Active biloma and the use of hepatobiliary specific MR contrast agent.

We present a case of a woman in her 70s, with right upper quadrant pain and jaundice, who underwent laparoscopic cholecystectomy 14 days, previously. The ultrasound and computer tomography scan revealed a fluid lesion in the gallbladder fossa with intrahepatic extension. At this point a wide differential diagnosis was possible. In order to reach a definitive diagnosis, a magnetic resonance imaging exam with a biliary excretion contrast agent - gadoxetate disodium (hepatobiliary specific paramagnetic gadolinium-based contrast) was obtained, which showed a lesion with delayed, but important contrast enhancement, 4 hours after contrast injection, demonstrating leaking of bile reaching the final diagnosis of biloma. Our patient was successfully treated with ultrasound-guided percutaneous drainage.

Serine ubiquitination of SQSTM1 regulates NFE2L2-dependent redox homeostasis.

The KEAP1-NFE2L2 axis is essential for the cellular response against metabolic and oxidative stress. KEAP1 is an adaptor protein of CUL3 (cullin 3) ubiquitin ligase that controls the cellular levels of NFE2L2, a critical transcription factor of several cytoprotective genes. Oxidative stress, defective autophagy and pathogenic infections activate NFE2L2 signaling through phosphorylation of the autophagy receptor protein SQSTM1, which competes with NFE2L2 for binding to KEAP1. Here we show that phosphoribosyl-linked serine ubiquitination of SQSTM1 catalyzed by SidE effectors of Legionella pneumophila controls NFE2L2 signaling and cell metabolism upon Legionella infection. Serine ubiquitination of SQSTM1 sterically blocks its binding to KEAP1, resulting in NFE2L2 ubiquitination and degradation. This reduces NFE2L2-dependent antioxidant synthesis in the early phase of infection. Levels of serine ubiquitinated SQSTM1 diminish in the later stage of infection allowing the expression of NFE2L2-target genes; causing a differential regulation of the host metabolome and proteome in a NFE2L2-dependent manner.Abbreviation: ARE: antioxidant response element; Dup: deubiquitinase specific for phosphoribosyl-linked serine ubiquitination; ER: endoplasmic reticulum; h.p.i: hours post infection; HIF1A/HIF-1α: hypoxia inducible factor 1 subunit alpha; KEAP1: kelch like ECH associated protein 1; KIR: KEAP1-interacting region; LIR: LC3-interacting region; NES: nuclear export signal; NFKB/NF-κB: nuclear factor kappa B; NLS: nuclear localization signal; NFE2L2/Nrf2: NFE2 like bZIP transcription factor 2; PB1 domain: Phox1 and Bem1 domain; PR-Ub: phosphoribosyl-linked serine ubiquitination; ROS: reactive oxygen species; SQSTM1/p62: sequestosome 1; tBHQ: tertiary butylhydroquinone; TUBE2: tandem ubiquitiin binding entity 2; UBA domain: ubiquitin-associated domain.

The aryl hydrocarbon receptor and FOS mediate cytotoxicity induced by Acinetobacter baumannii.

Acinetobacter baumannii is a pathogenic and multidrug-resistant Gram-negative bacterium that causes severe nosocomial infections. To better understand the mechanism of pathogenesis, we compare the proteomes of uninfected and infected human cells, revealing that transcription factor FOS is the host protein most strongly induced by A. baumannii infection. Pharmacological inhibition of FOS reduces the cytotoxicity of A. baumannii in cell-based models, and similar results are also observed in a mouse infection model. A. baumannii outer membrane vesicles (OMVs) are shown to activate the aryl hydrocarbon receptor (AHR) of host cells by inducing the host enzyme tryptophan-2,3-dioxygenase (TDO), producing the ligand kynurenine, which binds AHR. Following ligand binding, AHR is a direct transcriptional activator of the FOS gene. We propose that A. baumannii infection impacts the host tryptophan metabolism and promotes AHR- and FOS-mediated cytotoxicity of infected cells.

Exploring Limit Cycles of Differential Equations through Information Geometry Unveils the Solution to Hilbert's 16th Problem.

The detection of limit cycles of differential equations poses a challenge due to the type of the nonlinear system, the regime of interest, and the broader context of applicable models. Consequently, attempts to solve Hilbert's sixteenth problem on the maximum number of limit cycles of polynomial differential equations have been uniformly unsuccessful due to failing results and their lack of consistency. Here, the answer to this problem is finally obtained through information geometry, in which the Riemannian metrical structure of the parameter space of differential equations is investigated with the aid of the Fisher information metric and its scalar curvature R. We find that the total number of divergences of |R| to infinity provides the maximum number of limit cycles of differential equations. Additionally, we demonstrate that real polynomial systems of degree n≥2 have the maximum number of 2(n-1)(4(n-1)-2) limit cycles. The research findings highlight the effectiveness of geometric methods in analyzing complex systems and offer valuable insights across information theory, applied mathematics, and nonlinear dynamics. These insights may pave the way for advancements in differential equations, presenting exciting opportunities for future developments.

Futile therapeutic nursing interventions in adult intensive care: A descriptive study.

Background: Despite the progress made in recent decades on the phenomenon of futility in adult intensive care, recognizing it during clinical care practice remains a complex and sensitive process, during which questions are often raised for which concrete answers are difficult to find. Aims: To analyze the frequency with which futile nursing interventions are implemented in critically ill patients admitted to adult intensive care in specific situations and how often futile autonomous and interdependent nursing interventions are implemented in the same population, as perceived by adult intensive care nurses. Research design: Cross-sectional, quantitative, and descriptive study, which employed a questionnaire constructed specifically for this research to assess the perception of therapeutic futility in nursing in adult intensive care. Following an evaluation of the psychometric properties, the questionnaire was made available in an electronic format on the EUSurvey platform between August and October 2024. The data was analyzed between November 2023 and March 2024 using the statistical software packages SPSS and R. Participants and research context: A simple random sample of nurses working in level II and level III intensive care units in Portugal. Ethical considerations: Research ethical approvals were obtained, and the participants provided informed consent. Findings/results: Four hundred and fourteen valid questionnaires were obtained. The results allow the identification of thirty-three statistically significant associations, the inference of intervals for the mean and median for the perception of futility of nursing interventions with a 95% confidence interval, and enable the hierarchization of nursing interventions implemented in critically ill patients admitted to adult intensive care units according to the nurses' perception of their futility. Conclusion: There is a balance in nurses' perception of the futility of their interventions in the specific situations analyzed. There is statistically significant evidence that interdependent nursing interventions are, in general, more frequently perceived as futile when compared to autonomous nursing interventions.

IL-2 family cytokines IL-9 and IL-21 differentially regulate innate and adaptive type 2 immunity in asthma.

BACKGROUND: Asthma is often accompanied by type 2 immunity rich in IL-4, IL-5, and IL-13 cytokines produced by TH2 lymphocytes or type 2 innate lymphoid cells (ILC2s). IL-2 family cytokines play a key role in the differentiation, homeostasis, and effector function of innate and adaptive lymphocytes. OBJECTIVE: IL-9 and IL-21 boost activation and proliferation of TH2 and ILC2s, but the relative importance and potential synergism between these γ common chain cytokines are currently unknown. METHODS: Using newly generated antibodies, we inhibited IL-9 and IL-21 alone or in combination in various murine models of asthma. In a translational approach using segmental allergen challenge, we recently described elevated IL-9 levels in human subjects with allergic asthma compared with nonasthmatic controls. Here, we also measured IL-21 in both groups. RESULTS: IL-9 played a central role in controlling innate IL-33-induced lung inflammation by promoting proliferation and activation of ILC2s in an IL-21-independent manner. Conversely, chronic house dust mite-induced airway inflammation, mainly driven by adaptive immunity, was solely dependent on IL-21, which controlled TH2 activation, eosinophilia, total serum IgE, and formation of tertiary lymphoid structures. In a model of innate on adaptive immunity driven by papain allergen, a clear synergy was found between both pathways, as combined anti-IL-9 or anti-IL-21 blockade was superior in reducing key asthma features. In human bronchoalveolar lavage samples we measured elevated IL-21 protein within the allergic asthmatic group compared with the allergic control group. We also found increased IL21R transcripts and predicted IL-21 ligand activity in various disease-associated cell subsets. CONCLUSIONS: IL-9 and IL-21 play important and nonredundant roles in allergic asthma by boosting ILC2s and TH2 cells, revealing a dual IL-9 and IL-21 targeting strategy as a new and testable approach.

Accessory liver lobe: an uncommon abdominal mass mimicker.

Heterotopic hepatic tissue is a rare development anomaly, exhibiting diverse forms and locations. We present a case report of an asymptomatic woman in her 40s who had an 8 cm mass in the left hypochondrium detected on routine ultrasound, which was initially suspected to be a tumour. Further investigation revealed that the mass had a similar enhancement to the liver on gadoxetate disodium-enhanced MRI and presented a connection with the original liver via vascular pedicle, favouring the diagnosis of accessory liver lobe (ALL). Accurate differentiation of ALL from other abdominal masses poses a diagnostic challenge, potentially leading to misdiagnosis of malignant tumours and unnecessary interventions. Although usually small and asymptomatic, rarely they can present with acute complications, and cross-sectional techniques play an important role in enabling early diagnosis and management. Therefore, radiologists must raise awareness regarding ALL, their imagological findings, and diagnostic pathways, and understand potential associated complications.

Body position and cuff size influence lower limb arterial occlusion pressure and its predictors: implications for standardizing the pressure applied in training with blood flow restriction.

Background: Arterial occlusion pressure (AOP) is a relevant measurement for individualized prescription of exercise with blood flow restriction (BFRE). Therefore, it is important to consider factors that may influence this measure. Purpose: This study aimed to compare lower limb AOP (LL-AOP) measured with 11 cm (medium) and 18 cm (large) cuffs, in different body positions, and explore the predictors for each of the LL-AOP measurements performed. This information may be useful for future studies that seek to develop approaches to improve the standardization of pressure adopted in BFRE, including proposals for equations to estimate LL-AOP. Methods: This is a cross-sectional study. Fifty-one healthy volunteers (males, n = 25, females, n = 26; Age: 18-40 years old) underwent measurement of thigh circumference (TC), brachial blood pressure, followed by assessments of LL-AOP with medium and large cuffs in positions supine, sitting and standing positions. Results: The large cuff required less external pressure (mmHg) to elicit arterial occlusion in all three-body positions when compared to the medium cuff (p < 0.001). The LL-AOP was significantly lower in the supine position, regardless of the cuff used (p < 0.001). Systolic blood pressure was the main predictor of LL-AOP in the large cuff, while TC was the main predictor of LL-AOP with the medium cuff. Body position influenced strength of the LL-AOP predictors. Conclusion: Our results indicate that LL-AOP and its predictors are substantially influenced by body position and cuff width. Therefore, these variables should be considered when standardizing the pressure prescribed in BFRE.

The Microenvironment of Solid Tumors: Components and Current Challenges of Tumor-on-a-Chip Models.

Solid tumors represent the most common type of cancer in humans and are classified into sarcomas, lymphomas, and carcinomas based on the originating cells. Among these, carcinomas, which arise from epithelial and glandular cells lining the body's tissues, are the most prevalent. Around the world, a significant increase in the incidence of solid tumors is observed during recent years. In this context, efforts to discover more effective cancer treatments have led to a deeper understanding of the tumor microenvironment (TME) and its components. Currently, the interactions between cancer cells and elements of the TME are being intensely investigated. Remarkable progress in research is noted, largely owing to the development of advanced in vitro models, such as tumor-on-a-chip models that assist in understanding and ultimately discovering new effective treatments for a specific type of cancer. The purpose of this article is to provide a review of the TME and cancer cell components, along with the advances on tumor-on-a-chip models designed to mimic tumors, offering a perspective on the current state of the art. Recent studies using this kind of microdevices that reproduce the TME have allowed a better understanding of the cancer and its treatments. Nevertheless, current applications of this technology present some limitations that must be overcome to achieve a broad application by researchers looking for a deeper knowledge of cancer and new strategies to improve current therapies.

Effects of different ischemic pressures on bar velocity during the bench press exercise: A randomized crossover trial.

The main objective of this study was to evaluate the effects of different ischemic pressures applied during rest intervals on bar velocity during the bench press exercise. 10 resistance-trained males (age = 23.2 ± 2.7 years; body mass = 83.9 ± 9 kg; body height = 181 ± 5.2 cm; bench press 1 repetition maximum (1RM) = 125 ± 16.4 kg; training experience = 5.4 ± 3.4 years) participated in the study. During 4 experimental sessions, following a randomized crossover design, the subjects performed 5 sets of 3 repetitions of the bench press exercise with a load of 60% 1RM under conditions: with ischemia (50% or 80% of arterial occlusion pressure), with SHAM ischemia (20 mmHg) and without ischemia (control condition). For the ischemic conditions cuffs were applied before each set for 6.5 min and released 30 s before the start of the set as reperfusion (6.5 min ischemia + 0.5 min reperfusion). In the control condition, ischemia was not applied. The two-way repeated measures ANOVA showed no significant condition × set interaction for mean bar velocity (MV; p = 0.17) and peak bar velocity (PV; p = 0.66). There was also no main effect of condition for MV (p = 0.58) and PV (p = 0.61). The results indicate that ischemic or SHAM treatment (6.5 minutes ischemia or SHAM + 30 s reperfusion) does not affect mean and peak bar velocity during the bench press exercise regardless of the applied pressure.

Nuclear magnetic resonance spectroscopy reveals biomarkers of stroke recovery in a mouse model of obesity-associated type 2 diabetes.

Obesity and Type 2 diabetes (T2D) are known to exacerbate cerebral injury caused by stroke. Metabolomics can provide signatures of metabolic disease, and now we explored whether the analysis of plasma metabolites carries biomarkers of how obesity and T2D impact post-stroke recovery. Male mice were fed a high-fat diet (HFD) for 10 months leading to development of obesity with T2D or a standard diet (non-diabetic mice). Then, mice were subjected to either transient middle cerebral artery occlusion (tMCAO) or sham surgery and allowed to recover on standard diet for 2 months before serum samples were collected. Nuclear magnetic resonance (NMR) spectroscopy of serum samples was used to investigate metabolite signals and metabolic pathways that were associated with tMCAO recovery in either T2D or non-diabetic mice. Overall, after post-stroke recovery there were different serum metabolite profiles in T2D and non-diabetic mice. In non-diabetic mice, which show full neurological recovery after stroke, we observed a reduction of isovalerate, and an increase of kynurenate, uridine monophosphate, gluconate and N6-acetyllysine in tMCAO relative to sham mice. In contrast, in mice with T2D, which show impaired stroke recovery, there was a reduction of N,N-dimethylglycine, succinate and proline, and an increase of 2-oxocaproate in serum of tMCAO versus sham mice. Given the inability of T2D mice to recover from stroke, in contrast with non-diabetic mice, we propose that these specific metabolite changes following tMCAO might be used as biomarkers of neurophysiological recovery after stroke in T2D.

The effect of complex contrast training with different training frequency on the physical performance of youth soccer players: a randomized study.

Background: Complex contrast training (CCT) is potentially an efficient method to improve physical abilities such as muscle strength, power output, speed, agility, are extremely important in developing soccer players of different age categories. Aim: This study aimed to analyze the effects of 6 weeks of CCT program applied in different training frequency (sessions per week) on youth soccer players performance. Methods: Twenty-one youth soccer players (age: 15.3 ± 1.1 years; body mass 64.9 ± 0.7 kg; height 175.4 ± 0.7 cm) were randomized into three groups: a regular pre-season training control group (G0, n = 8), a group with regular pre-season training plus twice-a-week CCT (G2, n = 6), and a group with regular pre-season training plus thrice-a-week CCT (G3, n = 7). The CCT consisted of soccer skills-based exercises distributed across five stations, to be performed before common regular practice during a 6-week pre-season period. The agility (505 Agility test), sprint (S5 and S15), jump (SJ and CMJ), and free kick speed (11 m from the goal) of the groups were analyzed pre- and post-CCT intervention. During a 6-week pre-season period, the players integrated CCT into their regular training sessions. Furthermore, performance variables were compared between the groups. Results: A statistical difference was identified for the timepoint for the players' CMJ (p = 0.023; η2 = 0.343) and the free kick speed (p = 0.013; η2 = 0.383) using ANOVA. The G3 showed a significant improvement in the CMJ (p = 0.001) and the free kick speed (p = 0.003) between pre- to post-CCT test. No other significant changes in performance were observed (p > 0.05). Conclusion: The CCT training program with a weekly frequency of 3 days per week is effective in improving free kick speed and CMJ performance in young male soccer players (U-15 and U-17 categories). CCT training programs have the potential to refine an athlete's preparation for competition. However, certain performance tests did not demonstrate substantial enhancements. Consequently, additional investigations are required to ascertain the effectiveness of CCT.

Resequencing of Brazilian locally adapted cattle breeds revealed variants in candidate genes and transcription factors for meat fatty acid profile.

The beef cattle industry has experienced a shift driven by a market demand for healthier meat, cost efficiency and environmental sustainability in recent years. Consequently, there has been a growing focus on the fatty acids content and functions of meat in cattle breeding programmes. Besides, a deeper understanding of the biological mechanisms influencing the expression of different phenotypes related to fatty acid profiles is crucial. In this study, we aimed to identify Single-Nucleotide Variants (SNV) and Insertion/Deletion (InDels) DNA variants in candidate genes related to fatty acid profiles described in genomic, transcriptomic and proteomic studies conducted in beef cattle breeds. Utilizing whole-genome re-sequencing data from Brazilian locally adapted bovine breeds, namely Caracu and Pantaneiro, we identified SNVs and InDels associated with 23,947 genes. From these, we identified 318 candidate genes related to fatty acid profiles that contain variants. Subsequently, we select only genes with SNVs and InDels in their promoter, 5' UTR and coding region. Through the gene-biological process network, approximately 19 genes were highlighted. Furthermore, considering the studied trait and a literature review, we selected the main transcription factors (TF). Functional analysis via gene-TF network allowed us to identify the 30 most likely candidate genes for meat fatty acid profile in cattle. LIPE, MFSD2A and SREBF1 genes were highlighted in networks due to their biological importance. Further dissection of these genes revealed 15 new variants found in promoter regions of Caracu and Pantaneiro sequences. The gene networks facilitated a better functional understanding of genes and TF, enabling the identification of variants potentially related to the expression of candidate genes for meat fatty acid profiles in cattle.

Evaluating performance on the Glittre-ADL test in men with long COVID 3 years after a SARS-CoV-2 infection.

Background/objective: Many COVID-19 survivors, especially those who have been hospitalized, have been suffering numerous complications that limit their activities of daily living, although changes that persist 3 years after infection are still not known. We aimed to investigate the impact of long COVID on the Glittre-ADL test (TGlittre) 3 years after acute infection in men who needed hospitalization and explore whether the performance on the TGlittre is associated with impairments in lung function, muscle strength, physical function and quality of life (QoL). Methods: Cross-sectional study with 42 men with long COVID who took the TGlittre. They underwent pulmonary function tests and measurements of handgrip strength and quadriceps strength (QS). Additionally, they also completed the Saint George Respiratory Questionnaire (SGRQ) and Functional Independence Measure (FIM). Results: The mean age was 52 ± 10.6 years, while the mean time after diagnosis of COVID-19 was 37 ± 3.5 months. The mean TGlittre time was 3.3 (3.1-4.1) min, which was 10% greater than the time expected for normal individuals to complete it. The TGlittre time was correlated significantly with the QS (rs = -0.397, p = 0.009), pulmonary diffusion (rs = - 0.364, p = 0.017), FIM (rs = -0.364, p = 0.017) and the "activity" domain score of the SGRQ (rs = 0.327, p = 0.034). Conclusion: Functional capacity on exertion as measured by the TGlittre time is normal in most men with long COVID 3 years after hospitalization. However, this improvement in functional capacity does not seem to be reflected in muscle strength or QoL, requiring continued monitoring even after 3 years.

Selection, engineering, and in vivo testing of a human leukocyte antigen-independent T-cell receptor recognizing human mesothelin.

BACKGROUND: Canonical α/ß T-cell receptors (TCRs) bind to human leukocyte antigen (HLA) displaying antigenic peptides to elicit T cell-mediated cytotoxicity. TCR-engineered T-cell immunotherapies targeting cancer-specific peptide-HLA complexes (pHLA) are generating exciting clinical responses, but owing to HLA restriction they are only able to target a subset of antigen-positive patients. More recently, evidence has been published indicating that naturally occurring α/ß TCRs can target cell surface proteins other than pHLA, which would address the challenges of HLA restriction. In this proof-of-concept study, we sought to identify and engineer so-called HLA-independent TCRs (HiTs) against the tumor-associated antigen mesothelin. METHODS: Using phage display, we identified a HiT that bound well to mesothelin, which when expressed in primary T cells, caused activation and cytotoxicity. We subsequently engineered this HiT to modulate the T-cell response to varying levels of mesothelin on the cell surface. RESULTS: The isolated HiT shows cytotoxic activity and demonstrates killing of both mesothelin-expressing cell lines and patient-derived xenograft models. Additionally, we demonstrated that HiT-transduced T cells do not require CD4 or CD8 co-receptors and, unlike a TCR fusion construct, are not inhibited by soluble mesothelin. Finally, we showed that HiT-transduced T cells are highly efficacious in vivo, completely eradicating xenografted human solid tumors. CONCLUSION: HiTs can be isolated from fully human TCR-displaying phage libraries against cell surface-expressed antigens. HiTs are able to fully activate primary T cells both in vivo and in vitro. HiTs may enable the efficacy seen with pHLA-targeting TCRs in solid tumors to be translated to cell surface antigens.

Prediction models for physical function in COVID-19 survivors.

BACKGROUND: The burden of caring for patients who have survived COVID-19 will be enormous in the coming years, especially with respect to physical function. Physical function has been routinely assessed using the Post-COVID-19 Functional Status (PCFS) scale. AIM: This study built prediction models for the PCFS scale using sociodemographic data, clinical findings, lung function, and muscle strength. METHOD: Two hundred and one patients with post-COVID-19 syndrome (PCS) completed the PCFS scale to assess physical function. Their levels of general fatigue were also assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale, handgrip strength (HGS), and spirometry. RESULTS: The number of participants who scored 0 (none), 1 (negligible), 2 (slight), 3 (moderate), and 4 (severe) on the PCFS scale was 25 (12%), 40 (20%), 39 (19%), 49 (24%), and 48 (24%), respectively. The PCFS scale was significantly correlated with the following variables: FACIT-F score (r = -0.424, P < 0.001), HGS (r = -0.339, P < 0.001), previous hospitalization (r = 0.226, P = 0.001), body mass index (r = 0.163, P = 0.021), and sex (r = -0.153, P = 0.030). The regression model with the highest coefficient of regression (R = 0.559) included the following variables: age, sex, body mass index, FACIT-F, HGS, and previous hospitalization. CONCLUSIONS: Worse general fatigue and HGS are associated with more severe physical function impairments in PCS patients. Furthermore, a history of prior hospitalization results in worse physical function. Thus, prediction models for the PCFS scale that incorporate objective measures enable a better assessment of the physical function of these patients, thus helping in the selection of candidates for a program of physical reconditioning.

How young radiologists use contrast media and manage adverse reactions: an international survey.

OBJECTIVES: To collect real-world data about the knowledge and self-perception of young radiologists concerning the use of contrast media (CM) and the management of adverse drug reactions (ADR). METHODS: A survey (29 questions) was distributed to residents and board-certified radiologists younger than 40 years to investigate the current international situation in young radiology community regarding CM and ADRs. Descriptive statistics analysis was performed. RESULTS: Out of 454 respondents from 48 countries (mean age: 31.7 ± 4 years, range 25-39), 271 (59.7%) were radiology residents and 183 (40.3%) were board-certified radiologists. The majority (349, 76.5%) felt they were adequately informed regarding the use of CM. However, only 141 (31.1%) received specific training on the use of CM and 82 (18.1%) about management ADR during their residency. Although 266 (58.6%) knew safety protocols for handling ADR, 69.6% (316) lacked confidence in their ability to manage CM-induced ADRs and 95.8% (435) expressed a desire to enhance their understanding of CM use and handling of CM-induced ADRs. Nearly 300 respondents (297; 65.4%) were aware of the benefits of contrast-enhanced ultrasound, but 249 (54.8%) of participants did not perform it. The preferred CM injection strategy in CT parenchymal examination and CT angiography examination was based on patient's lean body weight in 318 (70.0%) and 160 (35.2%), a predeterminate fixed amount in 79 (17.4%) and 116 (25.6%), iodine delivery rate in 26 (5.7%) and 122 (26.9%), and scan time in 31 (6.8%) and 56 (12.3%), respectively. CONCLUSION: Training in CM use and management ADR should be implemented in the training of radiology residents. CRITICAL RELEVANCE STATEMENT: We highlight the need for improvement in the education of young radiologists regarding contrast media; more attention from residency programs and scientific societies should be focused on training about contrast media use and the management of adverse drug reactions. KEY POINTS: • This survey investigated training of young radiologists about use of contrast media and management adverse reactions. • Most young radiologists claimed they did not receive dedicated training. • An extreme heterogeneity of responses was observed about contrast media indications/contraindications and injection strategy.

Pharmacokinetics, biodistribution, and in vivo toxicity of 7-nitroindazole loaded in pegylated and non-pegylated nanoemulsions in rats.

Sepsis is a life-threatening condition caused by a dysregulated host response to infection. The development of sepsis is associated with excessive nitric oxide (NO) production, which plays an important role in controlling vascular homeostasis. 7-nitroindazole (7-NI) is a selective inhibitor of neuronal nitric oxide synthase (NOS-1) with potential application for treating NO imbalance conditions. However, 7-NI exhibits a low aqueous solubility and a short plasma half-life. To circumvent these biopharmaceutical limitations, pegylated (NEPEG7NI) and non-pegylated nanoemulsions (NENPEG7NI) containing 7-NI were developed. This study evaluates the pharmacokinetic profiles and toxicological properties of 7-NI loaded into the nanoemulsions. After a single intravenous administration of the free drug and the nanoemulsions at a dose of 10 mg.kg-1 in Wistar rats, 7-NI was widely distributed in the organs. The pharmacokinetic parameters of Cmax, t1/2, and AUC0-t were significantly increased after administration of the NEPEG7NI, compared to both free 7-NI and NENPEG7NI (p < 0.05). No observable adverse effects were observed after administering the free 7-NI, NEPEG7NI, or NENPEG7NI in the animals after a single dose of up to 3.0 mg.kg-1. The results indicated that 7-NI-loaded nanoemulsions are safe, constituting a promising approach to treating sepsis.

Density of Sphingosine-1-Phosphate Receptors Is Altered in Cortical Nerve-Terminals of Insulin-Resistant Goto-Kakizaki Rats and Diet-Induced Obese Mice.

Sphingosine-1-phosphate (S1P) is a phosphosphingolipid with pleiotropic biological functions. S1P acts as an intracellular second messenger, as well as extracellular ligand to five G-protein coupled receptors (S1PR1-5). In the brain, S1P regulates neuronal proliferation, apoptosis, synaptic activity and neuroglia activation. Moreover, S1P metabolism alterations have been reported in neurodegenerative disorders. We have previously reported that S1PRs are present in nerve terminals, exhibiting distinct sub-synaptic localization and neuromodulation actions. Since type 2 diabetes (T2D) causes synaptic dysfunction, we hypothesized that S1P signaling is modified in nerve terminals. In this study, we determined the density of S1PRs in cortical synaptosomes from insulin-resistant Goto-Kakizaki (GK) rats and Wistar controls, and from mice fed a high-fat diet (HFD) and low-fat-fed controls. Relative to their controls, GK rats showed similar cortical S1P concentration despite higher S1P levels in plasma, yet lower density of S1PR1, S1PR2 and S1PR4 in nerve-terminal-enriched membranes. HFD-fed mice exhibited increased plasma and cortical concentrations of S1P, and decreased density of S1PR1 and S1PR4. These findings point towards altered S1P signaling in synapses of insulin resistance and diet-induced obesity models, suggesting a role of S1P signaling in T2D-associated synaptic dysfunction.

Long-term trends in juvenile Mugil liza abundance in relation to selected environmental and fisheries influences in southern Brazil.

Overfishing constitutes a major threat affecting marine fish population worldwide, including mullet species that have been exploited by fisheries during the reproductive migration in temperate and tropical latitudes for millennia. In the present study, we investigated the relationship of fishing intensity of mullet Mugil liza during its reproductive migration and the abundance of their juveniles in an essential nursery ground for the species in the southwest Atlantic Ocean. To carry out this analysis, we used a 23-year standardized long-term time series (1997-2019) of monthly abundance of M. liza juveniles, local/regional (water temperature, salinity, water transparency and river discharge) and global (ENSO) environmental factors, along with compilations of fishing landing data for the species. Generalized Additive Models (GAM) revealed the negative effect of fishing adult populations on the abundance of juveniles when they reach the marine surf-zone and after recruiting into the estuary. Our results reinforce the importance of adequate conservation and fishery regulation policies to prevent the species' stock from collapsing.