Abraham Lincoln, Aortic Regurgitation and Abscesses

Abraham Lincoln was an exceptionally tall man with a long, thin face and huge hands and feet. His mother had a similar build – an observation that in 1962 led AM Gordon to first propose that President Lincoln had Marfan syndrome

Magnetically Actuated Protease Sensors for in Vivo Tumor Profiling

Targeted cancer therapies require a precise determination of the underlying biological processes driving tumorigenesis within the complex tumor microenvironment. Therefore, new diagnostic tools that capture the molecular activity at the disease site in vivo are needed to better understand tumor behavior and ultimately maximize therapeutic responses. Matrix metalloproteinases (MMPs) drive multiple aspects of tumorigenesis, and their activity can be monitored using engineered peptide substrates as protease-specific probes. To identify tumor specific activity profiles, local sampling of the tumor microenvironment is necessary, such as through remote control of probes, which are only activated at the tumor site. Alternating magnetic fields (AMFs) provide an attractive option to remotely apply local triggering signals because they penetrate deep into the body and are not likely to interfere with biological processes due to the weak magnetic properties of tissue. Here, we report the design and evaluation of a protease-activity nanosensor that can be remotely activated at the site of disease via an AMF at 515 kHz and 15 kA/m. Our nanosensor was composed of thermosensitive liposomes containing functionalized protease substrates that were unveiled at the target site by remotely triggered heat dissipation of coencapsulated magnetic nanoparticles (MNPs). This nanosensor was combined with a unique detection assay to quantify the amount of cleaved substrates in the urine. We applied this spatiotemporally controlled system to determine tumor protease activity in vivo and identified differences in substrate cleavage profiles between two mouse models of human colorectal cancer.National Cancer Institute (U.S.) (Grant P30-CA14051)National Institute of Environmental Health Sciences (Grant P30-ES002109)United States. Defense Advanced Research Projects Agency (Award HR0011-15-C-0155

Feminisms and decolonising psychology: Possibilities and challenges

In this special issue, we bring together papers that speak to feminisms in relation to decolonisation in the discipline of psychology. The six articles and two book reviews address a range of issues: race, citizenship, emancipatory politics, practising decolonial refusal, normalising slippery subjectivity, Islamic anti-patriarchal liberation psychology, and decolonisation of the hijab. In this editorial we outline the papers’ contributions to discussions on understanding decolonisation, how feminisms and decolonisation speak to each other, and the implications of the papers for feminist decolonising psychology. Together the papers highlight the importance of undermining the gendered coloniality of power, knowledge and being. The interweaving of feminisms and decolonising efforts can be achieved through: each mutually informing and shaping the other, conducting intersectional analyses, and drawing on transnational feminisms. Guiding principles for feminist decolonising psychology include: undermining the patriarchal colonialist legacy of mainstream psychological science; connecting gendered coloniality with other systems of power such as globalisation; investigating topics that surface the intertwining of colonialist and gendered power relations; using research methods that dovetail with feminist decolonising psychology; and focussing praxis on issues that enable decolonisation. Given the complexities of the coloniality and patriarchy of power-knowledge-being, feminist decolonising psychology may fail. The issues raised in this special issue point to why it mustn’t

Anti-Proliferative Role of Recombinant Lethal Toxin of Bacillus Anthracis on Primary Mammary Ductal Carcinoma Cells Revealing Its Therapeutic Potential

Bacillus anthracis secretes three secretary proteins; lethal factor (LF), protective antigen (PA) and edema factor (EF). The LF has ability to check proliferation of mammary tumors, chiefly depending on mitogen activated protein kinase (MAPK) signaling pathway. Evaluation of therapeutic potential of recombinant LF (rLF), recombinant PA (rPA) and lethal toxin (rLF + rPA = LeTx) on the primary mammary ductal carcinoma cells revealed significant (p \u3c 0.01) reduction in proliferation of tumor cells with mean inhibition indices of 28.0 ±1.37% and 19.6 ± 1.47% respectively. However, treatment with rPA alone had no significant anti-proliferative effect as evident by low mean inhibition index of 3.4 ± 3.87%. The higher inhibition index observed for rLF alone as compared to LeTx is contrary to the existing knowledge on LF, which explains the requirement of PA dependent endocytosis for its enzymatic activity. Therefore, the plausible existence of PA independent mode of action of LF including direct receptor mediated endocytosis or modulation of signal transduction cascade via unknown means is hypothesized. In silico protein docking analysis of other cellular receptors for any plausibility to play the role of receptor for LF revealed c-Met receptor showing strongest affinity for LF (H bond = 19; Free energy = -773.96), followed by nerve growth factor receptor (NGFR) and human epidermal growth factor receptor (HER)-1. The study summarizes the use of rLF or LeTx as therapeutic molecule against primary mammary ductal carcinoma cells and also the c-Met as potential alternative receptor for LF to mediate and modulate PA independent signal transduction

Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications.

PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence. METHODS: Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed. RESULTS: ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with 1-year rates of 74% versus 21% (adjusted HR, 7.4 [95% CI, 2.7 to 20]). CONCLUSION: ctDNA testing exhibited high prognostic accuracy in detecting MCC recurrence, suggesting its potential to reduce frequent surveillance imaging. ctDNA also identifies high-risk patients who need more frequent imaging and may be best suited for adjuvant therapy trials

Early Detection of Lung Nodules Using a Revolutionized Deep Learning Model

According to the WHO (World Health Organization), lung cancer is the leading cause of cancer deaths globally. In the future, more than 2.2 million people will be diagnosed with lung cancer worldwide, making up 11.4% of every primary cause of cancer. Furthermore, lung cancer is expected to be the biggest driver of cancer-related mortality worldwide in 2020, with an estimated 1.8 million fatalities. Statistics on lung cancer rates are not uniform among geographic areas, demographic subgroups, or age groups. The chance of an effective treatment outcome and the likelihood of patient survival can be greatly improved with the early identification of lung cancer. Lung cancer identification in medical pictures like CT scans and MRIs is an area where deep learning (DL) algorithms have shown a lot of potential. This study uses the Hybridized Faster R-CNN (HFRCNN) to identify lung cancer at an early stage. Among the numerous uses for which faster R-CNN has been put to good use is identifying critical entities in medical imagery, such as MRIs and CT scans. Many research investigations in recent years have examined the use of various techniques to detect lung nodules (possible indicators of lung cancer) in scanned images, which may help in the early identification of lung cancer. One such model is HFRCNN, a two-stage, region-based entity detector. It begins by generating a collection of proposed regions, which are subsequently classified and refined with the aid of a convolutional neural network (CNN). A distinct dataset is used in the model’s training process, producing valuable outcomes. More than a 97% detection accuracy was achieved with the suggested model, making it far more accurate than several previously announced methods

Socio-Economic Inequalities in the Use of Postnatal Care in India

OBJECTIVES: First, our objective was to estimate socio-economic inequalities in the use of postnatal care (PNC) compared with those in the use of care at birth and antenatal care. Second, we wanted to compare inequalities in the use of PNC between facility births and home births and to determine inequalities in the use of PNC among mothers with high-risk births. METHODS AND FINDINGS: Rich-poor ratios and concentration indices for maternity care were estimated using the third round of the District Level Household Survey conducted in India in 2007-08. Binary logistic regression models were used to examine the socio-economic inequalities associated with use of PNC after adjusting for relevant socio-economic and demographic characteristics. PNC for both mothers and newborns was substantially lower than the care received during pregnancy and child birth. Only 44% of mothers in India at the time of survey received any care within 48 hours after birth. Likewise, only 45% of newborns received check-up within 24 hours of birth. Mothers who had home births were significantly less likely to have received PNC than those who had facility births, with significant differences across the socio-economic strata. Moreover, the rich-poor gap in PNC use was significantly wider for mothers with birth complications. CONCLUSIONS: PNC use has been unacceptably low in India given the risks of mortality for mothers and babies shortly after birth. However, there is evidence to suggest that effective use of pregnancy and childbirth care in health facilities led to better PNC. There are also significant socio-economic inequalities in access to PNC even for those accessing facility-based care. The coverage of essential PNC is inadequate, especially for mothers from economically disadvantaged households. The findings suggest the need for strengthening PNC services to keep pace with advances in coverage for care at birth and prenatal services in India through targeted policy interventions

Therapeutic effects of pyrrolidine dithiocarbamate on acute lung injury in rabbits

<p>Abstract</p> <p>Background</p> <p>Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is an early characteristic of multiple organ dysfunction, responsible for high mortality and poor prognosis in patients. The present study aims to evaluate therapeutic effects and mechanisms of pyrrolidine dithiocarbamate (PDTC) on ALI.</p> <p>Methods</p> <p>Alveolar-arterial oxygen difference, lung tissue edema and compromise, NF-κB activation in polymorphonuclear neutrophil (PMN), and systemic levels of tumor necrosis factor-alpha (TNFa) and intercellular adhesion molecule-1 (ICAM-1) in rabbits induced by the intravenous administration of lipopolysaccharide (LPS) and treated with PDTC. Production of TNFa and IL-8, activation of Cathepsin G, and PMNs adhesion were also measured.</p> <p>Results</p> <p>The intravenous administration of PDTC had partial therapeutic effects on endotoxemia-induced lung tissue edema and damage, neutrophil influx to the lung, alveolar-capillary barrier dysfunction, and high systemic levels of TNFa and ICAM-1 as well as over-activation of NF-κB. PDTC could directly and partially inhibit LPS-induced TNFa hyper-production and over-activities of Cathepsin G. Such inhibitory effects of PDTC were related to the various stimuli and enhanced through combination with PI3K inhibitor.</p> <p>Conclusion</p> <p>NF-κB signal pathway could be one of targeting molecules and the combination with other signal pathway inhibitors may be an alternative of therapeutic strategies for ALI/ARDS.</p