Post-Mortem Immunohistochemical Evidence of β2-Adrenergic Receptor Expression in the Adrenal Gland

The evidence from post-mortem biochemical studies conducted on cortisol and catecholamines suggest that analysis of the adrenal gland could provide useful information about its role in human pathophysiology and the stress response. Authors designed an immunohistochemical study on the expression of the adrenal β2-adrenergic receptor (β2-AR), a receptor with high-affinity for catecholamines, with the aim to show which zones it is expressed in and how its expression differs in relation to the cause of death. The immunohistochemical study was performed on adrenal glands obtained from 48 forensic autopsies of subjects that died as a result of different pathogenic mechanisms using a mouse monoclonal β2-AR antibody. The results show that immunoreactivity for β2-AR was observed in all adrenal zones. Furthermore, immunoreactivity for β2-AR has shown variation in the localization and intensity of different patterns in relation to the original cause of death. To the best of our knowledge, this is the first study that demonstrates β2-AR expression in the human cortex and provides suggestions on the possible involvement of β2-AR in human cortex hormonal stimulation. In conclusion, the authors provide a possible explanation for the observed differences in expression in relation to the cause of death

A história da derivada de Mariana: uma experiência didática

Neste artigo introduzimos o conceito de derivada como quociente de infinitésimos através de uma história para crianças e adultos. Incluímos o relato da compreensão, da história e do conceito, demonstradas por duas meninas, uma de 10, outra de 12 anos. Segue uma breve apologia em favor do uso dos infinitésimos no ensino de cálculo e com a descrição do contexto de uma sala de aula de cálculo para calouros, onde essa história foi aplicada como ficha de trabalho. Lançamos um repto aos professor de cálculo e autores de livros textos: produzam algo igualmente acessível para apresentar o conceito de derivada pela via dos limites

Using Water Chemistry, Isotopes and Microbiology to Evaluate Groundwater Sources, Flow Paths and Geochemical Reactions in the Death Valley Flow System, USA

AbstractSprings of Ash Meadows and Furnace Creek (near or in Death Valley, CA) have nearly constant flow, temperature, chemistry, and similar δ2H and δ18O signatures. These factors indicate shared water sources and/or analogous geochemical reactions along similar flow paths. DNA-based (16S rRNA gene) microbial diversity assessments further illuminate these relationships. Whereas, all Ash Meadows springs share related archaeal populations, variations in carbon-14 (Crystal Spring) and strontium isotopes, Na+, SO2-, and methane concentrations (Big Spring), correspond with microbial differences within and between the two discharge areas. Similar geochemical signatures linking Ash Meadows and Furnace Creek springs appear to support a distinct end member at Big Spring in Ash Meadows, which is also supported by coincident enrichment in microbial methanogens and methanotrophs. Conversely, DNA libraries from a deep carbonate well (878 m) located between Ash Meadows and Furnace Creek (BLM-1), indicate no shared microbial diversity between Ash Meadows or Furnace Creek springs

Caspase 9 and caspase 3 immunohistochemical pattern in skeletal and cardiac muscles at different times after death: An experimental study on pmi estimation

(1) Background: The estimation of the post mortem interval (PMI) is a challenge for forensic pathologists because data emerging from methods commonly applied are not always conclusive, since several conditions exist that may affect the reliability of these parameters. Thus, new approaches have been proposed to overcome such a limit. In recent years, several studies have been performed on proteins analyzing their expression/degradation patterns in relation to the progressing of the post mortem interval. (2) Methods: The immunoreactivity patterns of two apoptosis mediators— Caspase 9 and Caspase 3—have been tested in order to evaluate their potential role as markers of the post mortem interval. The immunohistochemical analysis was performed on samples of skeletal and cardiac muscles obtained from rats at 0, 4, 8, 12, 24 and 72 h after death. (3) Results: The observed immunoreactivity patterns of both Caspase 9 and Caspase 3 showed a significant correlation with increasing post mortem interval either in skeletal or cardiac muscles, while the comparison of the immunoreactivity patterns of the two apoptotic mediators within each tissue appeared consistent with a preliminary activation of the “initiator” Caspase 9, which, in turn, subsequently activates the “executioner” Caspase 3. (4) Conclusion: The different expressions and decrease immunohistochemically observed on both caspases with progressing PMI support the usefulness of the combined analysis for post mortem interval estimation

Retinoblastoma Is Characterized by a Cold, CD8+ Cell Poor, PD-L1- Microenvironment, Which Turns Into Hot, CD8+ Cell Rich, PD-L1+ After Chemotherapy

PURPOSE. To investigate the impact of chemotherapy (CHT) on human retinoblastoma (RB) tumor microenvironment (TME).CASES AND METHODS. Ninety-four RBs were studied, including 44 primary RBs treated by upfront surgery (Group 1) and 50 primary RBs enucleated after CHT (CHT), either intraarterial (IAC; Group 2, 33 cases) or systemic (S-CHT; Group 3, 17 cases). Conventional and multiplexed immunohistochemistry were performed to make quantitative comparisons among the three groups, for the following parameters: tumor-infiltrating inflammatory cells (TI-ICs); programmed cell death protein 1 (PD-1) positive TI-ICs; Ki67 proliferation index; gliosis; PD-1 ligand (PD-L1) protein expression; vessel number. We also correlated these TME factors with the presence of histological high-risk factors (HHRF+) and RB anaplasia grade (AG).RESULTS. After CHT, a decrease in both RB burden and Ki67 positivity was observed. In parallel, most subsets of TI-ICs, PD-1+ TI-ICs, gliosis, and PD-L1 protein expression significantly increased (P < 0.001, P = 0.02, P < 0.001, respectively). Vessel number did not significantly vary. Age, HHRFs+ and AG were significantly different between primary and chemoreduced RBs (P < 0.001, P = 0.006, P = 0.001, respectively) and were correlated with most TME factors.CONCLUSIONS. CHT modulates host antitumor immunity by reorienting the RB TME from anergic into an active, CD8+, PD-L1+ hot state. Furthermore, some clinicopathological characteristics of RB correlate with several factors of TME. Our study adds data in favor of the possibility of a new therapeutic scenario in human RB

Understanding the Dermoscopic Patterns of Basal Cell Carcinoma Using Line-Field Confocal Tomography

: Basal cell carcinoma (BCC) is the most frequent malignancy in the general population. To date, dermoscopy is considered a key tool for the diagnosis of BCC; nevertheless, line-field confocal optical coherence tomography (LC-OCT), a new non-invasive optical technique, has become increasingly important in clinical practice, allowing for in vivo imaging at cellular resolution. The present study aimed to investigate the possible correlation between the dermoscopic features of BCC and their LC-OCT counterparts. In total, 100 histopathologically confirmed BCC cases were collected at the Dermatologic Clinic of the University of Siena, Italy. Predefined dermoscopic and LC-OCT criteria were retrospectively evaluated, and their frequencies were calculated. The mean (SD) age of our cohort was 65.46 (13.36) years. Overall, BCC lesions were mainly located on the head (49%), and they were predominantly dermoscopically pigmented (59%). Interestingly, all dermoscopic features considered had a statistically significant agreement with the LC-OCT criteria (all p < 0.05). In conclusion, our results showed that dermoscopic patterns may be associated with LC-OCT findings, potentially increasing accuracy in BCC diagnosis. However, further studies are needed in this field

Cognition and functioning in bipolar depression

Objectives: Depressive symptoms are associated with worse outcomes in patients with bipolar disorder (BD). However, scarce data are available regarding neurocognitive profiles across different areas of functioning among BD patients with moderate and severe depression. Our objective was to assess cognition and global functioning in a group of patients with bipolar depression. Methods: Data were available for 100 patients with bipolar depression (78% female) and 70 controls (64% female) paired by age and education level. Cognitive function was assessed with a neuropsychological test battery. Functioning was assessed with the Functioning Assessment Short Test. Results: In patients, severe depression was associated with poorer cognitive performance on measures of executive function. Patients with severe depression showed worse global functioning than those with moderate depression (z = 2.54, p = 0.011). In patients with severe depression, lower global functioning was associated with lower scores in working memory (r = -0.200, p = 0.010), and executive function (r = -0.210, p = 0.007; and r = 0.293, p o 0.001). Conclusion: Our findings suggest cognitive impairment and global functioning impairment are associated with the severity of depressive symptoms in bipolar depression. Intensive treatment of depressive symptoms in patients with BD is crucial to improve cognitive functioning and, consequently, functional outcomes

Contextualising the pervasive impact of macroeconomic austerity on prison health in England: A qualitative study among international policymakers

Background: Prisons offer the state the opportunity to gain access to a population that is at particularly high risk of ill-health. Despite the supportive legal and policy structures surrounding prison rehabilitation, the oppressive nature of the austerity policy in England threatens its advanced improvement.Methods: Using grounded theory methodology, this is the first interdisciplinary qualitative study to explore the impact of macroeconomic austerity on prison health in England from the perspective of 29 international prison policymakers.Results: The far-reaching impact of austerity in England has established a regressive political system that shapes the societal attitude towards social issues, which has exacerbated the existing poor health of the prisoners. Austerity has undermined the notion of social collectivism, imposed a culture of acceptance among prison bureaucrats and the wider community, and normalised the devastating impacts of prison instability. These developments are evidenced by the increasing levels of suicide, violence, radicalisation and prison gangs among prisoners, as well as the imposition of long working hours and the high levels of absenteeism among prison staff.Conclusions: This study underscores an important and yet unarticulated phenomenon that despite being the fifth largest economy in the world, England’s poorest, marginalised and excluded population continues to bear the brunt of austerity. Reducing the prison population, using international obligations as minimum standards to protect prisoners’ right to health and providing greater resources would create a more positive and inclusive system, in line with England’s international and domestic commitments to the humane treatment of all people

At the intersection between the subject and the political: a contribution to an ongoing discussion

The issue of subjectivity has recently occasioned a lively discussion in this journal opposing socioculturalism and Lacanian psychoanalysis. By confronting Luis Radford’s cultural theory with Jacques Lacan’s psychoanalysis, Tony Brown sought to show the limitations of socioculturalism. This article takes advantage of that discussion to develop a critique of Radford’s theory of objectification, taken as an exemplary sociocultural theorization of the teaching and learning of mathematics. It does so by extending the criticism made by Brown at the level of the subject, namely by showing what is lost in socioculturalism when it reduces the Hegelian notion of dialectics to a relation between constituted entities; but mostly by exploring the possibility opened by contemporary theory to posit the discussion around subjectivity in the political. While socioculturalism assumes the possibility of a synthesis between person and culture thus making education possible, it will be argued that a theory which assumes the impossibility of education is in a better position to, on the one hand, conceptualize the resistance of many towards the learning of mathematics, and on the other hand, to address the ongoing political failure in achieving the desired goal of “mathematics for all”