METHODS: Paclitaxel (PTX) and tamoxifen (TMX) co-loaded chitosan (CS) nanoparticles (NPs) were prepared using the ionic-gelation method and optimized using the Design Expert® software by controlling different material attributes. For selective targeting through CD44-receptors that are heavily expressed on the BC cells and TAMs, the fabricated NPs (PTX-TMX-CS-NPs) were functionalized with hyaluronic acid (HA) as a targeting ligand.
RESULTS: The optimized HA-PTX-TMX-CS-NPs exhibited desired physicochemical properties (PS ~230 nm, PDI 0.30, zeta potential ~21.5 mV), smooth spherical morphology, high encapsulation efficiency (PTX ~72% and TMX ~97%), good colloidal stability, and biphasic release kinetics. Moreover, the lowest cell viability depicted in MCF-7 (~25%), SK-BR-3 (~20%), and RAW 264.7 cells (~20%), induction of apoptosis, cell cycle arrest, enhanced cell internalization, and alleviation of MCF-7 and SK-BR-3 migration proved the superior anticancer potential of HA-PTX-TMX-CS-NPs compared to unfunctionalized NPs and other control medicines.
CONCLUSION: HA-functionalization of NPs is a promising multiprong strategy for CD44-receptors-mediated targeting of BC cells and TAMs to mitigate the progression, metastasis, and relapse in the BC.
OBJECTIVES: To conduct an extensive literature review and meta-analysis of CBD use for DRE in adult PWE.
DESIGN: Systematic review and meta-analysis.
DATA SOURCES AND METHODS: We conducted a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and two electronic resources; we searched Ovid MEDLINE and Scopus using appropriate keywords until August 2023. Data were presented as standardized mean difference (SMD) and odds ratio with confidence interval (CI) via random effect. We appraised the risk of bias of the included studies using the Joanna Briggs Institute critical appraisal tool while their strength of evidence with the Oxford Centre for Evidence-Based Medicine (OCEBM) and Grading of Recommendations Assessment Development and Education (GRADE) Levels of Evidence.
RESULTS: We identified 16 studies, 3 of which were randomized controlled trials and 3 prospective cohort studies, while the rest were expanded access programs, deriving a total of 668 participants receiving CBD for seizure control. CBD was used concomitantly with antiseizure medications in all studies. There was a statistically significant seizure reduction in the group receiving CBD therapy compared to the placebo group (SMD: -1.50, 95% CI (-3.47, 0.47), p
METHODS: This study aimed to characterize the functional integrity of long white matter tracts in cerebral autosomal-dominant arteriopathy, subcortical infarcts, and leukoencephalopathy transgenic mice expressing R169C mutant Notch3 (Notch3R169C) compared with wild type littermates (Notch3WT), both with and without a superimposed focal white matter lesion in the corpus callosum, utilizing optical resting-state functional connectivity imaging alongside behavioral examinations. In addition, we examined the efficacy of tocotrienol, a neuroprotective derivative of vitamin E derived from palm oil, which has shown promise in preventing white matter disease progression in clinical trials involving patients with small vessel disease.
RESULTS: At baseline, resting-state interhemispheric and intrahemispheric functional connectivity was significantly lower in Notch3R169C than in Notch3WT (P=0.004), and the grid walk test revealed a higher number of foot faults in the Notch3R169C group compared with Notch3WT. Sex did not interact with the genotype on the primary outcomes. Introducing a lesion in the corpus callosum compromised functional connectivity and behavior outcomes in both genotypes to a similar extent; lesion volumes did not differ between the genotypes. Tocotrienol treatment did not show any protective effect on any end point.
CONCLUSIONS: These data show impaired resting-state functional connectivity and increased foot faults in the Notch3R169C mutant model of cerebral autosomal-dominant arteriopathy, subcortical infarcts, and leukoencephalopathy. Future work will aim to test therapeutic or preventive interventions in cerebral autosomal-dominant arteriopathy, subcortical infarcts, and leukoencephalopathy mutants using these measures.
METHODS: Five Schiff base ligands and their complexes were synthesized, characterized, and screened against β-glucuronidase inhibitory activity.
RESULTS: In the series, compounds 3e, 3c, 2b, and 2c ascribed powerful inhibition ranging from (IC50 = 3.0 ± 0.7 µM) to (IC50 = 19.2 ± 0.8 µM). A precise and particular arrangement of atoms is suggested by the triclinic p-1 space group and the existence of a single molecule in an asymmetric unit, which are indispensable for the reactivity as well as the stability of the compounds. The analysis of the Hirshfeld surface provides information about the hydrogen intermolecular and π-π interactions. Based on molecular docking, binding potency increasing by complexation 3a-e compared to ligands 2a-e as well as reference Saccharic acid and uronic isofagomine inhibitor, suggesting that it may be a potent inhibitor of these receptors.
CONCLUSION: The work recognizes latent active compounds for novel β-glucoronidase inhibitors, by further support these may be harnessed for the development of potent drugs.
METHODS: The development of RaHEM followed the ADDIE framework. A comprehensive analysis was conducted through literature reviews, cross-sectional surveys, and stakeholder interviews. The module's content was designed and developed based on the Modified Health Belief Model and Mayer's Cognitive Theory of Multimedia Learning. Validation was performed by a panel of six experts and ten dog owners through content and face validity indices, respectively.
RESULTS: The module was organized into five core topics, each addressing specific aspects of rabies prevention. Content validity indices for all topics exceeded the acceptable threshold of 0.83, with an overall module CVI of 0.91 for relevance and 0.88 for clarity. Face validity indices also surpassed the 0.83 threshold, with overall module FVI scores of 1.00 for understandability and 0.99 for clarity.
CONCLUSION: The RaHEM MOOC was successfully developed and thoroughly validated, ensuring it met its intended objectives and was suitable for the target audience. This educational module offers a promising approach to enhancing rabies prevention through accessible and engaging online education, potentially contributing to reduced rabies transmission and fatalities. Further studies are recommended to evaluate the module's effectiveness in improving rabies knowledge and attitudes.
METHODS: We retrospectively collected and analyzed the clinical data of patients with pathologic diagnosis of PCa from January 1, 2013 to December 31, 2022 in two hospitals in Yangzhou, China. Patients from the Affiliated Hospital of Yangzhou University were divided into a training set and patients from the Affiliated Clinical College of Traditional Chinese Medicine of Yangzhou University were divided into a validation set. Chi-square test, independent sample t-test, and logistic regression were used to screen key risk factors. Receiver operating characteristic (ROC) curves, c-index, calibration curves, and decision curves analysis (DCA) were used for the validation, calibration, clinical benefit assessment, and external validation of nomogram models.
RESULTS: A total of 204 cases were collected from the Affiliated Hospital of Yangzhou University, including 64 cases diagnosed as PCa BM and 50 cases collected from the Affiliated Clinical College of Traditional Chinese Medicine of Yangzhou University, including 12 cases diagnosed as PCa BM. Results showed that history of alcohol consumption, prostate stiffness on Digital rectal examination(DRE), prostate nodules on DRE, FIB, ALP, cTx, and Gleason score were high-risk factors for BM in PCa and nomogram was established. The c-index of the final model was 0.937 (95% CI: 0.899-0.975). And the model was validated by external validation set (c-index: 0.929). The ROC curves and calibration curves showed that the nomogram had good predictive accuracy, and DCA showed that the nomogram had good clinical applicability.
CONCLUSIONS: Our study identified seven high-risk factors for BM in PCa and these factors would provide a theoretical basis for early clinical prevention of PCa BM.
METHOD: Case report and literature review.
RESULT: A 53-year-old gentleman with underlying Stage III B renal cell carcinoma with lung metastasis and gout presented in June 2021 with bilateral red eyes following Coronavirus disease (COVID-19) vaccination. He had undergone a nephrectomy for renal cell carcinoma and was on Pembrolizumab therapy for 5 years. Examination showed right eye injected conjunctiva with diffuse punctate epithelial erosions over the cornea, which was treated with topical steroids. The left eye is suspected to have infective keratitis, which is treated with topical antibiotics and subsequently steroids for the ocular surface inflammation. However, he developed a left eye paracentral sterile corneal melt which rapidly progressed to perforation measuring 1 mm in size. The perforation was temporarily sealed with tissue glue, but he eventually required a full thickness corneal patch graft. Patient has been doing well post-operatively for the last 3 years.
CONCLUSION: The diagnosis and management of irAEs are challenging and necessitate continuously updated diagnostic and monitoring tools. As checkpoint inhibitors become more promising in the management of malignancies, it is crucial for both the oncologist and ophthalmologist to be aware of the potential ocular adverse effects of these drugs.