Automated volumetric evaluation of intracranial compartments and cerebrospinal fluid distribution on emergency trauma head CT scans to quantify mass effect

BackgroundIntracranial space is divided into three compartments by the falx cerebri and tentorium cerebelli. We assessed whether cerebrospinal fluid (CSF) distribution evaluated by a specifically developed deep-learning neural network (DLNN) could assist in quantifying mass effect.MethodsHead trauma CT scans from a high-volume emergency department between 2018 and 2020 were retrospectively analyzed. Manual segmentations of intracranial compartments and CSF served as the ground truth to develop a DLNN model to automate the segmentation process. Dice Similarity Coefficient (DSC) was used to evaluate the segmentation performance. Supratentorial CSF Ratio was calculated by dividing the volume of CSF on the side with reduced CSF reserve by the volume of CSF on the opposite side.ResultsTwo hundred and seventy-four patients (mean age, 61 years ± 18.6) after traumatic brain injury (TBI) who had an emergency head CT scan were included. The average DSC for training and validation datasets were respectively: 0.782 and 0.765. Lower DSC were observed in the segmentation of CSF, respectively 0.589, 0.615, and 0.572 for the right supratentorial, left supratentorial, and infratentorial CSF regions in the training dataset, and slightly lower values in the validation dataset, respectively 0.567, 0.574, and 0.556. Twenty-two patients (8%) had midline shift exceeding 5 mm, and 24 (8.8%) presented with high/mixed density lesion exceeding >25 ml. Fifty-five patients (20.1%) exhibited mass effect requiring neurosurgical treatment. They had lower supratentorial CSF volume and lower Supratentorial CSF Ratio (both p < 0.001). A Supratentorial CSF Ratio below 60% had a sensitivity of 74.5% and specificity of 87.7% (AUC 0.88, 95%CI 0.82–0.94) in identifying patients that require neurosurgical treatment for mass effect. On the other hand, patients with CSF constituting 10–20% of the intracranial space, with 80–90% of CSF specifically in the supratentorial compartment, and whose Supratentorial CSF Ratio exceeded 80% had minimal risk.ConclusionCSF distribution may be presented as quantifiable ratios that help to predict surgery in patients after TBI. Automated segmentation of intracranial compartments using the DLNN model demonstrates a potential of artificial intelligence in quantifying mass effect. Further validation of the described method is necessary to confirm its efficacy in triaging patients and identifying those who require neurosurgical treatment

Pluronic® F-127 enhances antifungal activity of fluconazole against resistant Candida strains

Candida strains as the most frequent causes of infections, along with their increased drug resistance, pose significant clinical and financial challenges to the healthcare system. Some polymeric excipients were reported to interfere with the multidrug resistance mechanism. Bearing in mind that there are a limited number of marketed products with fluconazole (FLU) for the topical route of administration, Pluronic F-127 (PLX)/FLU formulations were investigated in this work. The aims of this study were to investigate (i) whether PLX-based formulations can increase the susceptibility of resistant Candida strains to FLU, (ii) whether there is a correlation between block polymer concentration and the antifungal efficacy of the FLU-loaded PLX formulations, and (iii) what the potential mode of action of PLX assisting FLU is. The yeast growth inhibition upon incubation with PLX formulations loaded with FLU was statistically significant. The highest efficacy of the azole agent was observed in the presence of 5.0 and 10.0% w/v of PLX. The upregulation of the CDR1/CDR2 genes was detected in the investigated Candida strains, indicating that the efflux of the drug from the fungal cell was the main mechanism of the resistance

Ribosomal RNA of Hyacinthus orientalis L. female gametophyte cells before and after fertilization

The nucleolar activity of Hyacinthus orientalis L. embryo sac cells was investigated. The distributions of nascent pre-rRNA (ITS1), 26S rRNA and of the 5S rRNA and U3 snoRNA were determined using fluorescence in situ hybridization (FISH). Our results indicated the different rRNA metabolism of the H. orientalis female gametophyte cells before and after fertilization. In the target cells for the male gamete, i.e., the egg cell and the central cell whose activity is silenced in the mature embryo sac (Pięciński et al. in Sex Plant Reprod 21:247–257, 2008; Niedojadło et al. in Planta doi:10.1007/s00425-012-1599-9, 2011), rRNA metabolism is directed at the accumulation of rRNPs in the cytoplasm and immature transcripts in the nucleolus. In both cells, fertilization initiates the maturation of the maternal pre-rRNA and the expression of zygotic rDNA. The resumption of rRNA transcription observed in the hyacinth zygote indicates that in plants, there is a different mechanism for the regulation of RNA Pol I activity than in animals. In synergids and antipodal cells, which have somatic functions, the nucleolar activity is correlated with the metabolic activity of these cells and changes in successive stages of embryo sac development

Earth's field NMR imaging with use of spin and gradient echo

Przedmiotem pracy było przeprowadzenie pomiarów opartych na obrazowaniu NMR w ziemskim polu magnetycznym z użyciem metod echa spinowego i echa gradientowego. Dodatkowo wykonano pomiary czasów relaksacji badanych substancji. Prezentowane wyniki zawierają obrazy następujących próbek: wody destylowanej, wody wodociągowej, wody spożywczej „Kropla Beskidu”, roztworu siarczanu(VI) miedzi(II) o stężeniach 0,01% oraz 0,02%, etanolu o stężeniu 99,8%, (2,2,2)- trifluoroetanolu oraz żelatyny spożywczej. Każda z wymienionych substancji prezentowała rozkład gęstości protonowej związany z jej budową chemiczną. W swojej pracy skoncentrowałam się na obrazowaniu metodą echa spinowego. Wykazano, że za pomocą obrazowania metodą echa spinowego zyskuje się lepszy odczyt rozkładu gęstości protonowej. Przedmiotem obserwacji był głównie rozkład gęstości jąder wodoru. Najsilniejsze sygnały obserwowano dla wody destylowanej oraz wodociągowej. Ciekawy rozkład gęstości protonowej zaobserwowano w przypaku (2,2,2)- trifluoroetanolu. Dla wymienionych substancji wykonano pomiary czasu relaksacji podłużnej, metodą T1Be oraz czasu relaksacji poprzecznej. Najdłuższe czasy relaksacji dotyczą wody destylowanej oraz spożywczej. Wybór metody pomiaru czasu relaksacji podłużnej uzasadniono lepszym rozkładem uzyskiwanych danych. Z wykorzystaniem podanych odczynników sporządzono również fantomy o złożonej strukturze. Fantomy te to: układ dwóch probówek wypełnionych roztworami CuSO4 oraz układ mikrorurek umieszczonych w pojemniku o niewielkiej średnicy. Złożenie fantomów służyło odczytaniu kontrastu pomiędzy rozkładem gęstości protonowej pomiędzy substancjami, które różniły się stężeniami procentowymi. Dzięki złożonej strukturze fantomów zaobserwowano również, że pomiar w ziemskim polu magnetycznym nie jest odpowiedni dla obiektów, które mają zbyt małe rozmiary. Obrazowane mikrorurki nie pokazują takiego wymiaru gęstości na podstawie, którego można wnioskować o różnicach między obserwowanym sygnałem a obszarem otaczającym próbkę. Wyniki pracy pokazują, że pomiar zjawiska NMR jest możliwy w zewnętrznym, słabym polu magnetycznym jakim jest pole ziemskie.Earth's field NMR imaging with use of spin and gradient ech

Społeczno-kulturowe postawy wobec własnego wyglądu i niezadowolenie z ciała u kobiet i mężczyzn w okresie późnej adolescencji: badania wstępne

Celem badań była analiza (1) społeczno-kulturowych postaw wobec własnego wyglądu (presji ze strony mediów oraz internalizacji ideału atletycznej sylwetki) i niezadowolenia z ciała oraz (2) współzależności pomiędzy presją mediów, internalizacją ideału atletycznej sylwetki, wskaźnikiem masy ciała a niezadowoleniem z własnego ciała u kobiet i mężczyzn w okresie późnej adolescencji. Badaniem objęto 34 kobiety i 30 mężczyzn w wieku między 17 a 19 rokiem życia. Zastosowano Kwestionariusz Postaw Społeczno-kulturowych wobec Wyglądu (Sociocultural Attitudes Towards Appearance Questionnaire 3; Thompson i in., 2004) oraz Test Sylwetek (Contour Drawing Rating Scale; Thompson, Gray, 1995). Badane kobiety przejawiały większe niezadowolenie z własnego ciała aniżeli mężczyźni oraz doświadczały silniejszej presji ze strony mediów w zakresie zmiany kształtu ciała, natomiast badani mężczyźni wykazywali większą internalizację ideału atletycznej sylwetki w porównaniu z kobietami. W grupie badanych kobiet istniała dodatnia zależność pomiędzy niezadowoleniem z ciała a doświadczaniem presji ze strony mediów w zakresie zmiany kształtu ciała. W obu badanych grupach zaobserwowano ponadto istnienie związku pomiędzy niezadowoleniem z ciała a wskaźnikiem masy ciała. Biorąc pod uwagę otrzymane wyniki, należy stworzyć efektywne programy zwiększenia świadomości w zakresie obrazu własnego ciała u osób w okresie późnej adolescencji

The value of magnetic resonance enterography in diagnostic difficulties associated with Crohn's disease

Purpose: The diagnosis of Crohn's disease (CD), one of the inflammatory bowel diseases (IBD), along with ulcerative colitis (UC), is often challenging due to the limitations of small intestine visualisation. Magnetic resonance enterography (MRE) enables imaging of intraluminal and extraintestinal complications without ionizing radiation. The objective of this study is to select CD-related MRE features and determine the feasibility of this technique to indicate a group of patients that should be subjected to more invasive diagnostic procedures. Material and methods: A total of 131 patients (mean age 25) underwent MRE, 60 of whom had been previously diagnosed with CD and 17 with UC. Additionally, 26 patients with suspected IBD and 28 with other or unknown pathologies were included in the study. Radiological reports of MRE examinations, effectuated using a 1.5-T field strength, were retrospectively analysed regarding radiological features of IBD, such as the following: bowel wall thickening, enhancement, comb sign, stricture, enlarged mesenteric nodes, inflammatory infiltration, and abnormal diffusion restriction in diffusion-weighted imaging. The statistical model was based on machine learning of the Kohonen map, together with univariate and multivariate analysis. Results: The selected neuron (Neuron 3) incorporated 23 cases of CD, 9 of suspected IBD, 2 patients with UC, and 4 with other pathologies. The statistical analysis identified bowel wall thickening, intestinal stricture, and lymphadenopathy as the 3 MRE findings most associated with Neuron 3 (AUC = 0.919, p = 0.031). Conclusions: Bowel wall thickening, stricture, and enlarged mesenteric lymph nodes in MRE are independent predictive factors for CD diagnosis; thus, patients presenting these features should undergo further examinations. MRE constitutes a powerful imaging modality in cases of suspected IBD

The Degradation Product of Ramipril Is Potentially Carcinogenic, Genotoxic and Mutagenic

(1) Background: The aim of this study was to identify the degradation product of ramipril (RAM) formed under dry air and to verify its potential modes of carcinogenicity. We intended to check whether its formation and presence in final dosage forms could pose a cancer risk to humans who are treated with RAM due to cardiological indications. The carcinogenicity of this compound was evaluated with respect to two mechanisms: a potential direct DNA-damage and indirect toxicity, secondary to forming mutagenic N-nitroso metabolites. (2) Methods: Firstly, a forced ageing test under dry air was conducted for pure RAM in order to induce its degradation. The validated HPLC system was used to describe the kinetic order of this reaction. The emerging degradation impurity was identified by HPLC-MS. In the second stage, the cancer risk of the identified RAM degradant was predicted using a structure-based assessment by in silico QSAR model, employing three endpoints: carcinogenicity, genotoxicity and mutagenicity. In the third stage, the obtained QSAR results were experimentally verified. To verify genotoxicity prediction, in vitro micronucleus assay was employed. It enabled us to assess the potential direct DNA-damaging properties of RAM degradant at high concentrations (as screening series) and at concentrations usually observed in human blood (to mimic the clinical scenario). To verify the QSAR mutagenicity prediction, an in vitro Ames test was carried out. It was designed so as to detect two mechanisms of mutagenicity: a direct one (for pure degradant) and an indirect one (via N-nitroso-metabolites formation). N-nitroso-metabolites for mutagenicity assessment were obtained using NAP test. (3) Results: The kinetic mechanism of RAM degradation was first-order, the degradation rate constant was k = 1.396 ± 0.133 × 10−5 s−1 (T = 373 K), thus the formation of impurity was rapid. Energy of activation was 174.12 ± 46.2 kJ/mol, entropy was positive, thus reaction was bimolecular and favored; enthalpy was 171.65 ± 48.7 kJ/mol, thus reaction was endothermic. Only one degradation impurity was formed, and it was identified as RAM diketopiperazine derivative (DKP). QSAR simulation predicted that DKP could be carcinogenic and genotoxic, but this result had only moderate reliability. DKP was also predicted to be non-mutagenic and this prediction was strong (endpoint score 0.2). The confirmatory micronucleus experiment for genotoxicity prediction suggested that DKP was cytotoxic and it could be also aneugenic at a high concentration (0.22 mg/mL), evidenced by a three-fold increase in micronuclei relative to the control (11.86:33.33%, p = 0.0184). At physiologic concentrations, its cytotoxicity and genotoxicity did not occur. This means that the genotoxicity of DKP was limited by a threshold mechanism. In the mutagenicity in vitro assessment, pure DKP was not mutagenic, but its nitrosation product induced base substitutions mutations in test bacteria TA100 following metabolic activation at a concentration of 4.5 mg/mL, confirming its mutagenicity. (4) Conclusions: RAM rapidly cyclizes to diketopiperazine derivative under dry air. This impurity resides in drugs administered to patients. DKP is potentially aneugenic and cytotoxic at high concentrations, yet at concentrations typically occurring in human blood, this effect is unlikely. The exposure of patients to high concentrations of DKP, exceeding the typical blood level and standard RAM dosing, could lead to cancer development, thus the safe threshold for human exposure to DKP must be verified in follow-up in vivo experiments. Based on our results, it is impossible to establish the maximum safe dose of pure DKP to humans. Furthermore, DKP itself is not mutagenic, but it is liable to the formation of mutagenic nitroso-metabolites in vivo. Nitroso-derivatives of DKP are in vitro mutagens and their real-life impact on humans must be further evaluated in in vivo studies. Until this is carried out, RAM should not be formulated by manufacturers using dry procedures to minimize DKP formation and reduce risk of human carcinogenesis, since DKP could cause cancer via two independent mechanisms: direct genotoxicity when the exposure over standard RAM dosing occurs, and indirect mutagenicity via in vivo N-nitrosamine formation

Refugees unwelcome:Narcissistic and secure national commitment differentially predict collective action against immigrants and refugees

Funding information: The preparation of this paper was supported by the National Science Centre Poland Opus grant (UMO-2017/25/B/HS6/01116) and Harmonia grant (UMO-2017/26/M/HS6/00689) conferred to the first author as well as the German Federal Ministry of Education and Research grant (01UL1816X) conferred to the fifth author.Two studies (N1 = 193; N2 = 598) were conducted in Poland to examine the role of two types of ingroup commitment (i.e., national narcissism and national identification) as predictors of atti-tudes towards immigrants and refugees (disadvantaged groups) and intentions to engage in collective action against them. As predicted, national narcissism (but not national identification) was related to more hostile intergroup attitudes and greater willingness to engage in collective action against refugees and immigrants. The positive effect of national narcissism on intentions to engage in collective action against immigrants and refugees was mediated by attitudes towards those groups. These results show that applying a more fine-grained approach to ingroup commitment (e.g., national narcissism vs. national identification) among advantaged group members allows for a better understanding of their intergroup attitudes and behavioral intentions to actively oppose the rights of disadvantaged social groups via collective action.PostprintPeer reviewe

Refugees unwelcome:narcissistic and secure national commitment differentially predict collective action against immigrants and refugees

Two studies (N1 = 193; N2 = 598) were conducted in Poland to examine the role of two types of ingroup commitment (i.e., national narcissism and national identification) as predictors of atti-tudes towards immigrants and refugees (disadvantaged groups) and intentions to engage in collective action against them. As predicted, national narcissism (but not national identification) was related to more hostile intergroup attitudes and greater willingness to engage in collective action against refugees and immigrants. The positive effect of national narcissism on intentions to engage in collective action against immigrants and refugees was mediated by attitudes towards those groups. These results show that applying a more fine-grained approach to ingroup commitment (e.g., national narcissism vs. national identification) among advantaged group members allows for a better understanding of their intergroup attitudes and behavioral intentions to actively oppose the rights of disadvantaged social groups via collective action.</p