Perina

DCOIT is an effective antifouling biocide, which presence in the environment and toxicity towards non-target species has been generating great concern. This study evaluated the waterborne toxicity of DCOIT on marine invertebrates (i.e., survival of brine shrimp Artemia sp., larval development of the sea urchin Echinometra lucunter and the mussel Perna perna), as well as DCOIT-spiked-sediment toxicity on the fecundity rate of the copepod Nitrocra sp. And the mortality of the amphipod Tiburonella viscana. The data outcomes were used to calculate environmental hazards and risks, which were compared to their corresponding values obtained from temperate regions...

BACKGROUND: In 2010 the American Heart Association defined the concept of ideal cardiovascular health to renew the focus on primordial prevention for cardiovascular disease. Evidence primarily from high-income countries suggests ideal CVH prevalence is low and decreases with age, with vulnerable populations differentially affected. We aimed to identify and characterize the evidence relevant to CVH metrics in low- and middle-income countries (LMICs). METHODS: We followed the Joanna Briggs Institute guideline for the conduct of this scoping review...

Dysfunction of the androgen receptor (AR) signalling axis plays a pivotal role in the development and progression of prostate cancer (PCa). Steroidal and non-steroidal AR antagonists can significantly improve the survival of PCa patients by blocking the action of the endogenous ligand through binding to the hormone receptor and preventing its activation. Herein, we report two synthetic strategies, each utilizing the advantages of microwave irradiation, to modify the A-ring of natural androgen 5α-dihydrotestosterone (DHT) with pyridine scaffolds...

OBJECTIVE: to verify associations between sociodemographic variables and factors that facilitate and hinder the transition from face-to-face psychological care to remote mode in the first year of the COVID-19 pandemic. METHOD: this is an analytical, quantitative, cross-sectional study. After approval by the Research Ethics Committee, data collection was performed by applying an online form consisting of 55 questions. Data were analyzed using descriptive and inferential statistics techniques...

We analyse two quantum systems with hidden parity-time ([Formula: see text]) symmetry: one is an optical device, whereas another is a superconducting microwave-frequency device. To investigate their symmetry, we introduce a damping frame (DF), in which loss and gain terms for a given Hamiltonian are balanced. We show that the non-Hermitian Hamiltonians of both systems can be tuned to reach an exceptional point (EP), i.e., the point in parameter space at which a transition from broken to unbroken hidden [Formula: see text] symmetry takes place...

The rupture of the Fundão dam, in Brazil, released tons of mining tailings into the Doce River basin (DRB). This investigation aimed to determine the bioaccumulation of metals in soft tissues of the bivalve Corbicula fluminea exposed to sediments collected in the DRB in four periods (just after, 1, 3, and 3.5 years after the dam rupture). In the exposure bioassays, the concentrations of Al, As, Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Zn in sediments and bivalve soft tissues were quantified. The concentration of some elements (As, Cd, Mn, Al) in sediments exceeded the federal limits or regional backgrounds at some sampling sites, but their concentrations tended to decrease along time...

Organotin-based (OTs: TBT and TPT) antifouling paints have been banned worldwide, but recent inputs have been detected in tropical coastal areas. However, there is a lack of studies evaluating the toxicity of both legacy and their substitute antifouling booster biocides (e.g., Irgarol and diuron) on neotropical species. Therefore, the acute toxicity of four antifouling biocides (TBT, TPT, Irgarol, and diuron) was investigated using the marine planktonic organisms Acartia tonsa and Mysidopsis juniae, the estuarine tanaid Monokalliapseudes schubarti (water exposure), and the burrowing amphipod Tiburonella viscana (spiked sediment exposure)...

Targeting cyclin-dependent kinase 7 (CDK7) provides an interesting therapeutic option in cancer therapy because this kinase participates in regulating the cell cycle and transcription. Here, we describe a new trisubstituted pyrazolo[4,3-d]pyrimidine derivative, LGR6768, that inhibits CDK7 in the nanomolar range and displays favourable selectivity across the CDK family. We determined the structure of fully active CDK2/cyclin A2 in complex with LGR6768 at 2.6 Å resolution using X-ray crystallography, revealing conserved interactions within the active site...

Nuclear anxiety, which refers to the fear of nuclear war and its consequences, is expected to increase amid the Russian-Ukrainian War of 2022 (RUW-22). This study aimed to evaluate the prevalence of nuclear anxiety and its associated variables among university students in the Czech Republic during the first weeks of RUW-22. A cross-sectional survey-based study was carried out from March-April 2022, utilizing a digital self-administered questionnaire (SAQ) to collect data from the target population. The SAQ consisted of multiple-choice items inquiring about demographic characteristics; generalized anxiety symptoms using generalized anxiety disorder-7 (GAD-7); depressive symptoms using patient health questionnaire-9 (PHQ-9); and attitudes towards civilian uses of nuclear power, and nuclear war-related anxiety...

Hemophilia A (HA) is one of the most widespread, X-linked, inherited bleeding disorders, which results from defects in the F8 gene. Nowadays, more than 3500 different pathogenic variants leading to HA have been described. Mutation analysis in HA is essential for accurate genetic counseling of patients and their relatives. We analyzed patients from 273 unrelated families with different forms of HA. The analysis consisted of testing for intron inversion (inv22 and inv1), and then sequencing all functionally important F8 gene fragments...

The COVID-19 pandemic has led to a public health crisis, with increases in the number of deaths. As a result, the number of bereaved people has increased significantly. In addition, the measures adopted to control the spread of virus have triggered changes in the subjective and collective bereavement experiences. This systematic literature review aims to summarize and reinterpret the results of qualitative studies on the experience of losing family members during the pandemic by a thematic synthesis. The searches were performed in the Web of Science, Scopus, PubMed/MEDLINE, CINAHL, PsycINFO, and LILACS databases...

Androgen and glucocorticoid receptors have been recently described as key players in processes related to prostate cancer and mainly androgen receptor's inactivation was shown as an effective way for the prostate cancer treatment. Unfortunately, androgen deprivation therapy usually loses its effectivity and the disease frequently progresses into castration-resistant prostate cancer with poor prognosis. The role of the glucocorticoid receptor is associated with the mechanism of resistance; therefore, pharmacological targeting of glucocorticoid receptor in combination with antiandrogen treatment was shown as an alternative approach in the prostate cancer treatment...

Identification, and subsequent quantification of quantum correlations, is critical for understanding, controlling, and engineering quantum devices and processes. We derive and implement a general method to quantify various forms of quantum correlations using solely the experimental intensity moments up to the fourth order. This is possible as these moments allow for an exact determination of the global and marginal impurities of two-beam Gaussian fields. This leads to the determination of steering, tight lower and upper bounds for the negativity, and the Kullback-Leibler divergence used as a quantifier of state nonseparability...

High expression of the androgen receptor (AR) and the disruption of its regulation are strongly responsible for the development of prostate cancer (PCa). Therapeutically relevant non-steroidal or steroidal antiandrogens are able to block the AR effect by eliminating AR-mediated signalling. Herein we report the synthesis of novel steroidal pyrazoles derived from the natural sex hormone 5α-dihydrotestosterone (DHT). 2-Ethylidene or 2-(hetero)arylidene derivatives of DHT obtained by regioselective Claisen-Schmidt condensation with acetaldehyde or (hetero)aromatic aldehydes in alkaline ethanol were reacted with monosubstituted hydrazines to give A-ring-fused 1,5-disubstituted pyrazoles as main or exclusive products, depending on the reaction conditions applied...

Therapy of FLT3-positive acute myeloid leukemia still remains complicated, despite the availability of newly approved kinase inhibitors. Various strategies to avoid the reduced efficacy of therapy have been explored, including the development of dual targeting compounds, which inhibit FLT3 and another kinase necessary for the survival and proliferation of AML cells. We have designed new 2,7,9-trisubstituted 8-oxopurines as FLT3 inhibitors and report here the structure-activity relationship studies. We demonstrated that substituents at positions 7 and 9 modulate activity between CDK4 and FLT3 kinase, and the isopropyl group at position 7 substantially increased the selectivity toward FLT3 kinase, which led to the discovery of compound 15a (9-cyclopentyl-7-isopropyl-2-((4-(piperazin-1-yl)phenyl)amino)-7,9-dihydro-8 H -purin-8-one)...

Mutation of FLT3 protein kinase is often associated with deregulated cell proliferation in acute myeloid leukemia and the inhibition of this kinase is a potential therapeutic strategy. We report a novel series of 3,5,7-trisubstituted pyrazolo[1,5-a]pyrimidines prepared in an effort to study their biological activity particularly toward FLT3-ITD and its downstream regulators as well as toward CDK2 and CDK9. Derivative 10b was capable to strongly inhibit all kinases and its selectivity in FLT3-ITD expressing cell lines MOLM13 and MV4-11 was in line with FLT3-ITD inhibition...

The restrictions on medical students' clinical education during the COVID-19 pandemic has affected their professional readiness and often lengthened their training. These negative impacts are often considered a necessary price as clinical education is hypothesized to be associated with a high risk of pandemic spread. This work assesses this hypothesis based on COVID-19 epidemiological data among Czech dentistry students and their comparison to data of the Czech general population of similar age. We addressed two of the five Czech medical faculties (Charles University, Faculty of Medicine in Hradec Kralove and in Pilsen) providing dentistry study program with a survey...

Steroids with a nitrogen-containing heterocycle in the side chain are known as effective inhibitors of androgen signaling and/or testosterone biosynthesis, thus showing beneficial effects for the treatment of prostate cancer. In this work, a series of 3β-hydroxy-5-ene steroids, containing an isoxazole fragment in their side chain, was synthesized. The key steps included the preparation of Weinreb amide, its conversion to acetylenic ketones, and the 1,2- or 1,4-addition of hydroxylamine, depending on the solvent used...

We describe a novel type of blockade in a hybrid mode generated by linear coupling of photonic and phononic modes. We refer to this effect as hybrid photon-phonon blockade and show how it can be generated and detected in a driven nonlinear optomechanical superconducting system. Thus, we study boson-number correlations in the photon, phonon, and hybrid modes in linearly coupled microwave and mechanical resonators with a superconducting qubit inserted in one of them. We find such system parameters for which we observe eight types of different combinations of either blockade or tunnelling effects (defined via the sub- and super-Poissonian statistics, respectively) for photons, phonons, and hybrid bosons...

Oncogenic mutations in gene encoding FLT3 kinase are often detected in acute myeloid leukaemia (AML) patients, and several potent kinase inhibitors have been developed. However, the FLT3 inhibitor treatment often leads to the resistance development and subsequent relapse. Targeted degradation of oncogenic protein kinases has emerged as a feasible pharmacological strategy, providing more robust effect over traditional competitive inhibitors. Based on previously developed competitive inhibitor of FLT3 and CDK9, we have designed and prepared a novel pomalidomide-based PROTAC...