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•Hesperidin solid lipid nanoparticles (HES-SLNs) were developed by supercritical antisolvent technique.•HES-SLNs improves aqueous solubility and apparent permeability coefficient of ...HES.•HES-SLNs possess improved cardioprotective effects compared to hesperidin.•HES-SLNs effectively attenuates DOX-induced cardiotoxicity via suppression of oxidative stress and apoptosis.
Doxorubicin (DOX) is commonly used for the treatment of many types of cancers but its cardiotoxicity, owing to free radical formation, limits its clinical use. Hesperidin (HES), a flavanone glycoside, has been shown to exert multiple pharmacological actions including cardioprotective effects. Herein, we aim to formulate HES loaded solid lipid nanoparticles (SLNs) using supercritical antisolvent (SAS) technology to improve the oral delivery of HES. Process parameters were optimized to produce small size (175.3 ± 3.6 nm) HES-SLNs with high encapsulation efficiency (87.6 ± 3.8 %). DSC and XRD showed that HES is amorphously dispersed in SLNs. Compared to HES, HES-SLNs resulted in a nearly 20-fold increase in aqueous solubility and a nearly 5-fold increase in apparent permeability. Pharmacokinetics in rats revealed nearly 4.5-fold higher bioavailability of HES from SLN formulation compared to HES suspension. Data showed that HES-SLN significantly attenuated DOX-induced cardiotoxicity through lowering creatine kinase-muscle/brain, cardiac troponin I and improving histopathological scores as compared to the DOX group. HES-SLN also decreased malondialdehyde, increased catalase and superoxide dismutase of rats’ heart to levels relatively comparable to control. Marked reductions in caspase-3 were also observed following HES-SLN treatment. Conclusively, these results describe a cardioprotective effect for HES-SLN against DOX-induced cardiotoxicity likely facilitated via suppression of oxidative stress and apoptosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Protein energy malnutrition (PEM) is a global public health concern, and personalized treatment approaches are crucial for improved outcomes. This study explores the transformative potential of Chat ...GPT, an AI language model, in revolutionizing personalized treatment for PEM. By providing accurate information, personalized dietary recommendations, food choices, psychological counseling of the patient and real-time monitoring and support, Chat GPT can enhance the effectiveness of PEM interventions. Along with the benefits it is also important to acknowledge its potential flaws and limitations. The study emphasizes the importance of collaboration between AI technology and healthcare professionals to leverage Chat GPT's capabilities effectively. By combining human expertise with AI capabilities, personalized PEM treatment can be revolutionized, leading to improved patient outcomes and a comprehensive approach to addressing this global public health concern. The study highlights the significant impact of Chat GPT in providing tailored guidance and continuous support throughout the treatment process, empowering individuals and improving their overall well-being.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This paper examines whether fair value adjustments included in other comprehensive income (OCI) predict future bank performance. It also examines whether the reliability of these estimates affects ...their predictive value. Using a sample of bank holding companies, we find that fair value adjustments included in OCI can predict earnings both 1 and 2 years ahead. However, not all fair value-related unrealized gains and losses included in OCI have similar implications. While net unrealized gains and losses on available-for-sale securities are positively associated with future earnings, net unrealized gains and losses on derivative contracts classified as cash flow hedges are negatively associated with future earnings. We also find that reliable measurement of fair values enhances predictive value. Finally, we show that fair value adjustments recorded in OCI during the 2007–2009 financial crisis predicted future profitability, contradicting criticism that fair value accounting forced banks to record excessive downward adjustments.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In the present study we investigated the protective role of intranasal rosuvastatin liquid crystalline nanoparticles (Ros-LCNPs) against pentylenetetrazole (PTZ) induced seizures, increasing current ...electroshock (ICES) induced seizures, and PTZ-induced status epilepticus. From the dose titration study, it was evident that intranasal rosuvastatin (ROS), at lower dose, was more effective than oral and intraperitoneal ROS. The Ros-LCNPs equivalent to 5 mg/kg ROS were developed by hydrotrope method using glyceryl monooleate (GMO) as lipid phase. The high resolution TEM revealed that the formed Ros-LCNPs were cubic shaped and multivesicular with mean size of 219.15 ± 8.14 nm. The Ros-LCNPs showed entrapment efficiency of 70.30 ± 1.84% and release was found to be biphasic following Korsmeyer–Peppas kinetics. Intranasal Ros-LCNPs (5 mg/kg) showed significant increase in latency to PTZ-induced seizures and ICES seizure threshold compared to control and intranasal ROS solution. Additionally, intranasal Ros-LCNPs provided effective protection against PTZ-induced status epilepticus. No impairment in cognitive functions was observed following intranasal Ros-LCNPs. The results suggested that Ros-LCNPs could be an effective and promising therapeutics for the epilepsy management.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Takotsubo cardiomyopathy (TTC), also known as stress cardiomyopathy or broken heart syndrome, is a condition characterized by transient left ventricular dysfunction resembling myocardial infarction ...but without obstructive coronary artery disease. We present a rare case of a 59-year-old patient with cardiogenic shock (CS) caused by reverse TTC triggered by an undiagnosed right adrenal pheochromocytoma tumor. The patient initially presented with chronic headaches and difficulty breathing, and their condition rapidly deteriorated, necessitating intubation and inotropic support. Diagnostic tests confirmed the diagnosis of reverse TTC, and further investigation revealed an actively growing adrenal mass suggestive of a pheochromocytoma. The patient responded well to treatments, including the use of intra-aortic balloon pump support and subsequent weaning. A right adrenalectomy confirmed the presence of a pheochromocytoma. This case highlights the association between pheochromocytoma and reverse TTC, emphasizing the need to consider this rare etiology in patients presenting with CS. Long-term monitoring is crucial due to the risk of recurrence, even after tumor removal.
A new automated workflow based computationally efficient hydrologic modeling application is developed for soil moisture and runoff simulation. The spatially distributed conceptual framework ...underpinning the Soil Moisture And Runoff simulation Toolkit (SMART) resolves water balance in large upland catchments where topography and land cover are significant drivers of rainfall-runoff transformations. SMART's computational efficiency is achieved by delineation of contiguous and topologically connected hydrologic response units and solving the water balance equation on spatially representative Equivalent Cross-Sections (ECSs). ECSs are formulated by aggregating topographic and physiographic properties of the complete or part of the first order Strahler sub-basins, thereby reducing the number of computational elements. Water balance simulations across the ECSs in two sub-basins illustrated little loss of accuracy compared to the distributed cross section delineations and soil moisture observations. A 2-dimensional Richards' equation based hydrologic model in SMART can be augmented with additional functionalities or replaced with other model structures.
•SMART is a new semi-distributed hydrologic modeling application applied to topologically connected HRUs.•SMART workflow automates sub-basin, HRU and cross section or equivalent cross section delineations of the entire catchment.•SMART reduces computational time of large catchment scale simulations by reducing the number of computational elements.•Temporal dynamics of sub-basin soil moisture are reasonably captured using parameters obtained from soil and land cover data.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Upper gastrointestinal bleeding (UGIB) is a medical emergency with substantial morbidity and mortality worldwide. It is defined as bleeding originating in the gastrointestinal (GI) tract proximal to ...the ligament of Treitz and can be caused by various conditions, including peptic ulcers, gastritis, esophageal varices, Mallory-Weiss tears, and malignancies. Common complications include anemia, hemodynamic instability, perforation, and rebleeding. It is associated with high mortality and a poor prognosis, especially in high-risk populations. Management includes medical treatment, endoscopic intervention, endovascular arterial embolization, and surgery. We present an interesting case of an 87-year-old male with a history of duodenal ulcers who presented with a bleeding duodenal ulcer complicated by recurrent bleeding despite multiple hemostatic endoscopic interventions and arterial embolization. This case highlights the complexities involved in managing recurrent upper GI bleeding and emphasizes the significance of multidisciplinary approaches, timely interventions, and close monitoring.
Ziprasidone (ZP) is a novel atypical antipsychotic agent effective in the treatment of positive and negative symptoms of schizophrenia with low chances for extrapyramidal side effects (EPs) and ...cognitive deficits. ZP possesses poor oral bioavailability (~50%), short biological half-life (~2.5 h) and due to extensive first-pass metabolism, a repeated dose is administered which makes the therapy non-adherent, leading to patient non-compliance. Therefore, this is a first report of developing parenteral ZP loaded sustained release phospholipid based phase-transition system (ZP-LPS).
The ZP-LPS system was formulated by mixing of biocompatible materials including phospholipid E 80, medium chain triglyceride (MCT) and ethanol. Optimization was done by aqueous titration method using pseudo-ternary phase diagram and dynamic rheological measurements. In vivo depot formation was confirmed by gamma scintigraphy after subcutaneous injection. Biodegradation and biocompatibility studies were performed for its safety evaluation. Finally, the efficacy of the formulation was assessed by Morris water maze (MWM) test and dizocilpine (MK-801) was used to induce schizophrenia in Sprague-Dawley rats.
Optimized ZP-LPS showed rapid gelation (2 min), highest change in viscosity (~48000 mPa.s) and sustained release of ZP over a period of 1 month. Gamma scintigraphy depicted that the low-viscosity ZP-LPS system undergo rapid in situ gelation. Biodegradation and biocompatibility studies revealed gradual degradation in size of depot over a period of 28 days without any inflammation at the injection site. In MWM test, escape latency, time spent and total distance in target quadrant were significantly improved (p < 0.001) in the ZP-LPS group in comparison to the MK-801 group when evaluated at day 0, day 7 and day 28. However, significant improvement (p < 0.001) was observed only at day 0 in ZP suspension group.
The overall result indicates that the novel ZP-LPS system is safe, biodegradable, and effective for the management of schizophrenia.
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