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.

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.

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 Impact of Sidedness on the Efficacy of Anti-EGFR-Based First-Line Chemotherapy in Advanced Colorectal Cancer Patients in Real-Life Setting-A Nation-Wide Retrospective Analysis (RACER).

Anti-EGFR antibodies combined with chemotherapy doublets are a cornerstone of the upfront treatment of colorectal cancer. RAS and BRAF mutations are established negative predictive factors for such therapy. The primary tumour located in the proximal colon has recently emerged as another negative predictive factor. We have conducted a retrospective multicentre study to collect data on real-world population characteristics, practice patterns, and outcomes in patients with metastatic colorectal cancer treated in a first-line setting with either cetuximab or panitumumab in combination with either FOLFOX or FOLFIRI chemotherapy. The presented analysis focuses on the impact of the primary tumour location. 126 of 842 patients analysed (15.0%) had proximal primary. It was associated with a lower BMI at diagnosis, mucinous histology, and peritoneal metastases. It was also associated with inferior treatment outcomes in terms of response ratio: 59.4% vs. 74.22% (odds ratio [OR] 0.51, 95% CI 0.33-0.78, p = 0.010), and median depth of response: -36.7% vs. -50.0% (p = 0.038). There was only a borderline non-significant trend for inferior PFS in patients with proximal tumours. OS data was incomplete. The presented analysis confirms the negative impact of tumour sidedness on the efficacy of an upfront anti-EGFR-chemotherapy combination and provides valuable data on real-world population characteristics.

Highly Substituted 10-RO-(hetero)acenes-Electric Properties of Vacuum-Deposited Molecular Films.

The functionalization of the aromatic backbone allows the improvement of the electrical properties of acene molecules in the amorphous layered structures of organic thin films. In the present work, we discuss the electric properties of the stable, amorphous, vacuum-deposited films prepared from five highly substituted 10-RO-acenes of various electronic properties, i.e., two extreme electron-donor (1,3-dioxa-cyclopenta[b]) anthracenes with all RO substituents, two anthracene carbaldehydes and one benzo[b]carbazole carbaldehyde possessing both electron-donor and acceptor substituents. The hole mobility data were obtained using subsequent steady state space charge limited currents (SCLC) and Time of Flight (TOF) measurements, performed on the same sample and these were then compared with the results of theoretical hole mobility calculations obtained using the Density Functional Theory (DFT) quantum-chemical calculations using the Marcus-Hush theory. The study shows a good agreement between the theoretical and experimental values which allows for the quick and quantitative estimation of Einstein's mobility values for highly substituted 10-RO anthracene and benzo[b]carbazole based on chemical calculations. This agreement also proves that the transport of holes follows the hopping mechanism. The theoretical calculations indicate that the reorganization energy plays a decisive role in the transport of holes in the amorphous layers of highly substituted hetero(acenes).

Can Pharmaceutical Excipients Threaten the Aquatic Environment? A Risk Assessment Based on the Microtox® Biotest.

The ecotoxicological impact of pharmaceuticals has received considerable attention, primarily focusing on active pharmaceutical ingredients (APIs) while largely neglecting the potential hazards posed by pharmaceutical excipients. Therefore, we analyzed the ecotoxicity of 16 commonly used pharmaceutical excipients, as well as 26 API-excipient and excipient-excipient mixtures utilizing the Microtox® test. In this way, we assessed the potential risks that pharmaceutical excipients, generally considered safe, might pose to the aquatic environment. We investigated both their individual ecotoxicity and their interactions with tablet ingredients using concentration addition (CA) and independent action (IA) models to shed light on the often-overlooked ecotoxicological consequences of these substances. The CA model gave a more accurate prediction of toxicity and should be recommended for modeling the toxicity of combinations of drugs with different effects. A challenge when studying the ecotoxicological impact of some pharmaceutical excipients is their poor water solubility, which hinders the use of standard aquatic ecotoxicity testing techniques. Therefore, we used a modification of the Microtox® Basic Solid Phase protocol developed for poorly soluble substances. The results obtained suggest the high toxicity of some excipients, i.e., SLS and meglumine, and confirm the occurrence of interactions between APIs and excipients. Through this research, we hope to foster a better understanding of the ecological impact of pharmaceutical excipients, prompting the development of risk assessment strategies within the pharmaceutical industry.

The cutaneous stress response system in three-spined stickleback and European flounder exposed to oxidative stress: Different mode of action.

In fish, the skin is directly exposed to multiple environmental stressors and provides the first line of defense against harmful external factors. It turned out that cortisol and melatonin (Mel) are involved in fish cutaneous stress response system (CSRS) similar to mammalian. This study investigates the mode of action of CSRS in two teleost species of different biology and skin characteristics, the three-spined stickleback and the European flounder, after exposure to oxidative stress induced by a potassium dichromate solution. The cutaneous stress response system presents different ways of action in two studied species: Mel concentration increases in the skin of both species, but cortisol concentration increases in the skin only in sticklebacks. Data suggest that stickleback skin cells can produce cortisol. However, cortisol is not involved in the response to oxidative stress in flounders. In stickleback skin, two genes encoding AANAT and ASMT/HIOMT (enzymes involved in Mel synthesis), aanat1a and asmt2, are expressed, but in flounder skin, only one, asmtl. Because gene expression does not change in stickleback skin after exposure to stress, the source of increased Mel is probably outside the skin. A lack of expression of the gene encoding AANAT in flounder skin strongly suggests that Mel is transported to the skin by the bloodstream from other sites of synthesis. Pigment dispersion in the skin after exposure to oxidative stress is found only in sticklebacks.

Gestational Hypertension and Human Breast Milk Composition in Correlation with the Assessment of Fetal Growth-A Pilot Study.

BACKGROUND AND AIMS: 1 in 10 pregnant women is diagnosed with gestational hypertension. Increasing evidence suggests that preeclampsia, gestational diabetes and gestational hypertension may affect human breast milk's lactogenesis and percentage composition. We aimed to examine whether there is any significant influence of gestational hypertension on the composition of macronutrients in human breast milk and to assess its correlation with fetal growth. METHODS: A total of 72 breastfeeding women (34 diagnosed with gestational hypertension and 38 normotensive women during pregnancy) were recruited to the study at the Division of Neonatology, Medical University of Gdansk, between June and December 2022. Milk samples were collected between the 3rd and 6th day of lactogenesis. Samples were analyzed using the Miris HMA™ Human Milk Analyzer (Upsala, Sweden), which evaluates the milk composition's energy, fat, carbohydrate and protein quantity. In addition, we assessed the children's anthropometric measurements (birth weight, body length and head circumference at birth). We used logistic regression to estimate the adjusted odds ratio and 95% confidence interval. RESULTS: The mean (±standard deviation) macronutrient composition per 10 mL of milk in the GH group was 2.5 g (±0.9) of fat, 1.7 g (±0.3) of true protein, 7.7 g (±0.3) of carbohydrates and 63.2 g (±8.1) of energy, in the normotensive women group 1.0 g (±0.9) of fat, 1.7 g (±0.3) of true protein, 7.3 g (±0.4) of carbohydrates and 57.9 g (±8.6) of energy content, respectively. The fat composition was higher in the PIH group by a mean of 0.6 g (p < 0.005). Gestational hypertension had a positive, significant correlation with birth weight (p < 0.013) and the mother's pre-pregnancy weight (p < 0.005). CONCLUSIONS: In conclusion, we found significant differences between milk composition in postpartum women with gestational hypertension compared to healthy, normotensive women. Human milk from women with gestational hypertension was found to contain a higher composition of fat, carbohydrates and energy in comparison to healthy women. Our aim is to further evaluate this correlation, as well as to assess the growth rate of newborns in order to determine the need for individualized formulas for women with pregnancy-induced hypertension, those with poor lactogenesis and those who cannot or choose not to breastfeed.

O,S-Acetals in a New Modification of oxo-Friedel-Crafts-Bradsher Cyclization-Synthesis of Fluorescent (Hetero)acenes and Mechanistic Considerations.

This paper presents the use of O,S-acetals in a new modification of the oxo-Friedel-Crafts-Bradsher cyclization. In this reaction, under mild reaction conditions (25 °C), three- and four-ring fused RO-acenes (major) and/or HO(CH2)2S-acenes (minor) are formed, the latter products having never been observed before in this type of cyclization. In this way, two electronically different fluorophores could be obtained in a single cyclization reaction, one of them having strong electron donor properties (+M effect of alkoxy groups) and the other having donor-acceptor properties (+M and -I effects of the HO(CH2)2S-group, Hammett's constants). Further increasing the reaction temperature, HCl concentration or prolonging reaction time, surprisingly, yielded a 2:1 mixture of cis and trans dimeric isomers, as the only products of this cyclization. The DFT calculations confirmed a greater stability of the cis isomer compared to the trans isomer. The formation of unexpected dimeric products and HO(CH2)2S-acenes sheds light on the mechanism of oxo-Friedel-Crafts-Bradsher cyclization, involving competitive O/S atom protonation in strained O,S-acetals and in strain-free side groups of intermediate species.

Comprehensive Review on Synthesis, Properties, and Applications of Phosphorus (PIII, PIV, PV) Substituted Acenes with More Than Two Fused Benzene Rings.

This comprehensive review, covering the years 1968-2022, is not only a retrospective investigation of a certain group of linearly fused aromatics, called acenes, but also a presentation of the current state of the knowledge on the synthesis, reactions, and applications of these compounds. Their characteristic feature is substitution of the aromatic system by one, two, or three organophosphorus groups, which determine their properties and applications. The (PIII, PIV, PV) phosphorus atom in organophosphorus groups is linked to the acene directly by a P-Csp2 bond or indirectly through an oxygen atom by a P-O-Csp2 bond.

From the Difficult Airway Management to Diagnosis of Retropharyngeal Synovial Cell Carcinoma.

Respiratory complications are among the most common problems addressed in neonatology in the first hours after birth, whereas the risk of any cancer in the neonatal period is 28 per million. Sarcomas, malignant mesenchymal neoplasms, account for about 8% of all neoplasms in the neonatal period. We report on a male neonate born at 36 + 4/7 weeks of gestation, diagnosed with retropharyngeal synovial carcinoma. Ineffective respiratory movements and generalized cyanosis were the first symptoms to be noted. On the ultrasound examination of the neck, a tumor of the retropharyngeal space was exposed, then visualized by an MRI of the head and neck. The biopsy analysis revealed the diagnosis of an extremely rare tumor in a neonate. The location of its growth was atypical, contributing to a diagnostic challenge. The neoplasm was treated solely with chemotherapy concordantly with the CWS protocol, individually customized for our patient. Preterm birth, as in our case, 36 + 4/7 weeks of gestation, may imply a possible need for resuscitation or support in the transition period. Aggressive high-grade tumors of the head and neck region are locally invasive and prone to metastasize. However, prognosis in infants is hard to estimate, therefore both individualized treatment and multidisciplinary care should be tailored to the needs of the patient.

"Motivations, demography, and clinical features of body dysmorphic disorder among people seeking cosmetic treatments: A study of 199 patients".

BACKGROUND: Motivations for getting aesthetic medicine treatments concern not only the improvement of the physical appearance but also internal aspects such as feeling more confident or happier. Body dysmorphic disorder (BDD) is a disorder that affects from 5 to 15% of aesthetic medicine clients and characterizes by an obsessive preoccupation with a non-visible or minimal defect in appearance. AIMS: The aim of the study was to assess the main motivations, demography, and clinical features of body dysmorphic disorder among people seeking cosmetic treatments. METHODS: A single-center study was performed using an anonymous questionnaire on 199 patients of the private aesthetic medicine clinic in Gdansk, Poland. RESULTS: A typical client of an aesthetic clinic is a woman aged 40 to 50, with higher education, who undergoes aesthetic treatments more than twice a year, mainly with botulinum toxin injections. The most common motivations are the desire to achieve a fresh look, the will to reduce the signs of aging, and to invest in oneself. Furthermore, over 38% of patients stated that they were having critical and recurring thoughts about their appearance, which affected their daily functioning and caused a decrease in their well-being. Almost 20% of them performed repetitive activities, such as frequently looking in the mirror or asking others for opinions about their appearance. 15.6% of patients presented at least two characteristic features of BDD. CONCLUSIONS: Patients seeking cosmetic treatments may suffer from body dysmorphic disorder, thus the need for aesthetic medicine practitioners to be aware of this disease.

Melatonin and cortisol as components of the cutaneous stress response system in fish: Response to oxidative stress.

The skin being a passive biological barrier that defends the organism against harmful external factors is also a site of action of the system responding to stress. It appears that melatonin (Mel) and its biologically active metabolite AFMK (N1-acetyl-N2-formyl-5-methoxykynuramine), both known as effective antioxidants, together with cortisol, set up a local (cutaneous) stress response system (CSRS) of fish, similar to that of mammals. Herein we comment on recent studies on CSRS in fish and show the response of three-spined stickleback skin to oxidative stress induced by potassium dichromate. Our study indicates that exposure of the three-spined stickleback to K2Cr2O7 affects Mel and cortisol levels and pigment dispersion in melanophores in the skin. In our opinion, an increased concentration of Mel and cortisol in the skin may be the strategy to cope with oxidative stress, where both components act locally to prevent damage caused by active oxygen molecules. Furthermore, the pigment dispersion may be a valuable, easy-to-observe mark of oxidative stress, useful in the evaluation of fish welfare.

Organosulfur Materials with High Photo- and Photo-Oxidation Stability: 10-Anthryl Sulfoxides and Sulfones and Their Photophysical Properties Dependent on the Sulfur Oxidation State.

While few studies show only symmetrical and poorly mono-SOn (n = 0-2) substituted acenes, in this study, we present a synthesis of a new group of unsymmetrical, significantly substituted derivatives, which revealed unique photophysical properties. Both sulfides (S), sulfoxides (SO) and sulfones (SO2) showed very high photochemical stabilities, unusual for these groups, during UV-irradiation at 254/365 nm (air O2 and Ar), which was higher than any found in the literature. For the (S)/(SO) series (254 nm), the stabilities of 80-519 min. (air O2 and Ar) were found. At 365 nm, stabilities of 124-812 min./(air O2) for (S)/(SO) and higher for (SO2) were observed. Photoluminescence lifetimes of (SOn) of the lower anthryl symmetry remained in the following order: (SO2) < (S) < (SO); those with full symmetry were in the following order: (S) < (SO) < (SO2). The enhanced photostability was explained with DFT/MS/Hammett's constants, which showed the leading role of the SOn groups in stabilization of HOMO/LUMO frontier orbitals. The SOn (n = 0-2) substituted acenes turned out to be tunable violet/blue/green emitters by oxidation of S atoms and the introduction of rich substitution.

Role of Hydrogen Bonds in Formation of Co-amorphous Valsartan/Nicotinamide Compositions of High Solubility and Durability with Anti-hypertension and Anti-COVID-19 Potential.

Physicochemical properties, in particular solubility and the associated bioavailability, are key factors in determining efficacy of poorly water-soluble drugs, which constitute 40% of new drugs in the market, and improving them is an important challenge for modern pharmacy. A recent strategy to achieve this goal is formation of stable co-amorphous solid dispersions with co-formers of low molecular weight. Here, the amorphization strategy was applied for low-soluble anti-hypertensive valsartan (VAL), an angiotensin II receptor blocker, and nicotinamide, which exhibits lung- and cardio-protective effects. Through interactions with the renin-angiotensin-aldosteron system, VAL may be used to treat both hypertension and the current pandemic coronavirus SARS-CoV-2 infection. Using mechanochemical and liquid- and solid-state approaches, solvated co-amorphous solid dispersions of VAL with nicotinamide were obtained. They were characterized by spectroscopic, thermal, and X-ray analyses. The density functional theory, quantum theory of atoms in molecules, and non-covalent interaction index calculations revealed the presence of two types of hydrogen bonds between VAL and NIC (i.e., N-H···O and O-H···O). One of them had a partially covalent character, which caused conformational changes in the flexible VAL molecule, restricting contribution of the tetrazolyl N-H donor and thus limiting the possibility of co-crystal formation. The recognized VAL/NIC1- and VAL/NIC2-type heterodimeric interactions were responsible for the excellent durability of the solid compositions and up to 24-fold better solubility than VAL alone. The synthesized dispersions constitute a new class of dually acting drugs, containing an active pharmaceutical ingredient (VAL) and supporting nutraceutical (nicotinamide).

The circadian gene Cryptochrome 2 influences stress-induced brain activity and depressive-like behavior in mice.

Cryptochrome 2 (Cry2) is a core clock gene important for circadian regulation. It has also been associated with anxiety and depressive-like behaviors in mice, but the previous findings have been conflicting in terms of the direction of the effect. To begin to elucidate the molecular mechanisms of this association, we carried out behavioral testing, PET imaging, and gene expression analysis of Cry2-/- and Cry2+/+ mice. Compared to Cry2+/+ mice, we found that Cry2-/- mice spent less time immobile in the forced swim test, suggesting reduced despair-like behavior. Moreover, Cry2-/- mice had lower saccharin preference, indicative of increased anhedonia. In contrast, we observed no group differences in anxiety-like behavior. The behavioral changes were accompanied by lower metabolic activity of the ventro-medial hypothalamus, suprachiasmatic nuclei, ventral tegmental area, anterior and medial striatum, substantia nigra, and habenula after cold stress as measured by PET imaging with a glucose analog. Although the expression of many depression-associated and metabolic genes was upregulated or downregulated by cold stress, we observed no differences between Cry2-/- and Cry2+/+ mice. These findings are consistent with other studies showing that Cry2 is required for normal emotional behavior. Our findings confirm previous roles of Cry2 in behavior and extend them by showing that the effects on behavior may be mediated by changes in brain metabolism.

The hetero-Friedel-Crafts-Bradsher Cyclizations with Formation of Ring Carbon-Heteroatom (P, S) Bonds, Leading to Organic Functional Materials.

The interest in functional materials possessing improved properties led to development of new methods of their synthesis, which allowed to obtain new molecular arrangements with carbon and heteroatom motifs. Two of the classical reactions of versatile use are the Friedel-Crafts and the Bradsher reactions, which in the new heteroatomic versions allow to replace ring carbon atoms by heteroatoms. In the present work, we review methods of synthesis of C-S and C-P bonds utilizing thia- and phospha-Friedel-Crafts-Bradsher cyclizations. Single examples of C-As and lack of C-Se bond formation, involving two of the closest neighbors of P and S in the periodic table, have also been noted. Applications of the obtained π-conjugated molecules, mainly as semiconducting materials, flame retardants, and resins hardeners, designed on the basis of five- and six-membered cyclic molecules containing ring phosphorus and sulfur atoms, are also included. This comprehensive review covers literature up to August 2020.

Modification of the Microtox® Basic Solid Phase Test: A new application for the ecotoxicological studies on poorly soluble antihypertensive drugs.

Increasing consumption of angiotensin II receptor blockers (ARBs: valsartan, losartan potassium, telmisartan) is inevitably associated with their appearance in the environment and impact on aquatic and terrestrial organisms. Since the pharmaceuticals do not occur as pure substances in the environment, but as complex mixtures with other active pharmaceutical ingredients (APIs) and excipients used in pharmaceutical formulations, we compared the ecotoxicity of ARBs in various forms: as pure APIs, in pharmaceutical formulations and in mixtures with hydrochlorothiazide (HCT). Because the studied APIs are poorly water-soluble, the Microtox® Basic Solid Phase Test, utilizing bacteria Aliivibrio fischeri, has been modified by using a neutral matrix. Thus, this test, which is correlated with other tests for higher aquatic organisms, may be applied for the ecotoxicological evaluation of poorly soluble APIs. This is the first study reflecting the real situation in the environment, where non-target species are exposed to the pharmaceuticals, which can be dissolved/suspended in the liquid medium or adsorbed on the solid matrix. The results obtained indicate that the excipients are not inert substances and their presence in the environment may cause an increased risk to non-target organisms. Moreover, antagonistic effects were observed for two-component drug-drug (ARBs-HCT) mixtures.