Now showing items 41-60 of 12647

    • Mass Drug Administration of Azithromycin to Reduce Child Mortality: Only for High-Mortality Settings?

      Tickell, Kirkby D; Deichsel, Emily L; Walson, Judd L (American Society of Tropical Medicine and Hygiene, 2020-09-01)
    • COVID-19 Vaccine Trial Begins At UMB

      Morrison, Joanne (2020-08-13)
    • Enhanced Recovery After Surgery for Cesarean Delivery Clinical Practice Guideline: Postoperative Interventions

      Wali, Alexandra; Amos, Veronica Y. (2020-05)
      Problem & Purpose: In the United States, the cesarean delivery rate is approximately 32% of all births, with well over a million performed each year. Compared to women who performs spontaneous vaginal births, cesarean deliveries are associated with a prolonged length of stay. These women are usually young and healthy, possess the ability to achieve a rapid recovery, and have a unique incentive to return to their baseline functional capacity in order to care for their newborn. Enhanced Recovery After Surgery (ERAS) is a standardized set of perioperative interventions implemented to improve surgical outcomes, optimize patient care, and reduce hospital costs. Even though there is an enormous amount of evidence to support the improvements ERAS has made for perioperative care pathways among many surgical specialties, obstetrical surgery lacks established protocols based on such principles. The purpose of implementing the ERAS clinical practice guideline (CPG) is to standardize care throughout the perioperative period and optimize recovery for parturients undergoing elective cesarean deliveries. Methods: The CPG was created using high quality evidence and subsequently evaluated by elected stakeholders using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. Dissemination took place following the incorporation of stakeholder recommendations and feedback. A Practitioner Feedback Questionnaire (PFQ) survey following the formal presentation or the CPG during grand rounds was given to anesthesia staff to assess acceptability and usability of the CPG. Results: Feedback received from the AGREE II Tool and PFQ show satisfactory results on the quality, usability, applicability, and acceptance of the CPG. Conclusion: The favorable AGREE II Tool assessment results, widespread acceptance of the interventions among staff as evidenced by the PFQ results, as well as the strength of evidenced utilized to create the recommendations included in the CPG, will facilitate the quality and safety of recovery for elective cesarean deliveries at the institution of interest.
    • Screening for Depression in a Rural Primary Care Setting

      Wallander, Jacquelyn C.; Yarbrough, Karen (2020-05)
      Problem and Purpose: The United States Preventative Services Taskforce recommends depression screening in the general adult population. Patients with untreated depression have higher morbidity rates in many diagnosis groups. Detecting and managing depression allows patients to better self-manage chronic diseases and contributes to an overall sense of improved well-being. In a private primary care setting a practice gap existed in which patients were not routinely screened for depression. The purpose of this quality improvement (QI) project was to implement a screening process for adults in a primary care practice to detect depression symptoms and offer treatment if indicated. Methods: The primary aim of this QI project was to implement a depression screening process for adults in a primary care practice using the Patient Health Questionnaire-9 (PHQ-9), a validated depression screening instrument. Primary outcomes measured: provider compliance in obtaining depression screenings and calculating the percentage of patients identified with depression. Eligible patients were aged 18-64 being seen for an annual exam with two Nurse Practitioners (NP). The NPs were provided PHQ-9 education and weekly reminders to complete the screening. During each patient annual exam, the patient was provided a copy of the PHQ-9. The NP reviewed results and treated when indicated. Charts were audited weekly for: provider compliance and depression classification. Results: Depression screening compliance was 67%, (n=30/45) and 30% of patients screened (n=9/30) were diagnosed with depression. All depressed patients were offered treatment. 20% were new depression diagnoses (n=6/30) and 10% had a history of depression (n=3/30). 13% (n=4/30) of patients were provided referrals to psychotherapy and 7% (n=2/30) were started on a medication for depression. The majority of the positive depression screenings (67%, n=6/9) were detected as mild. Conclusion: Depression screening using the PHQ-9 instrument is an effective way to detect depression. This will reduce the untreated depression rates in the practice and connect patients to proper treatment. Once depression is managed, patients are able to better self-manage chronic diseases. Implementation of the PHQ-9 into the provider workflow will increase depression screening compliance. As a result of this project, the primary care practice built the PHQ-9 instrument into the electronic health record to facilitate provider compliance.
    • Implementation of an Algorithm for Goal-Directed Hemostatic Resuscitation in Trauma

      Westbrook, Lauren M.; Akintade, Bimbola F. (2020-05)
      Problem & Purpose Hemorrhage is the leading preventable cause of death following an injury and causes 30 to 40 percent of all trauma deaths. Trauma patients are highly susceptible to life-threatening coagulopathies which potentiate bleeding and require specialized diagnostics to identify and manage. Thromboelastography (TEG) effectively identifies trauma-induced coagulopathies, and offers customized strategies for hemostatic resuscitation, resulting in less blood product transfused, better survival rates, and shorter lengths of stay. The purpose of this evidence-based quality improvement project was to facilitate the process of goal-directed hemostatic resuscitation in trauma patients requiring massive transfusions by protocoling the use of an algorithm for rapid TEG (rTEG) guided hemostatic resuscitation during massive transfusion events (MTE). Methods For a Level I Trauma Center admitting unit with rTEG capabilities, an evidence-based algorithm for rTEG interpretation and application was modified to include rTEG in the existing MTE criteria. Multi-modal educational resources for rTEG interpretation were provided, and processes impeding unit workflow and practices to facilitate integration of rTEG in to active trauma resuscitation were addressed. Total number of blood products given during MTEs were compared with unpaired T-tests between implementation (September – October 2019) and baseline (September – October 2018) timeframes. Staff perceptions of TEG value and application in trauma were assessed before and after implementation of the algorithm. Results Despite numerous challenges throughout project implementation, staff were significantly more comfortable with interpreting TEGs (p=0.002) and teaching TEG interpretation to other nurses (p=0.04) following implementation of the algorithm. Cryoprecipitate (CRYO) administration increased despite having less MTEs in the implementation period, which may reflect increased awareness of hemostatic resuscitation strategies (ratio of CRYO to MTE in 2018: 0.48; 2019: 0.78). No significant difference was found between the volumes of blood products transfused during implementation and baseline timeframes. Conclusion Algorithmic approaches to rTEG application in trauma resuscitation should be considered to enhance nurses’ confidence in rTEG interpretation. Protocoling the use of TEG in traumarelated MTEs may improve adherence to evidence-based goal-directed hemostatic resuscitation strategies through the use of hemostatic blood products. Point-of-care rTEG procedures require extensive multi-disciplinary collaboration, which can be facilitated by a designated process champion.
    • Bathtime Shenanigans: Implementing Evidence-Based Bathing Practices

      Williams, Keiara D.; Felauer, Ann (2020-05)
      Problem: Bathing practices vary among neonatal intensive care units (NICU), despite guidelines developed by the Association of Women’s Health, Obstetrics and Neonatal Nurses (AWHONN). Bathing should occur allowing for optimal outcomes in the neonate, while attempting to minimize negative physiologic effects due to the stress of bathing. Purpose: The purpose of this project was to implement evidence-based bathing practices in a level IV NICU, where practices vary. Through the utilization of AWHONN’s Neonatal Skin Care Guidelines (NSCG), the goal was to reduce signs of neonatal stress, particularly temperature and behavioral signs of distress during bathing. Methods: The population consisted of neonates ranging in age from 24 to 40 weeks’ gestation in a 52 bed NICU. Implementation occurred over a twelve-week period in the fall of 2019, which included collection of baseline data, identification of unit-based champions, staff education, competency assessments, and development of resources and reminders for staff. Guideline-based algorithms were created, which determined inclusion and exclusion criteria for bathing. Documentation on bedside charts included the age of the infant, the type of bath given, and measures of tolerance to bath assessed by pain/sedation scores and patient temperature 15 minutes post bath. Results: Training resulted in guideline competency among 16% of the NICU nurses. The bedside documentation tool was completely filled out 36 times over the six-week period of implementation, on a unit where the patient census averages 45-52 patients a day. Although, limited, there were some apparent trends in the data that suggests evidence-based bathing practices are needed on this unit. There were no negative effects of increased pain/sedation scores when the infants were swaddle bathed, pain/sedation scores remained < 3, requiring no interventions. Normal temperatures were more likely if the infant was swaddled bathed. However, about 36% of the documented temperatures were <36.5, despite the type the bath. Conclusion: Evidence-based bathing practices help to reduce negative outcomes in the neonatal population. Implementing a practice change within a large unit requires continuing education to enforce the strategies set forth by AWHONN and cement strategies for sustainability and accountability into practice.
    • Let’s Talk: Post Critical Incident Debriefing Project

      Wiseman, Tamara L.; Wise, Barbara V. (2020-05)
      Problem and Purpose: Structured debriefings inconsistently occur in a level IV Neonatal Intensive Care Unit (NICU). Lack of a structured debriefing process negatively impacts provider physical/emotional health and patient outcomes. Lack of debriefing conversations leads to unconstructive feedback and unidentified areas for team and patient outcome improvement. The purpose of this quality improvement (QI) project is to implement, the Team Strategies and Tools to Enhance Performance and Patient Safety Debriefing Tool (TeamSTEPPS) following high-risk deliveries in infants 22-32-week gestation and emergency/resuscitation codes in a 52 bed, level IV NICU in the mid-Atlantic region. The goal is to facilitate debriefings after 100% of the critical events and enhance positive team communication during debriefings. Methods: The project was implemented for 12 weeks. The population included a multidisciplinary NICU staff. The project involved training staff on the use of the standardized debriefing tool, documenting high-risk deliveries, frequency of debriefing guided by the TeamSTEPPS debriefing tool, and evaluating debriefing outcomes using the REFLECT Tool. The primary QI metrics included the number of staff trained and educated, patient gestational age, high-risk delivery and emergency codes, occurrence of debriefing, debriefings guided by TeamSTEPPS Debriefing Tool, and staff assessment of the debriefings using the REFLECT Tool. Data was analyzed using descriptive statistics to identify trends in the percentage of debriefings that occurred following 22-32 weeks gestation deliveries and emergency/resuscitation codes. Results: During implementation phase, twenty percent of the NICU staff were trained/educated in the debriefing process. A total of four debriefings occurred using the TeamSTEPPS Debriefing Tool. Post critical events debriefings increased from one percent to fifteen percent. Team communication, role delineation, and patient stabilization time improved during a subsequent critical event. Conclusions: This QI project demonstrated the feasibility of implementing a structured debriefing tool in a high acuity NICU, to improve team communications and patient outcomes following critical events. Increased nursing and provider staff engagement, and ongoing training would enhance debriefing facilitation. Future considerations include expanding debriefing after all emergent deliveries, including the labor and delivery team, and piloting in smaller NICUs.
    • Improving Allergen Immunotherapy Assessment and Follow-up Utilizing a Screening Tool

      Witt, Ashley A.; Scheu, Karen (2020-05)
      Problem & Purpose: Allergen immunotherapy (AIT) is an effective treatment for environmental allergies and/or allergic asthma involving the administration of subcutaneous injections at regular intervals. Treatment guidelines recommend the routine use of questionnaires and annual follow-up visits to monitor patients’ symptoms, AIT tolerance and efficacy, and guide overall treatment plans. Poor follow-up rates and a lack of routine assessment with screening tools were identified at a suburban Maryland allergy and asthma specialty care clinic. Methods: A pre-screening tool was administered every 4 to 6 weeks prior to AIT injections. The screening included health questions and validated assessments of allergy and/or asthma symptom severity and disease control. Individualized patient follow-up plans were determined based on screening results and evidenced based improvements were also made to patient educational materials, and AIT administration records. Results: Over 14-weeks, 85 adult patients completed a total of 204 screenings. The overall screening completion rate was 86.1%, with 41.2% of screenings identified as positive, and timely appointments scheduled for 66.7% of positive screenings. Overall compliance with AIT follow-up within 12 months improved significantly, from a baseline of 62.35% (n=53), to 98.82% (n=84) over the course of the project (p>0.001). Conclusions: Significant improvements in AIT patient assessment and provider follow-ups were noted during the course of this quality improvement DNP project. These improvements demonstrate that the quality improvement interventions were successful and over time may improve the overall disease management and health outcomes of AIT patients. demonstrating over time that patients may improve their overall disease management and health outcomes.
    • Minimizing pharmacotherapy-related healthcare worker exposure to SARS-CoV-2

      Barlow, Brooke; Barlow, Ashley; Thompson Bastin, Melissa L; Berger, Karen; Dixit, Deepali; Heavner, Mojdeh S (American Society of Health-System Pharmacists, 2020-09-04)
    • The Role of Eicosanoids in Gynecological Malignancies

      Smith, Paige G.; Roque, Dana; Ching, Mc Millan; Fulton, Amy; Rao, Gautam; Reader, Jocelyn C. (Frontiers Media S.A., 2020-08-26)
      Eicosanoids, bio-active lipid molecules, evoke a multitude of biological effects that directly affect cancer cells and indirectly affect tumor microenvironment. An emerging role has been shown for eicosanoids in the pathogenesis of gynecological malignancies which include cancers of the vulva, vagina, cervix, uterine, and ovary. Eicosanoid biosynthesis pathways start at the metabolism of phospholipids by phospholipase A2 then proceeding to one of three pathways: the cyclooxygenase (COX), lipoxygenase (LOX), or P450 epoxygenase pathways. The most studied eicosanoid pathways include COX and LOX; however, more evidence is appearing to support further study of the P450 epoxygenase pathway in gynecologic cancers. In this review, we present the current knowledge of the role of COX, LOX and P450 pathways in the pathogenesis of gynecologic malignancies. Vulvar and vaginal cancer, the rarest subtypes, there is association of COX-2 expression with poor disease specific survival in vulvar cancer and, in vaginal cancer, COX-2 expression has been found to play a role in mucosal inflammation leading to disease susceptibility and transmission. Cervical cancer is associated with COX-2 levels 7.4 times higher than in healthy tissues. Additionally, HPV elevates COX-2 levels through the EGFR pathway and HIV promotes elevated COX-2 levels in cervical tissue as well as increases PGE2 levels eliciting inflammation and progression of cancer. Evidence supports significant roles for both the LOX and COX pathways in uterine cancer. In endometrial cancer, there is increased expression of 5-LOX which is associated with adverse outcomes. Prostanoids in the COX pathway PGE2 and PGF2α have been shown to play a significant role in uterine cancer including alteration of proliferation, adhesion, migration, invasion, angiogenesis, and the inflammatory microenvironment. The most studied gynecological malignancy in regard to the potential role of eicosanoids in tumorigenesis is ovarian cancer in which all three pathways have shown to be associated or play a role in ovarian tumorigenesis directly on the tumor cell or through modulation of the tumor microenvironment. By identifying the gaps in knowledge, additional pathways and targets could be identified in order to obtain a better understanding of eicosanoid signaling in gynecological malignancies and identify potential new therapeutic approaches.
    • Intratumoral generation of photothermal gold nanoparticles through a vectorized biomineralization of ionic gold

      Schwartz-Duval, Aaron S; Konopka, Christian J; Moitra, Parikshit; Daza, Enrique A; Srivastava, Indrajit; Johnson, Elyse V; Kampert, Taylor L; Fayn, Stanley; Haran, Anand; Dobrucki, Lawrence W; et al. (Springer Nature, 2020-09-10)
      Various cancer cells have been demonstrated to have the capacity to form plasmonic gold nanoparticles when chloroauric acid is introduced to their cellular microenvironment. But their biomedical applications are limited, particularly considering the millimolar concentrations and longer incubation period of ionic gold. Here, we describe a simplistic method of intracellular biomineralization to produce plasmonic gold nanoparticles at micromolar concentrations within 30 min of application utilizing polyethylene glycol as delivery vector for ionic gold. We have characterized this process for intracellular gold nanoparticle formation, which progressively accumulates proteins as the ionic gold clusters migrate to the nucleus. This nano-vectorized application of ionic gold emphasizes its potential biomedical opportunities while reducing the quantity of ionic gold and required incubation time. To demonstrate its biomedical potential, we further induce in-situ biosynthesis of gold nanoparticles within MCF7 tumor mouse xenografts which is followed by its photothermal remediation. © 2020, The Author(s).
    • Computed Tomography-Based Radiomics Signature for the Preoperative Differentiation of Pancreatic Adenosquamous Carcinoma From Pancreatic Ductal Adenocarcinoma

      Ren, Shuai; Zhao, Rui; Cui, Wenjing; Qiu, Wenli; Guo, Kai; Cao, Yingying; Duan, Shaofeng; Wang, Zhongqiu; Chen, Rong (Frontiers Media S.A., 2020-08-25)
      Purpose: The purpose was to assess the predictive ability of computed tomography (CT)-based radiomics signature in differential diagnosis between pancreatic adenosquamous carcinoma (PASC) and pancreatic ductal adenocarcinoma (PDAC). Materials and Methods: Eighty-one patients (63.6 ± 8.8 years old) with PDAC and 31 patients (64.7 ± 11.1 years old) with PASC who underwent preoperative CE-CT were included. A total of 792 radiomics features were extracted from the late arterial phase (n = 396) and portal venous phase (n = 396) for each case. Significantly different features were selected using Mann–Whitney U test, univariate logistic regression analysis, and minimum redundancy and maximum relevance method. A radiomics signature was constructed using random forest method, the robustness and the reliability of which was validated using 10-times leave group out cross-validation (LGOCV) method. Results: Seven radiomics features from late arterial phase images and three from portal venous phase images were finally selected. The radiomics signature performed well in differential diagnosis between PASC and PDAC, with 94.5% accuracy, 98.3% sensitivity, 90.1% specificity, 91.9% positive predictive value (PPV), and 97.8% negative predictive value (NPV). Moreover, the radiomics signature was proved to be robust and reliable using the LGOCV method, with 76.4% accuracy, 91.1% sensitivity, 70.8% specificity, 56.7% PPV, and 96.2% NPV. Conclusion: CT-based radiomics signature may serve as a promising non-invasive method in differential diagnosis between PASC and PDAC.
    • Host and Parasite Transcriptomic Changes upon Successive Plasmodium falciparum Infections in Early Childhood

      Bradwell, Katie R; Coulibaly, Drissa; Koné, Abdoulaye K; Laurens, Matthew B; Dembélé, Ahmadou; Tolo, Youssouf; Traoré, Karim; Niangaly, Amadou; Berry, Andrea A; Kouriba, Bourema; et al. (American Society for Microbiology, 2020-08)
      Children are highly susceptible to clinical malaria, and in regions where malaria is endemic, their immune systems must face successive encounters with Plasmodium falciparum parasites before they develop immunity, first against severe disease and later against uncomplicated malaria. Understanding cellular and molecular interactions between host and parasites during an infection could provide insights into the processes underlying this gradual acquisition of immunity, as well as to how parasites adapt to infect hosts that are successively more malaria experienced. Here, we describe methods to analyze the host and parasite gene expression profiles generated simultaneously from blood samples collected from five consecutive symptomatic P. falciparum infections in three Malian children. We show that the data generated enable statistical assessment of the proportions of (i) each white blood cell subset and (ii) the parasite developmental stages, as well as investigations of host-parasite gene coexpression. We also use the sequences generated to analyze allelic variations in transcribed regions and determine the complexity of each infection. While limited by the modest sample size, our analyses suggest that host gene expression profiles primarily clustered by individual, while the parasite gene expression profiles seemed to differentiate early from late infections. Overall, this study provides a solid framework to examine the mechanisms underlying acquisition of immunity to malaria infections using whole-blood transcriptome sequencing (RNA-seq).IMPORTANCE We show that dual RNA-seq from patient blood samples allows characterization of host/parasite interactions during malaria infections and can provide a solid framework to study the acquisition of antimalarial immunity, as well as the adaptations of P. falciparum to malaria-experienced hosts.
    • Role of fever and ambient temperature in COVID-19

      Gul, Muhammad Hamdan; Htun, Zin Mar; Inayat, Asad (Taylor and Francis Inc., 2020-09-09)
    • Virtual grand rounds as a novel means for applicants and programs to connect in the era of COVID-19

      Xu, Linhan; Ambinder, David; Kang, Juhye; Faris, Sarah; Scarpato, Kristen; Moy, Lou; Kobashi, Kathleen; Lemack, Gary; Malik, Rena (Elsevier Ltd., 2020-09-02)
      Background: COVID-19 has disrupted the 2020–2021 residency application cycle with the cancellation of away rotations and in-person interviews. This study seeks to investigate the feasibility and utility of video conferencing technology (VCT) as an opportunity for applicants to interact with faculty from outside programs. Methods: 18 prospective urology applicants were randomized to 6 urology programs to give a virtual grand rounds (VGR) talk. Presentations were recorded and analyzed to determine audience engagement. Students were surveyed regarding perceived utility of VGR. Faculty were surveyed to determine system usability of VCT and ability to evaluate the applicant. Results: 17 students completed the survey, reporting a 100% satisfaction rate with VGR. A majority felt this was a useful way to learn about outside programs. 85 physicians completed the faculty survey, with nearly half feeling confident in their ability to evaluate the applicant. Video transcription data shows sessions were interactive with minimal distractions. Conclusions: VGR can be a useful means for medical students to express interest in programs as well as an additional marker for faculty to evaluate applicants.
    • Coagulopathy and Thrombosis as a Result of Severe COVID-19 Infection: A Microvascular Focus

      Katneni, Upendra K; Alexaki, Aikaterini; Hunt, Ryan C; Schiller, Tal; DiCuccio, Michael; Buehler, Paul W; Ibla, Juan C; Kimchi-Sarfaty, Chava (Thieme, 2020-08-24)
      Coronavirus disease of 2019 (COVID-19) is the clinical manifestation of the respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While primarily recognized as a respiratory disease, it is clear that COVID-19 is systemic illness impacting multiple organ systems. One defining clinical feature of COVID-19 has been the high incidence of thrombotic events. The underlying processes and risk factors for the occurrence of thrombotic events in COVID-19 remain inadequately understood. While severe bacterial, viral, or fungal infections are well recognized to activate the coagulation system, COVID-19-associated coagulopathy is likely to have unique mechanistic features. Inflammatory-driven processes are likely primary drivers of coagulopathy in COVID-19, but the exact mechanisms linking inflammation to dysregulated hemostasis and thrombosis are yet to be delineated. Cumulative findings of microvascular thrombosis has raised question if the endothelium and microvasculature should be a point of investigative focus. von Willebrand factor (VWF) and its protease, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13), play important role in the maintenance of microvascular hemostasis. In inflammatory conditions, imbalanced VWF-ADAMTS-13 characterized by elevated VWF levels and inhibited and/or reduced activity of ADAMTS-13 has been reported. Also, an imbalance between ADAMTS-13 activity and VWF antigen is associated with organ dysfunction and death in patients with systemic inflammation. A thorough understanding of VWF-ADAMTS-13 interactions during early and advanced phases of COVID-19 could help better define the pathophysiology, guide thromboprophylaxis and treatment, and improve clinical prognosis.
    • Climate and season are associated with prevalence and distribution of trans-hemispheric blue crab reovirus (Callinectes sapidus reovirus 1)

      Zhao, Mingli; Behringer, Donald C.; Bojko, Jamie; Kough, Andrew S.; Plough, Louis; dos Santos Tavares, Camila Prestes; Aguilar-Perera, Alfonso; Reynoso, Omar Shamir; Seepersad, Govind; Maharaj, Omardath; et al. (Inter-Research Science Publishing, 2020-08-13)
      Among the many Callinectes spp. across the western Atlantic, the blue crab C. sapidus has the broadest latitudinal distribution, encompassing both tropical and temperate climates. Its life history varies latitudinally, from extended overwintering at high latitudes to year-round activity in tropical locations. Callinectes sapidus reovirus 1 (CsRV1) is a pathogenic virus first described in North Atlantic C. sapidus and has recently been detected in southern Brazil. Little information exists about CsRV1 prevalence at intervening latitudes or in overwintering blue crabs. Using a quantitative reverse transcription PCR (RT-qPCR) method, this study investigated CsRV1 prevalence in C. sapidus across latitudinal differences in temperature and crab life history, as well as in additional Callinectes spp. and within overwintering C. sapidus. CsRV1 prevalence in C. sapidus was significantly correlated with high water temperature and blue crab winter dormancy. Prevalence of CsRV1 in C. sapidus on the mid-Atlantic coast was significantly lower in winter than in summer. CsRV1 infections were not detected in other Callinectes spp. These findings revealed that CsRV1 is present in C. sapidus across their range, but not in other Callinectes species, with prevalence associated with temperature and host life history. Such information helps us to better understand the underlying mechanisms that drive marine virus dynamics under changing environmental conditions. © The authors 2020.
    • A clickable probe for versatile characterization of S-nitrosothiols

      Clements, Jenna L.; Pohl, Franziska; Muthupandi, Pandi; Rogers, Stephen C.; Mao, Jack; Doctor, Allan; Birman, Vladimir B.; Held, Jason M. (Elsevier BV, 2020-10)
      S-nitrosation of cysteine thiols (SNOs), commonly referred to as S-nitrosylation, is a cysteine oxoform that plays an important role in cellular signaling and impacts protein function and stability. Direct labeling of SNOs in cells with the flexibility to perform a wide range of cellular and biochemical assays remains a bottleneck as all SNO-targeted probes to date employ a single analytical modality such as biotin or a specific fluorophore. We therefore developed a clickable, alkyne-containing SNO probe ‘PBZyn’ based on the o-phosphino-benzoyl group warhead that enables multi-modal analysis via click conjugation. We demonstrate the utility of PBZyn to assay SNOs using in situ cellular imaging, protein blotting and affinity purification, as well as mass spectrometry. The flexible PBZyn probe will greatly facilitate investigation into the regulation of SNOs.