Animal Welfare in Radiation Research: The Importance of Animal Monitoring System.

Long-term research into radiation exposure significantly expanded following World War II, driven by the increasing number of individuals falling ill after the detonation of two atomic bombs in Japan. Consequently, researchers intensified their efforts to investigate radiation's effects using animal models and to study disease models that emerged post-catastrophe. As a result, several parameters have been established as essential in these models, encompassing radiation doses, regimens involving single or multiple irradiations, the injection site for transplantation, and the quantity of cells to be injected. Nonetheless, researchers have observed numerous side effects in irradiated animals, prompting the development of scoring systems to monitor these animals' well-being. The aim of this review is to delve into the historical context of using animals in radiation research and explore the ethical considerations related to animal welfare, which has become an increasingly relevant topic in recent years. These concerns have prompted research groups to adopt measures aimed at reducing animal suffering. Consequently, for animal welfare, the implementation of a scoring system for clinical and behavioral monitoring is essential. This represents one of the primary challenges and hurdles in radiation studies. It is concluded that implementing standardized criteria across all institutions is aimed at ensuring result reproducibility and fostering collaboration within the scientific community.

Evaluation of urinary cysteinyl leukotrienes as biomarkers of severity and putative therapeutic targets in COVID-19 patients.

BACKGROUND: Cysteinyl leukotrienes (CysLT) are potent inflammation-promoting mediators, but remain scarcely explored in COVID-19. We evaluated urinary CysLT (U-CysLT) relationship with disease severity and their usefulness for prognostication in hospitalized COVID-19 patients. The impact on U-CysLT of veno-venous extracorporeal membrane oxygenation (VV-ECMO) and of comorbidities such as hypertension and obesity was also assessed. METHODS: Blood and spot urine were collected in "severe" (n = 26), "critically ill" (n = 17) and "critically ill on VV-ECMO" (n = 17) patients with COVID-19 at days 1-2 (admission), 3-4, 5-8 and weekly thereafter, and in controls (n = 23) at a single time point. U-CysLT were measured by ELISA. Routine markers, prognostic scores and outcomes were also evaluated. RESULTS: U-CysLT did not differ between groups at admission, but significantly increased along hospitalization only in critical groups, being markedly higher in VV-ECMO patients, especially in hypertensives. U-CysLT values during the first week were positively associated with ICU and total hospital length of stay in critical groups and showed acceptable area under curve (AUC) for prediction of 30-day mortality (AUC: 0.734, p = 0.001) among all patients. CONCLUSIONS: U-CysLT increase during hospitalization in critical COVID-19 patients, especially in hypertensives on VV-ECMO. U-CysLT association with severe outcomes suggests their usefulness for prognostication and as therapeutic targets.

Incidência da síndrome de liberação de citocinas nos transplantes de células-tronco hematopoéticas haploidêntico: um estudo retrospectivo / Incidence of Cytokine Release Syndrome in Haploidentical Hematopoietic Stem Cell Transplantation: a retrospective study

O transplante de células-tronco hematopoiéticas é uma modalidade de tratamento que consiste na infusão de células precursoras hematopoiéticas indiferenciadas (célulastronco) capazes de reconstituir a medula óssea previamente condicionada pela quimioterapia e/ou radioterapia e, posteriormente, normalizar a produção dos elementos do sangue. Esta terapia é utilizada, principalmente, para o tratamento de doenças hematológicas malignas ou benignas. De todas as fontes de células potenciais para o transplante alogênico de células-tronco hematopoéticas, o doador HLA aparentado totalmente compatível continua contribuindo para as melhores taxas de sobrevida global e livre de progressão. Entretanto, apenas 25-30% dos pacientes apresentam um doador HLA idêntico. Neste sentido que, há algumas décadas, a utilização de um doador aparentado/não aparentado parcialmente compatível (haploidêntico) tornou-se uma forte alternativa e seu uso vem crescendo exponencialmente. Uma das complicações relacionadas a essa terapia é a Síndrome de Liberação de Citocinas (SLC), que caracteriza-se pela liberação de citocinas inflamatórias geradas por linfócitos ativados e células inatas no contexto da terapia celular. Procurando um melhor entendimento da SLC no contexto do transplante haploidêntico, esse trabalho buscou analisar os fatores predisponentes, além do tratamento instituído e o desfecho desses pacientes, auxiliando na caracterização dessa entidade, ainda pouco estudada. Foi desenvolvido, então, um estudo retrospectivo a partir da análise dos prontuários médicos de todos os pacientes submetidos ao transplante haploidêntico no Centro de Transplante de Medula Óssea (CEMO) do Instituto Nacional de Câncer (INCA) de junho de 2013 a setembro de 2021. Nesse trabalho, analisamos 56 pacientes, com exclusão de 9 deles, por tratar-se de segundo transplante alogênico. Desses observamos que 15 pacientes (31,9%) cursaram com SLC. O gênero masculino foi o mais afetado e a faixa etária mais acometida foi entre 19 e 40 anos. A divergência de tipos sanguíneos, parece influenciar na apresentação mais grave da doença (10,6%) e no follow-up desses pacientes, os 5 casos que apresentaram o escore mais elevado faleceram logo após o transplante, enquanto os que apresentaram um escore baixo estão em remissão (8,5%). A SLC é uma complicação importante no TCTH-Haplo e frequentemente observada nos pacientes que receberam infusão de sangue periférico. Dessa forma, a prevenção da SLC deve ser objeto de futuras investigações em pacientes submetidos ao TCTH-Haplo, buscando um desfecho cada vez mais satisfatório

Hematopoietic stem cell transplantation is a treatment modality that consists on the infusion of undifferentiated hematopoietic precursor cells (stem cells) capable of reconstituting the bone marrow previously conditioned by chemotherapy and/or radiotherapy and, subsequently, normalizing the production of the elements of the blood. This therapy is mainly used for the treatment of malignant or benign hematological diseases. Of all potential cell sources for allogeneic hematopoietic stem cell transplantation, the fully matched HLA related donor continues to contribute to the best overall and progression-free survival rates. However, only 25-30% of patients have an HLA-identical donor. In this sense, a few decades ago, the use of a partially compatible (haploidentical) related/unrelated donor became a strong alternative and its use has been growing exponentially. One of the complications related to this therapy is the Cytokine Release Syndrome (CLS), which is characterized by the release of inflammatory cytokines generated by activated lymphocytes and innate cells in the context of cell therapy. Looking for a better understanding of CLS in the context of haploidentical transplantation, this study sought to analyze the predisposing factors, in addition to the treatment instituted and the outcome of these patients, helping to characterize this entity, which is still little known. A retrospective study was then developed based on the analysis of the medical records of all patients undergoing haploidentical transplantation at the Bone Marrow Transplant Center (CEMO) of the National Cancer Institute (INCA) from June 2013 to September 2021. In this study, we analyzed 56 patients, excluding 9 of them, as it was a second allogeneic transplant. Of these, we observed that 15 patients (31.9%) had CLS. The male gender was the most affected and the age group most affected was between 19 and 40 years old. The divergence of blood types seems to influence the more severe presentation of the disease (10.6%) and the follow-up of these patients showed that the 5 cases whom presented the highest score of the disease died shortly after the transplant, while those that presented a low score are still in remission (8.5%). CLS is an important complication in Haplo-HSCT and is frequently seen in patients receiving peripheral blood infusion. Thus, the prevention of CLS should be the subject of future investigations in patients undergoing Haplo-HSCT, seeking an increasingly satisfactory outcome

Can Psychologic Stress Elevate Intraocular Pressure in Healthy Individuals?

PURPOSE: To investigate if a stress event can influence intraocular pressure (IOP) in a group of healthy individuals. DESIGN: Case-control study. PARTICIPANTS: A total of 28 healthy subjects were included: 17 in the stress group and 11 in the control group. METHODS: The Trier Social Stress Test (TSST) is a tool to evaluate cortisol response to psychologic stimulation based on the stress induced by public speaking. All participants underwent a modified diurnal tension curve (DTC) 1 week before the TSST, with 3 IOP measurements performed between 8:00 am and 2:00 pm. We evaluated the response to the TSST measuring the levels of salivary cortisol, IOP, and heart rate before, immediately after, and 40 minutes after TSST. The State Trait Anxiety Inventory (STAI) was applied to evaluate the levels of anxiety at the same time intervals. MAIN OUTCOME MEASURES: Changes in IOP (mmHg), salivary cortisol, heart rate, and STAI scores. RESULTS: At baseline, there were no significant differences between case and controls regarding age (52.2 ± 6.26 vs. 53.8 ± 8.4 years, P = 0.661), gender (52.94% male vs. 45.45% female, P = 0.669), and ethnicity. Salivary cortisol (6.8 nmol/l, P < 0.001) and heart rate (7.2 beats/min, P = 0.035) increased significantly after the TSST. We observed a mean IOP increase of 1.0 mmHg (right eye, P = 0.003) and 1.1 mmHg (left eye, P = 0.004) when comparing IOP measurements obtained during the DTC and immediately after TSST. In addition, 35% (6/17) of the subjects in the TSST group showed an IOP increase higher than 2 mmHg after the test compared with 18% (2/11) in the control group. The STAI state score significantly increased after the stress event compared with baseline (P = 0.026) and decreased from poststress to the recovery period (P = 0.006) in the TSST group. The control group did not show significant changes in IOP, heart rate, salivary cortisol levels, and STAI scores. CONCLUSIONS: Significant elevations of IOP, salivary cortisol, STAI scores, and heart rate occurred after inducing psychologic stress with TSST in a group of healthy individuals.

Holistic word context does not influence holistic processing of artificial objects in an interleaved composite task.

Holistic processing, a hallmark of expert processing, has been shown for written words, signaled by the word composite effect, similar to the face composite effect: fluent readers find it difficult to focus on just one half of a written word while ignoring the other half, especially when the two word halves are aligned rather than misaligned. This effect is signaled by a significant interaction between alignment and congruency of the two word parts. Face and visual word recognition, however, involve different neural mechanisms with an opposite hemispheric lateralization. It is then possible that faces and words can both involve holistic processing in their own separate face and word processing systems, but by using different mechanisms. In the present study, we replicated with words a previous study done with faces (Richler, Bukach, & Gauthier, 2009, Experiment 3). In a first experiment we showed that in a composite task with aligned artificial objects, no congruency effects are found. In a second experiment, using an interleaved task, a congruency effect for Ziggerins was induced in trials in which a word was first encoded, but more strongly when it was aligned. However, in a stricter test, we found no differences between the congruency effect for Ziggerins induced by aligned words versus pseudowords. Our results demonstrate that different mechanisms can underlie holistic processing in different expertise domains.

Sequential morphological characteristics of murine fetal liver hematopoietic microenvironment in Swiss Webster mice.

Embryonic hematopoiesis occurs via dynamic development with cells migrating into various organs. Fetal liver is the main hematopoietic organ responsible for hematopoietic cell expansion during embryologic development. We describe the morphological sequential characteristics of murine fetal liver niches that favor the settlement and migration of hematopoietic cells from 12 days post-coitum (dpc) to 0 day post-partum. Liver sections were stained with hematoxylin and eosin, Lennert's Giemsa, Sirius Red pH 10.2, Gomori's Reticulin, and Periodic Acid Schiff/Alcian Blue pH 1.0 and pH 2.5 and were analyzed by bright-field microscopy. Indirect imunohistochemistry for fibronectin, matrix metalloproteinase-1 (MMP-1), and MMP-9 and histochemistry for naphthol AS-D chloroacetate esterase (NCAE) were analyzed by confocal microscopy. The results showed that fibronectin was related to the promotion of hepatocyte and trabecular differentiation; reticular fibers did not appear to participate in fetal hematopoiesis but contributed to the physical support of the liver after 18 dpc. During the immature phase, hepatocytes acted as the fundamental stroma for the erythroid lineage. The appearance of myeloid cells in the liver was related to perivascular and subcapsular collagen, and NCAE preceded MMP-1 expression in neutrophils, an occurrence that appeared to contribute to their liver evasion. Thus, the murine fetal liver during ontogenesis shows two different phases: one immature and mainly endodermic (<14 dpc) and the other more developed (endodermic-mesenchymal; >15 dpc) with the maturation of hepatocytes, a better definition of trabecular pattern, and an increase in the connective tissue in the capsule, portal spaces, and liver parenchyma. The decrease of hepatic hematopoiesis (migration) coincides with hepatic maturation.