European polypore Dentipellis fragilis afforded two previously undescribed natural products (1 and 2), together with three known derivatives (3-5). Chemical structures of the isolated compounds were confirmed through 1D/2D NMR spectroscopic analyses, mass spectrometry, and by comparison with the reported literature. The relative and absolute configurations of 1 were determined according to the ROESY spectrum and time-dependent density functional theory electronic circular dichroism (TDDFT-ECD), respectively. Furthermore, the absolute configuration of dentipellinol (3) was revisited and revealed to be of (R) configuration. All the isolated compounds were assessed for their cytotoxic and antimicrobial activities, with some being revealed to have weak to moderate antimicrobial activity, particularly against Gram-positive bacteria.

Synthesis and Characterization of Naproxen Intercalated Zinc Oxide Stacked Nanosheets for Enhanced Hepatoprotective Potential.

Liver diseases pose a significant global health burden, with limited therapeutic options for chronic cases. Zinc oxide (ZnO) nanomaterials have emerged as promising candidates for hepatoprotection due to their antioxidant, anti-inflammatory, and regenerative properties. However, their potential remains hampered by insufficient drug loading and controlled release. The current study explores the intercalation of Naproxen (Nx), a potent anti-inflammatory and analgesic drug, within ZnO stacked nanosheets (SNSs) to address these limitations. Herein, an easy and solution-based synthesis of novel Nx intercalated ZnO SNSs was established. The obtained Nx intercalated ZnO SNSs were encapsulated with poly(vinyl acetate) (PVA) to make them biocompatible. The synthesized biocomposite was characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR), which confirm the successful synthesis and intercalation of Nx within the ZnO SNSs. The obtained outcomes showed that the configuration of ZnO nanosheets was altered when Nx was introduced, resulting in a more organized stacking pattern. An in vivo investigation of mice liver cells unveiled that the Nx intercalated ZnO SNss had increased hepatoprotective properties. The study's results provide valuable insights into using Nx intercalated ZnO SNss for targeted drug delivery and improved treatment effectiveness, particularly for liver-related illnesses.

Laburnicolamine: A Rare Penillic Acid Congener from the Nematode Cyst-Associated Fungus Laburnicola nematophila.

A chemical investigation of a methanol extract derived from a solid-state rice culture of the nematode-cyst associated fungus Laburnicola nematophila K01 led to the isolation and characterization of a previously undescribed penillic acid analogue named laburnicolamine (1). The chemical structure was elucidated through comprehensive 1D and 2D NMR spectroscopic analyses in methanol-d4 and DMSO-d6, alongside with HR-ESI-MS spectrometry. The absolute configuration of 1 was concluded through the electronic circular dichroism (ECD) and time-dependent density functional theory-ECD (TDDFT-ECD) computations compared to its acquired spectrum. Biological assays revealed that compound 1 exhibited no significant cytotoxic, antimicrobial, or nematicidal activity.

Posterolateral Fusion Versus Posterior Lumbar Interbody Fusion for Adult Low-Grade Isthmic Spondylolisthesis: Analysis of Sagittal Radiographic Parameters - A Randomized Controlled Trial.

STUDY DESIGN: Randomized controlled trial. OBJECTIVES: To compare the effect of posterolateral fusion (PLF) and posterior lumbar interbody fusion (PLIF) on sagittal radiographic parameters in patients with low-grade isthmic spondylolisthesis. Additionally, to explore the correlation between changes in these parameters and clinical outcomes. METHODS: Forty-six consecutive patients with single-level low-grade isthmic spondylolisthesis were initially enrolled. They were randomly assigned to undergo either PLF or PLIF. Patients were followed up for at least 24 months. Radiographic outcomes included pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, sagittal vertical axis, T1 pelvic angle, slip angle, slip degree and disc height. Clinical outcomes were assessed by the Oswestry Disability Index (ODI) and visual analogue scale (VAS). RESULTS: Four participants were lost to follow-up. Of the remaining 42 patients, 29 were female. The mean age was 40.23 ± 10.25 years in the PLF group and 35.81 ± 10.58 years in the PLIF group. There was a statistically significant greater correction of all radiographic parameters in the PLIF group. The ODI and VAS improved significantly in both groups, with no significant differences between the two groups. Changes in the ODI and VAS were significantly correlated with changes in disc height, slip angle and lumbar lordosis. CONCLUSIONS: In patients with low-grade isthmic spondylolisthesis, PLIF demonstrates superior efficacy compared to PLF in correcting sagittal radiographic parameters. Nevertheless, this distinction does not seem to influence short-term clinical results. Restoring disc height, correcting the slip angle, and reestablishing normal lumbar lordosis are crucial steps in the surgical management of isthmic spondylolisthesis.

Recommendations for management of diabetes and its complications during Hajj (Muslim Pilgrimage) - 2024 update.

Hajj is an obligatory duty for all healthy adult Muslims once in the lifetime subjected to the ability. Considering the 10.5 % global prevalence of diabetes coupled with the numbers of Muslims performing the Hajj, ∼ 1.8 million in 2023, it is estimated that Muslims with diabetes performing Hajj may exceed 340,000 this year. During Hajj the pattern and amount of their meal, fluid intake and physical activity are markedly altered. Many people with diabetes insist on doing the Hajj duty, thereby creating a medical challenge for themselves and their health care providers. It is therefore important that medical professionals be aware of the potential risks that may be associated with Hajj. People with diabetes may face many health hazards during Hajj including but not limited to the killer triad which might occur during Hajj: Hypoglycemia, Foot injury and Infections. Many precautions should be taken to prevent and treat these potentially serious complications. Risk stratification, medication adjustments, proper clinical assessment, and education before doing Hajj are crucial.