When Nice Guys Finish First: The Evolution of Cooperation, The Study of Law, and the Ordering of Legal Regimes

This Note adds to the scholarship in the area of Evolutionary Analysis and the Law (EA). EA is a paradigm that comments on the implications of evolution on the law. EA recognizes that many complex human behaviors that the law seeks to regulate have evolutionary origins that remain relevant today. This Note details how an understanding of the evolutionary basis of cooperation can bring about favorable revisions and reforms in the law. Following a review of the scientific foundation of EA, this Note sets forth the proposition that humans have an evolutionarily developed tendency to cooperate, an idea that contrasts the widely held belief that the evolutionary man is purely self-interested. This Note does, however, observe that the tendency to cooperate is not expressed at all times. This Note then explores the implications of EA on other areas of legal scholarship, such as behavioral law and economics, default rules in partnership law, and efficient mechanisms of trade. This Note concludes by addressing the concerns of EA critics and mapping a path for the future of EA

LIM and SH3 Protein -1 Modulates CXCR2-Mediated Cell Migration

BACKGROUND: The chemokine receptor CXCR2 plays a pivotal role in migration of neutrophils, macrophages and endothelial cells, modulating several biological responses such as angiogenesis, wound healing and acute inflammation. CXCR2 is also involved in pathogenesis of chronic inflammation, sepsis and atherosclerosis. The ability of CXCR2 to associate with a variety of proteins dynamically is responsible for its effects on directed cell migration or chemotaxis. The dynamic network of such CXCR2 binding proteins is termed as "CXCR2 chemosynapse". Proteomic analysis of proteins that co-immunoprecipitated with CXCR2 in neutrophil-like dHL-60 cells revealed a novel protein, LIM and SH3 protein 1 (LASP-1), binds CXCR2 under both basal and ligand activated conditions. LASP-1 is an actin binding cytoskeletal protein, involved in the cell migration. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that CXCR2 and LASP-1 co-immunoprecipitate and co-localize at the leading edge of migrating cells. The LIM domain of LASP-1 directly binds to the carboxy-terminal domain (CTD) of CXCR2. Moreover, LASP-1 also directly binds the CTD of CXCR1, CXCR3 and CXCR4. Using a site-directed and deletion mutagenesis approach, Iso323-Leu324 of the conserved LKIL motif on CXCR2-CTD was identified as the binding site for LASP-1. Interruption of the interaction between CXCR2-CTD and LIM domain of LASP-1 by dominant negative and knock down approaches inhibited CXCR2-mediated chemotaxis. Analysis for the mechanism for inhibition of CXCR2-mediated chemotaxis indicated that LASP-1/CXCR2 interaction is essential for cell motility and focal adhesion turnover involving activation of Src, paxillin, PAK1, p130CAS and ERK1/2. CONCLUSIONS/SIGNIFICANCE: We demonstrate here for the first time that LASP-1 is a key component of the "CXCR2 chemosynapse" and LASP-1 interaction with CXCR2 is critical for CXCR2-mediated chemotaxis. Furthermore, LASP-1 also directly binds the CTD of CXCR1, CXCR3 and CXCR4, suggesting that LASP-1 is a general mediator of CXC chemokine mediated chemotaxis. Thus, LASP-1 may serve as a new link coordinating the flow of information between chemokine receptors and nascent focal adhesions, especially at the leading edge. Thus the association between the chemokine receptors and LASP-1 suggests to the presence of a CXC chemokine receptor-LASP-1 pro-migratory module in cells governing the cell migration

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm’s potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

When Nice Guys Finish First: The Evolution of Cooperation, The Study of Law, and the Ordering of Legal Regimes

This Note adds to the scholarship in the area of Evolutionary Analysis and the Law (EA). EA is a paradigm that comments on the implications of evolution on the law. EA recognizes that many complex human behaviors that the law seeks to regulate have evolutionary origins that remain relevant today. This Note details how an understanding of the evolutionary basis of cooperation can bring about favorable revisions and reforms in the law. Following a review of the scientific foundation of EA, this Note sets forth the proposition that humans have an evolutionarily developed tendency to cooperate, an idea that contrasts the widely held belief that the evolutionary man is purely self-interested. This Note does, however, observe that the tendency to cooperate is not expressed at all times. This Note then explores the implications of EA on other areas of legal scholarship, such as behavioral law and economics, default rules in partnership law, and efficient mechanisms of trade. This Note concludes by addressing the concerns of EA critics and mapping a path for the future of EA

Theorizing Behavioral Law and Economics: A Defense of Evolutionary Analysis and the Law

Behavioral law and economics (BLE) provides a steady stream of empirical evidence that counters the predictions of law and economics. Despite this research and data, however, many theorists argue that BLE ultimately fails because it posits no underlying theory. This Note argues that perspectives from evolutionary biology, evolutionary psychology, and the brain sciences can provide the missing motivational theory for BLE\u27s empirical findings. The Note also examines the implications a more consistent and reasoned consideration of evolutionary analysis and the law (EA) has for our legal regime. In theorizing BLE and defending EA, this Note aims to show how evolutionary analysis can supplant law and economics in those instances where the latter\u27s predictions prove false and its incentive structure fails to motivate behavior

A Systematic Review and Evidence-based Analysis of Ingredients in Popular Male Fertility Supplements

To study the level of evidence available for ingredients of popular over-the-counter male fertility supplements. The top 17 male fertility supplements in the United States were identified from the most popular online retailers: A1 Supplements, Amazon, Vitamin Shoppe, and Walmart. Individual ingredients were identified for each supplement. The PUBMED and Cochrane online databases were reviewed for randomized controlled trials studying the efficacy of each ingredient. Each ingredient was categorized based on availability of evidence using an adapted version of the scoring system by the American Heart Association. Scores were assigned to each categorical level of evidence for each ingredient and a composite score for each supplement was calculated. Ninety unique ingredients were identified. The 5 most commonly used ingredients were vitamin E, folic acid, zinc, vitamin C, and selenium whereas the 5 ingredients with most evidence were L-carnitine, Vitamin E, Vitamin C, CoQ10, and Zinc. In all, only 22% of ingredients used were found to have published evidence for improvement in semen parameters and only 17% of ingredients had data published showing a positive effect. Our evidence-based analysis demonstrated an average composite rating of 1.66 (on a scale to 5). Evolution 60 and Conception XR had the highest composite scores with 3.6 and 3.5, respectively. Many male fertility supplements claim to improve fertility; however, their products are rarely backed by evidence and their efficacy remains unproven. Few ingredients used in popular fertility supplements have positive evidence in randomized clinical trials and should therefore be used cautiously