The Effects of Middle Cerebral Artery Occlusion on Central Nervous System Apoptotic Events in Normal and Diabetic Rats

Apoptosis and neural degeneration are characteristics of cerebral ischemia and brain damage. Diabetes is associated with worsening of brain damage following ischemic events. In this study, the authors characterize the influence of focal cerebral ischemia, induced by middle cerebral artery occlusion, on 2 indexes of apoptosis,TUNEL(terminal deoxynucleotidyl transferase–mediated deoxyuridine 5-triphosphate nick end-labeling) staining and caspase- 3 immunohistochemistry. Diabetes was induced in normal rats using streptozotocin and maintained for 5 to 6 weeks. The middle cerebral artery of both normal and diabetic rats was occluded and maintained from 24 or 48 hours. Sham-operated normal and diabetic animals served as controls. Following 24 to 48 hours of occlusion, the animals were sacrificed and the brains were removed, sectioned, and processed for TUNEL staining or caspase-3 immunohistochemistry. Middle cerebral artery occlusion in normal rats was associated with an increase in the number of both TUNEL-positive and caspase-3– positive cells in selected brain regions (hypothalamic preoptic area, piriform cortex, and parietal cortex) when compared to nonoccluded controls. Diabetic rats without occlusion showed significant increases in both TUNEL-positive and caspase-3–positive cells compared to normal controls. Middle cerebral artery occlusion in diabetic rats resulted in increases in TUNEL-positive as well as caspase-3–positive cells in selected regions, above those seen in nonoccluded diabetic rats. Both TUNEL staining and caspase-3 immunohistochemistry revealed that the number of apoptotic cells in diabetic animals tended to be greatest in the preoptic area and parietal cortex. The authors conclude that focal cerebral ischemia is associated with a significant increase in apoptosis in nondiabetic rats, and that diabetes alone or diabetes plus focal ischemia are associated with significant increases in apoptotic cells

The Effect of the Removal of the Area Postrema on Insulin and IGF-1-Induced Cardiovascular and Sympathetic Nervous Responses

Previous studies have demonstrated that insulin and IGF-1 both increase lumbar sympathetic nerve activity (LSNA) and decrease mean arterial pressure (MAP). We hypothesized that the peripheral responses to insulin and IGF-1 are mediated, at least in part, via the central nervous system. In this study we determined the effects of the peripheral administration of both insulin and IGF-1 on cardiovascular dynamics and LSNA following removal of the area postrema (APX), a major site of blood-brain communication. Insulin infusion in normal rats decreased MAP but increased HR and LSNA. When insulin was infused in APX rats it also decreased the MAP but the MAP recovered rapidly and plateaued at a level equivalent to normals after 40 min. Insulin significantly increased the HR and LSNA in the APX rats compared to normals. However, when hypoglycemia was prevented by glucose infusion, the HR and LSNA responses to insulin in the APX rats were similar to normals. IGF-1 also decreased MAP and to a greater extent in the APX rats compared to normals but the increased LSNA in APX rats was equivalent to normals. The APX rats when compared to normals had a greater sensitivity to insulin-induced hypoglycemia while IGF-1 decreased the plasma glucose to a lesser degree in APX rats. We conclude that insulin and IGF-1 entry into the CNS at least via the area postrema does not contribute significantly to the hypotensive response and that the greater depressor response to IGF-1 is likely due to enhanced vascular sensitivity in APX rats. The increased HR and LSNA following insulin were likely mediated by an increased reflexive response to hypoglycemia

Using GIS technology to identify areas of tuberculosis transmission and incidence

BACKGROUND: Currently in the U.S. it is recommended that tuberculosis screening and treatment programs be targeted at high-risk populations. While a strategy of targeted testing and treatment of persons most likely to develop tuberculosis is attractive, it is uncertain how best to accomplish this goal. In this study we seek to identify geographical areas where on-going tuberculosis transmission is occurring by linking Geographic Information Systems (GIS) technology with molecular surveillance. METHODS: This cross-sectional analysis was performed on data collected on persons newly diagnosed with culture positive tuberculosis at the Tarrant County Health Department (TCHD) between January 1, 1993 and December 31, 2000. Clinical isolates were molecularly characterized using IS6110-based RFLP analysis and spoligotyping methods to identify patients infected with the same strain. Residential addresses at the time of diagnosis of tuberculosis were geocoded and mapped according to strain characterization. Generalized estimating equations (GEE) analysis models were used to identify risk factors involved in clustering. RESULTS: Evaluation of the spatial distribution of cases within zip-code boundaries identified distinct areas of geographical distribution of same strain disease. We identified these geographical areas as having increased likelihood of on-going transmission. Based on this evidence we plan to perform geographically based screening and treatment programs. CONCLUSION: Using GIS analysis combined with molecular epidemiological surveillance may be an effective method for identifying instances of local transmission. These methods can be used to enhance targeted screening and control efforts, with the goal of interruption of disease transmission and ultimately incidence reduction

Incipient Cognition Solves the Spatial Reciprocity Conundrum of Cooperation

Background: From the simplest living organisms to human societies, cooperation among individuals emerges as a paradox difficult to explain and describe mathematically, although very often observed in reality. Evolutionary game theory offers an excellent toolbar to investigate this issue. Spatial structure has been one of the first mechanisms promoting cooperation; however, alone it only opens a narrow window of viability. Methodology/Principal Findings: Here we equip individuals with incipient cognitive abilities, and investigate the evolution of cooperation in a spatial world where retaliation, forgiveness, treason and mutualism may coexist, as individuals engage in Prisoner’s Dilemma games. In the model, individuals are able to distinguish their partners and act towards them based on previous interactions. We show how the simplest level of cognition, alone, can lead to the emergence of cooperation. Conclusions/Significance: Despite the incipient nature of the individuals ’ cognitive abilities, cooperation emerges for unprecedented values of the temptation to cheat, being also robust to invasion by cheaters, errors in decision making an

Volume 09

Introduction Dr. Roger A. Byrne Islamic Radicalization of Women in The United Kingdom by Mackenzie Adamson Harmony by Chad Benton The Rhetoric of Distrust: A Dangerous Game During the 2016 Presidential Campaign by Garrett Badgley Neither Man nor Monster: Frankenstein\u27s Creature as Posthuman by Anna Bultrowicz Holisticrx by Kelsey Daniel Reality Bytes: Identity in the Virtual World of Ernest Cline\u27s Ready Player One by Taylor Embrey Animation by Jose Romero Sue Klebold\u27s a Mother\u27s Reckoning: A Call to Action for Mental Health Advocacy by Taylor Hughes Hillary Clinton\u27s Rhetoric of Gender Inequality: The Past, the Present, nd the (Hypothetical) Future by Haley Klepatzki Against the Grain: Eat Gluten Free by Emily Spittle Following Judith: A Midrashic Approach to the Book of Judith by Kelsey Longnaker Identity and Dialect Adaptation: The Effect of Geography and Community on Dialect by Alexis Paige Manuel These are the Gardens Of The Desert : The Revolutionary Impact Of Bryant\u27s The Prairies on American Literature by Montana Nelson Beauty is Pain: Eating Disorders, Gender, and the Lies We Feed Young Women By Faith Shelton Be a Man: The Eradication of Gender in Y: The Last Man by Joseph Stearman A Computational Study of Molecular Electronics: The Role of Molecular Structure by John Brumfield The Importance of Voting by Monica Mcgraw Method for The Detection and Removal of Antibiotics in Bottled Water by Jayden Metzger Small Chimp Print by Maddie Smith Mental Health Impairments in Rural Communities by Lyndsey Swinhart F@#* That: The Effects of Swearing and Influence of Authority on Stress Level by Amanda N. Chappell And Haley C. Moore Friend or Faux? Prosocial and Antisocial Social Media Use and Personality Traits by Samantha Burgess, Heather Dunbar, Briana Hackett, Jackie Mcmillion, Kiana Simpkins, And Ta\u27miya Vanhook-Davis There\u27s Someone in My Head but It’s Not Me : Attitudes About Diagnosis and Treatment of Psychological Disorders by Kiana Simpkins, Lindsey Sparrock, And Leonie Verstraete Efflorescent Bonds by Kristen Melton Shower Thoughts by Ryan Bultrowic

Lessons Learned Developing a Diagnostic Tool for HIV-Associated Dementia Feasible to Implement in Resource-Limited Settings: Pilot Testing in Kenya

Objective: To conduct a preliminary evaluation of the utility and reliability of a diagnostic tool for HIV-associated dementia (HAD) for use by primary health care workers (HCW) which would be feasible to implement in resource-limited settings. Background: In resource-limited settings, HAD is an indication for anti-retroviral therapy regardless of CD4 T-cell count. Anti-retroviral therapy, the treatment for HAD, is now increasingly available in resource-limited settings. Nonetheless, HAD remains under-diagnosed likely because of limited clinical expertise and availability of diagnostic tests. Thus, a simple diagnostic tool which is practical to implement in resource-limited settings is an urgent need. Methods: A convenience sample of 30 HIV-infected outpatients was enrolled in Western Kenya. We assessed the sensitivity and specificity of a diagnostic tool for HAD as administered by a primary HCW. This was compared to an expert clinical assessment which included examination by a physician, neuropsychological testing, and in selected cases, brain imaging. Agreement between HCW and an expert examiner on certain tool components was measured using Kappa statistic. Results: The sample was 57 % male, mean age was 38.6 years, mean CD4 T-cell count was 323 cells/mL, and 54 % had less than a secondary school education. Six (20%) of the subjects were diagnosed with HAD by expert clinical assessment. The diagnostic tool was 63 % sensitive and 67 % specific for HAD. Agreement between HCW and expert examiners was poor for many individual items of the diagnostic tool (K =.03–.65). This diagnostic tool had moderate sensitivity and specificity fo

A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE).

BackgroundOfranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab.MethodsThis pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 1013 viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary endpoints were objective response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria and progression-free survival (PFS).ResultsEnrolled were 256 patients at 57 sites. Median exposure to VB-111 was 4 months. The study did not meet its primary or secondary goals. Median OS was 6.8 versus 7.9 months in the combination versus control arm (hazard ratio, 1.20; 95% CI: 0.91-1.59; P = 0.19) and ORR was 27.3% versus 21.9% (P = 0.26). A higher rate of grades 3-5 adverse events was reported in the combination arm (67% vs 40%), mainly attributed to a higher rate of CNS and flu-like/fever events. Trends for improved survival with combination treatment were seen in the subgroup of patients with smaller tumors and in patients who had a posttreatment febrile reaction.ConclusionsIn this study, upfront concomitant administration of VB-111 and bevacizumab failed to improve outcomes in rGBM. Change of treatment regimen, with the lack of VB-111 monotherapy priming, may explain the differences from the favorable phase II results.Clinical trials registrationNCT02511405

Empirical Legal Studies Before 1940: A Bibliographic Essay

The modern empirical legal studies movement has well-known antecedents in the law and society and law and economics traditions of the latter half of the 20th century. Less well known is the body of empirical research on legal phenomena from the period prior to World War II. This paper is an extensive bibliographic essay that surveys the English language empirical legal research from approximately 1940 and earlier. The essay is arranged around the themes in the research: criminal justice, civil justice (general studies of civil litigation, auto accident litigation and compensation, divorce, small claims, jurisdiction and procedure, civil juries), debt and bankruptcy, banking, appellate courts, legal needs, legal profession (including legal education), and judicial staffing and selection. Accompanying the essay is an extensive bibliography of research articles, books, and reports

A systematic review of risk factors for mortality among tuberculosis patients in South Africa

Background Tuberculosis (TB)-associated mortality in South Africa remains high. This review aimed to systematically assess risk factors associated with death during TB treatment in South African patients. Methods We conducted a systematic review of TB research articles published between 2010 and 2018. We searched BioMed Central (BMC), PubMed®, EBSCOhost, Cochrane, and SCOPUS for publications between January 2010 and December 2018. Searches were conducted between August 2019 and October 2019. We included randomised control trials (RCTs), case control, cross sectional, retrospective, and prospective cohort studies where TB mortality was a primary endpoint and effect measure estimates were provided for risk factors for TB mortality during TB treatment. Due to heterogeneity in effect measures and risk factors evaluated, a formal meta-analysis of risk factors for TB mortality was not appropriate. A random effects meta-analysis was used to estimate case fatality ratios (CFRs) for all studies and for specific subgroups so that these could be compared. Quality assessments were performed using the Newcastle-Ottawa scale or the Cochrane Risk of Bias Tool. Results We identified 1995 titles for screening, 24 publications met our inclusion criteria (one cross-sectional study, 2 RCTs, and 21 cohort studies). Twenty-two studies reported on adults (n = 12561) and two were restricted to children < 15 years of age (n = 696). The CFR estimated for all studies was 26.4% (CI 18.1–34.7, n = 13257 ); 37.5% (CI 24.8-50.3, n = 5149) for drug-resistant (DR) TB; 12.5% (CI 1.1–23.9, n = 1935) for drug-susceptible (DS) TB; 15.6% (CI 8.1–23.2, n = 6173) for studies in which drug susceptibility was mixed or not specified; 21.3% (CI 15.3-27.3, n = 7375) for people living with HIV/AIDS (PLHIV); 19.2% (CI 7.7–30.7, n = 1691) in HIV-negative TB patients; and 6.8% (CI 4.9–8.7, n = 696) in paediatric studies. The main risk factors associated with TB mortality were HIV infection, prior TB treatment, DR-TB, and lower body weight at TB diagnosis. Conclusions In South Africa, overall mortality during TB treatment remains high, people with DR-TB have an elevated risk of mortality during TB treatment and interventions to mitigate high mortality are needed. In addition, better prospective data on TB mortality are needed, especially amongst vulnerable sub-populations including young children, adolescents, pregnant women, and people with co-morbidities other than HIV. Limitations included a lack of prospective studies and RCTs and a high degree of heterogeneity in risk factors and comparator variables