New Perspectives for Antihypertensive Sartans as Components of Co-crystals and Co-amorphous Solids with Improved Properties and Multipurpose Activity.

Sartans (angiotensin II receptor blockers, ARBs), drugs used in the treatment of hypertension, play a principal role in addressing the global health challenge of hypertension. In the past three years, their potential use has expanded to include the possibility of their application in the treatment of COVID-19 and neurodegenerative diseases (80 clinical studies worldwide). However, their therapeutic efficacy is limited by their poor solubility and bioavailability, prompting the need for innovative approaches to improve their pharmaceutical properties. This review discusses methods of co-crystallization and co-amorphization of sartans with nonpolymeric, low molecular, and stabilizing co-formers, as a promising strategy to synthesize new multipurpose drugs with enhanced pharmaceutical properties. The solid-state forms have demonstrated the potential to address the poor solubility limitations of conventional sartan formulations and offer new opportunities to develop dual-active drugs with broader therapeutic applications. The review includes an in-depth analysis of the co-crystal and co-amorphous forms of sartans, including their properties, possible applications, and the impact of synthetic methods on their pharmacokinetic properties. By shedding light on the solid forms of sartans, this article provides valuable insights into their potential as improved drug formulations. Moreover, this review may serve as a valuable resource for designing similar solid forms of sartans and other drugs, fostering further advances in pharmaceutical research and drug development.

The First Example of the Friedel-Crafts Cyclization Leading to (10-Hydroxy-9,10-dihydroanthr-9-yl)phosphonium Salts without the Expected Bradsher Dehydration.

The reaction of (ortho-acetalaryl)arylmethanols with various phosphines PR1R2R3 (R1 = R2 = R3 = Ph; R1 = R2 = Ph, R3 = Me and R1 = R2 = Me, R3 = Ph) under acidic conditions (e.g., HCl, HBF4, TsOH) unexpectedly led to the formation of (10-hydroxy-9,10-dihydroanthr-9-yl)phosphonium salts instead of the corresponding anthryl phosphonium salts. The cyclization occurred according to the Friedel-Crafts mechanism but without the usually observed Bradsher dehydration, giving cyclic products in the form of cis/trans isomers and their conformers. In case of electron-rich and less-hindered dimethylphenylphosphine, all four stereoisomers were recorded in 31P{1H} NMR spectra, while for the other phosphines, only the two most stable cis/trans stereoisomers were detected. This study was supported by DFT and NCI calculations in combination with FT-IR analysis.

Diagnostic Utility of Selected Matrix Metalloproteinases (MMP-2, MMP-3, MMP-11, MMP-26), HE4, CA125 and ROMA Algorithm in Diagnosis of Ovarian Cancer.

Ovarian cancer (OC) has an unfavorable prognosis. Due to the lack of effective screening tests, new diagnostic methods are being sought to detect OC earlier. The aim of this study was to evaluate the concentration and diagnostic utility of selected matrix metalloproteinases (MMPs) as OC markers in comparison with HE4, CA125 and the ROMA algorithm. The study group consisted of 120 patients with OC; the comparison group consisted of 70 patients with benign lesions and 50 healthy women. MMPs were determined via the ELISA method, HE4 and CA125 by CMIA. Patients with OC had elevated levels of MMP-3 and MMP-11, similar to HE4, CA125 and ROMA values. The highest SE, SP, NPV and PPV values were found for MMP-26, CA125 and ROMA in OC patients. Performing combined analyses of ROMA with selected MMPs increased the values of diagnostic parameters. The topmost diagnostic power of the test was obtained for MMP-26, CA125, HE4 and ROMA and performing combined analyses of MMPs and ROMA enhanced the diagnostic power of the test. The obtained results indicate that the tested MMPs do not show potential as stand-alone OC biomarkers, but can be considered as additional tests to raise the diagnostic utility of the ROMA algorithm.

A machine learning approach to evaluate the impact of virtual balance/cognitive training on fall risk in older women.

Introduction: Novel technologies based on virtual reality (VR) are creating attractive virtual environments with high ecological value, used both in basic/clinical neuroscience and modern medical practice. The study aimed to evaluate the effects of VR-based training in an elderly population. Materials and methods: The study included 36 women over the age of 60, who were randomly divided into two groups subjected to balance-strength and balance-cognitive training. The research applied both conventional clinical tests, such as (a) the Timed Up and Go test, (b) the five-times sit-to-stand test, and (c) the posturographic exam with the Romberg test with eyes open and closed. Training in both groups was conducted for 10 sessions and embraced exercises on a bicycle ergometer and exercises using non-immersive VR created by the ActivLife platform. Machine learning methods with a k-nearest neighbors classifier, which are very effective and popular, were proposed to statistically evaluate the differences in training effects in the two groups. Results and conclusion: The study showed that training using VR brought beneficial improvement in clinical tests and changes in the pattern of posturographic trajectories were observed. An important finding of the research was a statistically significant reduction in the risk of falls in the study population. The use of virtual environments in exercise/training has great potential in promoting healthy aging and preventing balance loss and falls among seniors.

Clinical image of sepsis-associated encephalopathy midst E. coli urosepsis: Emergency department database study.

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, which, if untreated, leads to multi-organ failure. One of the severe possible complications is sepsis associated encephalopathy (SAE), a neurological dysfunction occurring secondary to a severe inflammatory response. It manifests as acute cognitive dysfunction and sudden-onset dysfunctions in mental state. Uropathogenic Escherichia coli is the most common pathogen causing bacteremia, responsible for 80% of uncomplicated outpatient urinary tract infections and 40% of nosocomial infections. The study aimed to assess the difference in the severity and the course of urosepsis caused by E. coli in patients with and without septic encephalopathy. Materials and methods: This study presents a retrospective analysis of the population of urosepsis patients admitted to the Emergency Department between September 2019 and June 2022. Inflammatory parameters, urinalysis and blood cultures were performed, along with a clinical evaluation of sepsis severity and encephalopathy. The patients were then stratified into SAE and non-SAE groups based on neurological manifestations and compared according to the collected data. Results: A total of 199 septic patients were included in the study. E. coli-induced urosepsis was diagnosed in 84 patients. In this group, SAE was diagnosed in 31 (36.9%) patients (33.3% in males, 40.5% females). Patients with SAE were found to be hypotensive (p < 0,005), with a higher respiratory rate (p < 0,017) resulting in a higher mortality rate (p = 0.002) compared to non-SAE septic patients. The APACHE II score was an independent risk factor associated with a higher mortality rate. Biochemical parameters between the groups did not show any statistical importance related to the severity of urosepsis. Conclusions: The severity of urosepsis and risk of SAE development increase according to the clinical condition and underlying comorbidities. Urosepsis patients with SAE are at a higher risk of death. Patients should undergo more careful screening for the presence of SAE on admission, and more intense monitoring and treatment should be provided for patients with SAE. This study indicates the need to develop projects aiming to further investigate neuroprotective interventions in sepsis.