Improving cervical cancer screening, follow-up, and outcomes in incarcerated women

In the nation with the highest incarceration rate in the world, young women are currently the fastest-growing population with criminal legal system involvement in the United States. Incarcerated persons face extreme systemic vulnerabilities and are often victim to numerous injustices compared to the general population. Those in the criminal legal system also face an increased burden of chronic and communicable diseases, complicated by decreased access to medical care and increased risk factors that compound incidence of preventable diseases. Of these trends, the higher rates of cervical dysplasia and cervical cancer in female-bodied persons involved in the US incarceration system is especially troublesome considering the advancements in screening and prevention in the past twenty years. The increased incidence of cervical dysplasia and cervical cancer is a multifactorial issue that includes shared risk factors for disease development, barriers to healthcare access and affordability, lower health literacy scores and poor follow-up rates on abnormal results. With the increased burden of disease with worse morbidity and mortality, efforts are needed to improve the poor outcomes of cervical cancer in the populations of incarcerated women who are most affected by this preventable disease. Since the accessibility of the HPV vaccine and availability of regular screening modalities for cervical dysplasia, the rates of cervical cancer have decreased significantly in the first world. In order to address the World Health Organization’s goal to eliminate cervical cancer by 2030, the United States must focus on its populations most at risk of poor outcomes of this disease

An Effective Membrane Model of the Immunological Synapse

The immunological synapse is a patterned collection of different types of receptors and ligands that forms in the intercellular junction between T Cells and antigen presenting cells (APCs) during recognition. The synapse is implicated in information transfer between cells, and is characterized by different spatial patterns of receptors at different stages in the life cycle of T cells. We obtain a minimalist model that captures this experimentally observed phenomenology. A functional RG analysis provides further insights.Comment: 6 pages, 3 figures, submitted for publicatio

O Panorama Hermenêutico do Ordenamento Jurídico Pátrio e o Compliance Judicial dos Tribunais Superiores: Pesquisa Amostral sobre o Neoconstitucionalismo

This paper, guided by the deductive method, aims to analyze the observance of judicial action of brasilian law and is structured in three stages: (a) statement of the legal aspects regulate the exegesis of brazilian law; (b) the presentation of Neoconstitutionalism, as an interpretation of reference linked to the idea of justice;(c) study of three judged paradigms decided by the judicial courts. In this perspective, it questions whether the fundaments of the decisions to observe the laws of interpreting and applying the law, and if perquire about linking with Neoconstitutionalism.Este trabalho, guiado pelo método dedutivo, objetiva analisar a observância da atuação judicial das bases interpretativas dispostas ordenamento jurídico brasileiro e está estruturado em três etapas: (a) exposição dos aspectos jurídicos que disciplinam a exegese das normas jurídicas brasileiras; (b) a apresentação da Teoria Hermenêutica Neoconstitucionalista, como uma referência de interpretação vinculada à ideia de justiça; (c) estudo sobre três julgados paradigmas proferidos pelos tribunais superiores. Assim, observa-se se as fundamentações das decisões coadunam-se com as disposições legais sobre interpretação e aplicação da lei, verificando-se o Compliance Judicial, bem como se perquire sobre a vinculação com o Neoconstitucionalismo

Direitos Humanos e Movimentos Sociais como Manifestação para a Transformação do Estado Brasileiro

The articles are human rights and social movements, and aims to verify whether they are the way for the transformation of the Brazilian state. The theoretical framework adopted were the study Maria da Glória Gohn and the methodology chosen was the inductive - bibliographic / documentary. So reflect on the theme calls for a critical theoretical reasoning to identify the Brazilian unit from its multiplicity of content, culture, religion, principle. Thus, it is considered that the unified / tuned Civil society is the way to build another social structure - more just, egalitarian, democratic, ethical.O tema do artigo são os direitos humanos e os movimentos sociais, sendo que objetiva verificar se são o caminho para a transformação do Estado brasileiro. O marco teórico adotado foram os estudos de Maria da Glória Gohn e a metodologia escolhida foi a indutiva - bibliográfica/documental. Assim, refletir sobre o tema pede uma fundamentação teórica crítica, que identifique a unidade brasileira a partir da sua multiplicidade de conteúdo, cultura,  religiosidade,  princípio.  Dessa  forma,  considera-se  que  a  atuação  unificada/sintonizada da sociedade civil é o caminho para a construção de outra estrutura social – mais justa, igualitária, democrática, ética

Caveolin-1 expression in benign and malignant lesions of the breast

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

T-Cell activation: a queuing theory analysis at low agonist density

We analyze a simple linear triggering model of the T-cell receptor (TCR) within the framework of queuing theory, in which TCRs enter the queue upon full activation and exit by downregulation. We fit our model to four experimentally characterized threshold activation criteria and analyze their specificity and sensitivity: the initial calcium spike, cytotoxicity, immunological synapse formation, and cytokine secretion. Specificity characteristics improve as the time window for detection increases, saturating for time periods on the timescale of downregulation; thus, the calcium spike (30 s) has low specificity but a sensitivity to single-peptide MHC ligands, while the cytokine threshold (1 h) can distinguish ligands with a 30% variation in the complex lifetime. However, a robustness analysis shows that these properties are degraded when the queue parameters are subject to variation—for example, under stochasticity in the ligand number in the cell-cell interface and population variation in the cellular threshold. A time integration of the queue over a period of hours is shown to be able to control parameter noise efficiently for realistic parameter values when integrated over sufficiently long time periods (hours), the discrimination characteristics being determined by the TCR signal cascade kinetics (a kinetic proofreading scheme). Therefore, through a combination of thresholds and signal integration, a T cell can be responsive to low ligand density and specific to agonist quality. We suggest that multiple threshold mechanisms are employed to establish the conditions for efficient signal integration, i.e., coordinate the formation of a stable contact interface

T-Cell Artificial Focal Triggering Tools: Linking Surface Interactions with Cell Response

T-cell activation is a key event in the immune system, involving the interaction of several receptor ligand pairs in a complex intercellular contact that forms between T-cell and antigen-presenting cells. Molecular components implicated in contact formation have been identified, but the mechanism of activation and the link between molecular interactions and cell response remain poorly understood due to the complexity and dynamics exhibited by whole cell-cell conjugates. Here we demonstrate that simplified model colloids grafted so as to target appropriate cell receptors can be efficiently used to explore the relationship of receptor engagement to the T-cell response. Using immortalized Jurkat T cells, we monitored both binding and activation events, as seen by changes in the intracellular calcium concentration. Our experimental strategy used flow cytometry analysis to follow the short time scale cell response in populations of thousands of cells. We targeted both T-cell receptor CD3 (TCR/CD3) and leukocyte-function-associated antigen (LFA-1) alone or in combination. We showed that specific engagement of TCR/CD3 with a single particle induced a transient calcium signal, confirming previous results and validating our approach. By decreasing anti-CD3 particle density, we showed that contact nucleation was the most crucial and determining step in the cell-particle interaction under dynamic conditions, due to shear stress produced by hydrodynamic flow. Introduction of LFA-1 adhesion molecule ligands at the surface of the particle overcame this limitation and elucidated the low TCR/CD3 ligand density regime. Despite their simplicity, model colloids induced relevant biological responses which consistently echoed whole cell behavior. We thus concluded that this biophysical approach provides useful tools for investigating initial events in T-cell activation, and should enable the design of intelligent artificial systems for adoptive immunotherapy

Antigen-Engaged B Cells Undergo Chemotaxis toward the T Zone and Form Motile Conjugates with Helper T Cells

Interactions between B and T cells are essential for most antibody responses, but the dynamics of these interactions are poorly understood. By two-photon microscopy of intact lymph nodes, we show that upon exposure to antigen, B cells migrate with directional preference toward the B-zone–T-zone boundary in a CCR7-dependent manner, through a region that exhibits a CCR7-ligand gradient. Initially the B cells show reduced motility, but after 1 d, motility is increased to approximately 9 μm/min. Antigen-engaged B cells pair with antigen-specific helper T cells for 10 to more than 60 min, whereas non-antigen-specific interactions last less than 10 min. B cell–T cell conjugates are highly dynamic and migrate extensively, being led by B cells. B cells occasionally contact more than one T cell, whereas T cells are strictly monogamous in their interactions. These findings provide evidence of lymphocyte chemotaxis in vivo, and they begin to define the spatiotemporal cellular dynamics associated with T cell–dependent antibody responses

Elevation of circulating big endothelin-1: an independent prognostic factor for tumor recurrence and survival in patients with esophageal squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Endothelin(ET) axis plays a key role in many tumor progression and metastasis via various mechanisms such as angiogenesis, mediating extracellular matrix degradation and inhibition of apoptosis. However, there is limited information regarding the clinical significance of plasma big ET-1 levels in esophageal cancer patients. Circulating plasma big ET-1 levels were measured in patients with esophageal squamous cell carcinoma(ESCC) to evaluate the value of ET-1 as a biomarker for predicting tumor recurrence and patients survival.</p> <p>Methods</p> <p>Preoperative plasma big ET-1 concentrations were measured by an enzyme linked immunosorbent assay(ELISA) in 108 ESCC patients before surgery, and then again at 1,2,3,10 and 30 days after curative radical resection for ESCC. The association between preoperative plasma big ET-1 levels and clinicopathological features, tumor recurrence and patient survival, and their changes following surgery were evaluated.</p> <p>Results</p> <p>The preoperative plasma big ET-1 levels in ESCC patients were significantly higher than those in controls. And there was a significant association between plasma big ET-1 levels and disease stage, as well as invasion depth of the tumor and lymph node status. Furthermore, plasma big ET-1 levels decreased significantly after radical resection of the primary tumor and patients with postoperative recurrence had significantly higher plasma big ET-1 levels than that of patients without recurrence. Finally, the survival rate of patients with higher plasma big ET-1 concentrations (>4.3 pg/ml) was significantly lower than that of patients with lower level (≤ 4.3 pg/ml). Multivariate regression analysis showed that plasma big ET-1 level is an independent prognostic factor for survival in patients with ESCC.</p> <p>Conclusion</p> <p>Plasma big ET-1 level in ESCC patients may reflect malignancy and predict tumor recurrence and patient survival. Therefore, the preoperative plasma big ET-1 levels may be a clinically useful biomarker for choice of multimodality therapy in ESCC patients.</p