Texas Southern University
Texas Southern University, School of Public Affairs: Digital ScholarshipNot a member yet
21372 research outputs found
Sort by
Interleukin-17-induced neutrophil extracellular traps mediate resistance to checkpoint blockade in pancreatic cancer
Get PDFPancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy with an immunosuppressive microenvironment that is resistant to most therapies. IL17 is involved in pancreatic tumorigenesis, but its role in invasive PDAC is undetermined. We hypothesized that IL17 triggers and sustains PDAC immunosuppression. We inhibited IL17/IL17RA signaling using pharmacological and genetic strategies alongside mass cytometry and multiplex immunofluorescence techniques. We uncovered that IL17 recruits neutrophils, triggers neutrophil extracellular traps (NETs), and excludes cytotoxic CD8 T cells from tumors. Additionally, IL17 blockade increases immune checkpoint blockade (PD-1, CTLA4) sensitivity. Inhibition of neutrophils or Padi4-dependent NETosis phenocopies IL17 neutralization. NMR spectroscopy revealed changes in tumor lactate as a potential early biomarker for IL17/PD-1 combination efficacy. Higher expression of IL17 and PADI4 in human PDAC corresponds with poorer prognosis, and the serum of patients with PDAC has higher potential for NETosis. Clinical studies with IL17 and checkpoint blockade represent a novel combinatorial therapy with potential efficacy for this lethal disease
In vitro and in vivo characterization of potent antileishmanial methionine aminopeptidase 1 inhibitors
Get PDFLeishmania major is the causative agent of cutaneous leishmaniasis (CL). No human vaccine is available for CL, and current drug regimens present several drawbacks, such as emerging resistance, severe toxicity, medium effectiveness, and/or high cost. Thus, the need for better treatment options against CL is a priority. In the present study, we validate the enzyme methionine aminopeptidase 1 of L. major (MetAP1Lm), a metalloprotease that catalyzes the removal of N-terminal methionine from peptides and proteins, as a chemotherapeutic target against CL infection. The in vitro antileishmanial activities of eight novel MetAP1 inhibitors (OJT001 to OJT008) were investigated. Three compounds, OJT006, OJT007, and OJT008, demonstrated potent antiproliferative effects in macrophages infected with L. major amastigotes and promastigotes at submicromolar concentrations, with no cytotoxicity against host cells. Importantly, the leishmanicidal effect in transgenic L. major promastigotes overexpressing MetAP1Lm was diminished by almost 10-fold in comparison to the effect in wild-type promastigotes. Furthermore, the in vivo activities of OJT006, OJT007, and OJT008 were investigated in L. major-infected BALB/c mice. In comparison to the footpad parasite load in the control group, OJT008 decreased the footpad parasite load significantly, by 86%, and exhibited no toxicity in treated mice. We propose MetAP1 inhibitor OJT008 as a potential chemotherapeutic candidate against CL infection caused by L. major infection
Spinal Cord Injury Provider Knowledge and Attitudes Toward Bacteriuria Management and Antibiotic Stewardship
No full textIntroduction: Bacteriuria, either asymptomatic or urinary tract infection, is common in persons with spinal cord injury or disorder (SCI/D). In the Veterans Health Administration (VHA), conflicting clinical practice guidelines make appropriate bacteriuria management and antibiotic stewardship challenging. Objective: To explore SCI/D provider knowledge, attitudes, and teamwork around bacteriuria management during the VHA SCI/D annual examination. Design: Mixed methods. Setting: VHA SCI/D centers. Participants: SCI/D staff providers and physical medicine and rehabilitation resident physicians. Main Outcome Measurements: Knowledge, safety, and teamwork scores on bacteriuria management using a validated questionnaire. Themes on barriers and facilitators to bacteriuria management during the SCI/D annual exam, and attitudes toward antibiotic stewardship in general. Results: We received 84 responses from 344 distributed surveys, with a response rate of 24%. Thirty percent of all participants endorsed incorrect triggers for obtaining a urine culture (change in urine color, cloudiness, or odor). The type of organism identified on culture drove unnecessary antibiotic use; 57% would treat asymptomatic bacteriuria if caused by extended spectrum beta-lactamase Escherichia coli. There were no significant differences between the median (interquartile range [IQR]) knowledge score of the staff providers (70.6 [58.8-82.4]) and the resident physicians (64.7 [58.8-82.4]), but the teamwork climate scores (P =.02) and safety climate scores (P \u3c.01) were higher among staff providers than among resident physicians. Interview analysis identified how the limited recall of content among SCI/D providers of the guidelines for bacteriuria was a potential barrier to their use but attitudes toward guidelines and antibiotic stewardship initiatives were positive. Conclusion: All participants objectively demonstrated actionable gaps in bacteriuria management and expressed uncertainty in their knowledge during qualitative interviews. Through addressing these gaps, we can develop effective antibiotic stewardship programs for the VHA SCI/D system of care
Statistical analysis of safety performance of displaced left-turn intersections: Case studies in San Marcos, Texas
Get PDFDisplaced left-turn (DLT) intersections are designed to increase the mobility of vehicles by relocating the left-turn lane (lanes) to the far-left side of the road upstream of the main signalized intersection. Since DLT is a relatively new design and very limited crash data are available, previous studies have focused mainly on the analysis of its operational performance rather than its safety performance. To fill this gap, in this study, we investigated the safety performance of two DLT intersections located in San Marcos, Texas. Crash data from 2011 to April 2018 were extracted from the TxDOT Crash Record Information System (CRIS). These crash data were analyzed using two different approaches, i.e., statistical analysis and collision diagram-based analysis. The results of this study indicated that DLT did not increase the overall crash frequencies at the studied intersections. Traffic crashes related to left turns and right turns were reduced significantly by DLT. Meanwhile, it also caused safety issues related to traffic signage, traffic signal, geometric design, and access management at DLT intersections. Thus, in the implementation of DLT intersections, traffic engineers need to carefully consider different aspects of the DLT intersection design, including access management, traffic signal coordination, and driver acceptance. As a result of these analyses, recommendations were provided for the safe implementation of the DLT design in the future
Review of the Latest Trends in Transplantation Immunology and its Role in Mortality Reduction
Get PDFTransplantation immunology deals with the process of moving cells, tissues, or organs, from one site to another, either within the same person or between a donor and a recipient. If an organ system fails, or becomes damaged because of disease or injury, it can be replaced with a healthy organ or tissue from a donor. The process of transplantation has become increasingly popular due to its life saving benefit. In 2015 /2016 4601 patients\u27 lives were saved or improved by an organ transplant in the United Kingdom alone. Kidney transplants are the most common organ transplant followed by liver and pancreas. However, the complexity of the immune system of humans makes the process challenging. None the less immunosuppressive regimen has been introduced to reduce rejection and life-threatening consequences associated with transplant rejection. Data support the increasing benefit of the transplantation in the reduction of mortality or individuals with life threatening conditions improving their quality of life considerably. This work aims at exploring the overall benefit of transplantation in health care especially as it pertains to the reduction of mortality rate for patients in the United States and around the world
Familism and Crime in Nigeria: Exploring Family Conduct and Implication on Expanding New Spaces of Crime in Akwa Ibom State
Get PDFThe study investigates the influence of the family on crime in Nigeria, and emphasizes how conformance/non-conformance to family values have induced an expansion on the spaces of crime. Focusing on the Ibibio people of South-South Nigeria, this qualitative survey study adopts the socio-stuctural explanation of crime. Relying on simple percentage for data analysis, emerging data reveal the notion that familism emphasizes loyalty, trust, integrity, unity, progress and defence of family values. It notes that the changing societal attitudes to family values have led to the emergence of new spaces of crime. The paper concludes that police deployment, the resort to self-help and enforcement of conformity reactionary to the emerging crime problem have induced the emergence of new frontiers of anti-social activities which are not explicitly mainstreamed within extant crime management realities. It recommends the imperativeness of proper evolution of the criminal justice system for coping with the emerging trend