scL-2PAM: A Novel Countermeasure That Ameliorates Neuroinflammation and Neuronal Losses in Mice Exposed to an Anticholinesterase Organophosphate.

Due to their inhibition of acetylcholinesterase, organophosphates are among the most toxic of chemicals. Pralidoxime (a.k.a 2-PAM) is the only acetylcholinesterase reactivator approved in the U.S., but 2-PAM only poorly traverses the blood-brain barrier. Previously, we have demonstrated that scL-2PAM, a nanoformulation designed to enter the brain via receptor-mediated transcytosis, is superior to unencapsulated 2-PAM for reactivating brain acetylcholinesterase, ameliorating cholinergic crisis, and improving survival rates for paraoxon-exposed mice. Here, we employ histology and transcriptome analyses to assess the ability of scL-2PAM to prevent neurological sequelae including microglial activation, expression of inflammatory cytokines, and ultimately loss of neurons in mice surviving paraoxon exposures. Levels of the mRNA encoding chemokine ligand 2 (CCL2) were significantly upregulated after paraoxon exposures, with CCL2 mRNA levels in the brain correlating well with the intensity and duration of cholinergic symptoms. Our nanoformulation of 2-PAM was found to be superior to unencapsulated 2-PAM in reducing the levels of the CCL2 transcript. Moreover, brain histology revealed that scL-2PAM was more effective than unencapsulated 2-PAM in preventing microglial activation and the subsequent loss of neurons. Thus, scL-2PAM appears to be a new and improved countermeasure for reducing neuroinflammation and mitigating brain damage in survivors of organophosphate exposures.

Novel clinical risk stratification and treatment strategies in relapsed/refractory peripheral T-cell lymphoma.

Peripheral T cell lymphoma (PTCL) represents a group of heterogeneous hematological malignancies, which are notoriously challenging to treat and outcomes are typically poor. Over the past two decades, clinical prognostic indices for patient risk stratification have evolved, while several targeted agents are now available to complement combination chemotherapy in the frontline setting or as a salvage strategy. With further understanding of the molecular pathobiology of PTCL, several innovative approaches incorporating immunomodulatory agents, epigenetic therapies, oncogenic kinase inhibitors and immunotherapeutics have come to the forefront. In this review, we provide a comprehensive overview of the progress in developing clinical prognostic indices for PTCL and describe the broad therapeutic landscape, emphasizing novel targetable pathways that have entered early phase clinical studies.

SMARCB1 Gene Therapy Using a Novel Tumor-Targeted Nanomedicine Enhances Anti-Cancer Efficacy in a Mouse Model of Atypical Teratoid Rhabdoid Tumors.

Purpose: Atypical teratoid rhabdoid tumor (ATRT) is a deadly, fast-growing form of pediatric brain cancer with poor prognosis. Most ATRTs are associated with inactivation of SMARCB1, a subunit of the chromatin remodeling complex, which is involved in developmental processes. The recent identification of SMARCB1 as a tumor suppressor gene suggests that restoration of SMARCB1 could be an effective therapeutic approach. Methods: We tested SMARCB1 gene therapy in SMARCB1-deficient rhabdoid tumor cells using a novel tumor-targeted nanomedicine (termed scL-SMARCB1) to deliver wild-type SMARCB1. Our nanomedicine is a systemically administered immuno-lipid nanoparticle that can actively cross the blood-brain barrier via transferrin receptor-mediated transcytosis and selectively target tumor cells via transferrin receptor-mediated endocytosis. We studied the antitumor activity of the scL-SMARCB1 nanocomplex either as a single agent or in combination with traditional treatment modalities in preclinical models of SMARCB1-deficient ATRT. Results: Restoration of SMARCB1 expression by the scL-SMARCB1 nanocomplex blocked proliferation, and induced senescence and apoptosis in ATRT cells. Systemic administration of the scL-SMARCB1 nanocomplex demonstrated antitumor efficacy as monotherapy in mice bearing ATRT xenografts, where the expression of exogenous SMARCB1 modulates MYC-target genes. scL-SMARCB1 demonstrated even greater antitumor efficacy when combined with either cisplatin-based chemotherapy or radiation therapy, resulting in significantly improved survival of ATRT-bearing mice. Conclusion: Collectively, our data suggest that restoring SMARCB1 function via the scL-SMARCB1 nanocomplex may lead to therapeutic benefits in ATRT patients when combined with traditional chemoradiation therapies.

Recent updates on central nervous system prophylaxis in patients with high-risk diffuse large B-cell lymphoma.

The use of central nervous system (CNS) prophylaxis for patients with diffuse large B-cell lymphoma (DLBCL) remains controversial. Although uncommon, CNS relapses are invariably fatal in this otherwise curable disease. Accurate identification of patients at risk and the optimal approach to CNS prophylaxis therefore remains an area of unmet need. The existing literature, largely retrospective in nature, provides mixed conclusions regarding the efficacy of CNS prophylaxis. The utility of CNS prophylaxis has itself been challenged. In this review, we dissect the issues which render the value of CNS prophylaxis uncertain. We first compare international clinical guidelines for CNS prophylaxis. We then interrogate the factors that should be used to identify high-risk patients accurately. We also explore how clinical patterns of CNS relapse have changed in the pre-rituximab and rituximab era. We then discuss the efficacy of CNS-directed approaches, intensification of systemic treatment and other novel approaches in CNS prophylaxis. Improved diagnostics for early detection of CNS relapses and newer therapeutics for CNS prophylaxis are areas of active investigation. In an area where prospective, randomized studies are impracticable and lacking, guidance for the use of CNS prophylaxis will depend on rigorous statistical review of retrospective data.

A Pralidoxime Nanocomplex Formulation Targeting Transferrin Receptors for Reactivation of Brain Acetylcholinesterase After Exposure of Mice to an Anticholinesterase Organophosphate.

Introduction: Organophosphates are among the deadliest of known chemicals based on their ability to inactivate acetylcholinesterase in neuromuscular junctions and synapses of the central and peripheral nervous systems. The consequent accumulation of acetylcholine can produce severe acute toxicities and death. Oxime antidotes act by reactivating acetylcholinesterase with the only such reactivator approved for use in the United States being 2-pyridine aldoxime methyl chloride (a.k.a., pralidoxime or 2-PAM). However, this compound does not cross the blood-brain barrier readily and so is limited in its ability to reactivate acetylcholinesterase in the brain. Methods: We have developed a novel formulation of 2-PAM by encapsulating it within a nanocomplex designed to cross the blood-brain barrier via transferrin receptor-mediated transcytosis. This nanocomplex (termed scL-2PAM) has been subjected to head-to-head comparisons with unencapsulated 2-PAM in mice exposed to paraoxon, an organophosphate with anticholinesterase activity. Results and Discussion: In mice exposed to a sublethal dose of paraoxon, scL-2PAM reduced the extent and duration of cholinergic symptoms more effectively than did unencapsulated 2-PAM. The scL-2PAM formulation was also more effective than unencapsulated 2-PAM in rescuing mice from death after exposure to otherwise-lethal levels of paraoxon. Improved survival rates in paraoxon-exposed mice were accompanied by a higher degree of reactivation of brain acetylcholinesterase. Conclusion: Our data indicate that scL-2PAM is superior to the currently used form of 2-PAM in terms of both mitigating paraoxon toxicity in mice and reactivating acetylcholinesterase in their brains.

Clinical features and prognostic outcomes of angioimmunoblastic T cell lymphoma in an Asian multicenter study.

In our Asian multicenter retrospective study, we investigated the clinical prognostic factors affecting the outcomes of AITL patients and identified a novel prognostic index relevant in the Asian context. In our 174-patient cohort, the median PFS and OS was 1.8 years and 5.6 years respectively. Age > 60, bone marrow involvement, total white cell count >12 × 109/L and raised serum lactate dehydrogenase were associated with poorer PFS and OS in multivariate analyses. This allowed for a prognostic index (AITL-PI) differentiating patients into low (0-1 factors, n = 64), moderate (2 factors, n = 59) and high-risk (3-4 factors, n = 49) subgroups with 5-year OS of 84.0%, 44.0% and 28.0% respectively (p < 0.0001). POD24 proved to be strongly prognostic (5-year OS 24% vs 89%, p < 0.0001). Exploratory gene expression studies were performed and disparate immune cell profiles and cell signaling signatures were seen in the low risk group as compared to the intermediate and high risk groups.

Post-Treatment Neutrophil and Lymphocyte Counts Predict Progression-Free Survival Following First-Line Chemotherapy in Hodgkin's Lymphoma.

Hodgkin's lymphoma carries an excellent prognosis with modern chemotherapy, but a significant proportion of patients remain refractory to or relapse after first-line treatment. Immunological changes post-treatment, such as chemotherapy-induced neutropenia (CIN) or lymphopenia, have shown prognostic significance in multiple tumor types. Our study aims to investigate the prognostic value of immunologic changes in Hodgkin's lymphoma by examining the post-treatment lymphocyte count (pALC), neutrophil count (pANC) and the neutrophil-lymphocyte ratio (pNLR). Patients treated for classical Hodgkin's lymphoma at the National Cancer Centre Singapore using ABVD-based regimens were retrospectively analyzed. An optimal cut-off value for high pANC, low pALC and high pNLR in predicting progression-free survival was determined by receiver operating curve analysis. Survival analysis was performed using the Kaplan-Meier method and multivariable Cox proportional models. Overall OS and PFS were excellent, with a 5-year OS of 99.2% and a 5-year PFS of 88.2%. Poorer PFS was associated with high pANC (HR 2.99, p = 0.0392), low pALC (HR 3.95, p = 0.0038) and high pNLR (p = 0.0078). In conclusion, high pANC, low pALC and high pNLR confer a poorer prognosis for Hodgkin's lymphoma. Future studies should evaluate the potential of improving treatment outcomes by the adjustment of chemotherapy dose intensity based on post-treatment blood counts.

The mother-daughter Shared Agency in Weight Management Scale (SAWMS): development, validation, and implications for body dissatisfaction.

BACKGROUND: Much research suggests that mothers play an important role in shaping daughters' body image, yet less is known about how mother-daughter relationship dynamics in weight management affect daughters' body dissatisfaction. The current paper described the development and validation of the mother-daughter Shared Agency in Weight Management Scale (SAWMS) and examined its associations with daughter's body dissatisfaction. METHODS: In Study 1 (N = 676 college students), we explored the factor structure of the mother-daughter SAWMS and identified three processes (control, autonomy support, and collaboration) whereby mothers work with daughters in weight management. In Study 2 (N = 439 college students), we finalized the factor structure of the scale by conducting two CFAs and assessing the test-retest reliability of each subscale. In Study 3 (same sample as Study 2), we examined the psychometric properties of the subscales and their associations with daughters' body dissatisfaction. RESULTS: Combining results from EFA and IRT, we identified three mother-daughter dynamics in weight management-maternal control, maternal autonomy support, and maternal collaboration. However, based on various empirical results indicating poor psychometric properties of the maternal collaboration subscale, we removed it from the mother-daughter SAWMS and only evaluated the psychometric properties of the remaining two subscales (i.e., control and autonomy support). They explained a significant amount of variance in daughters' body dissatisfaction over and above the effect of maternal pressure to be thin. Maternal control was a significant and positive predictor of daughters' body dissatisfaction; maternal autonomy support was a significant and negative predictor. CONCLUSIONS: Results suggested that maternal control in weight management was associated with daughters' increased body dissatisfaction, whereas maternal autonomy support in weight management was associated with daughters' lower body dissatisfaction. These specific ways in which mother work with daughters in weight management provide nuances in understanding young women's body dissatisfaction. Our SAWMS offers new ways to examine body image among young women through the mother-daughter relationship dynamics in weight management.

The current study described the procedure of developing a new measurement­the mother­daughter Shared Agency in Weight Management Scale (SAWMS). This scale aims to measure the different ways in which mothers work with their cisgender daughters in weight management. Based on self-reported survey data from cisgender female college students, we identified two ways whereby mothers work with their daughters in weight management­maternal control and maternal autonomy support. To better understand these mother­daughter dynamics, we also examined their relations with daughter's body dissatisfaction. We found that daughters whose mothers were more controlling when it comes to weight management reported higher levels of body dissatisfaction. On the other hand, daughters whose mothers were more autonomy-supportive in weight management reported lower levels of body dissatisfaction. Our results have important implications for understanding how mother­daughter relationship dynamics in weight management may contribute to the development of body image and perceptions among young women.

Burkitt lymphoma - no impact of HIV status on outcomes with rituximab-based chemoimmunotherapy.

We analyzed the prognostic factors for treatment outcomes amongst 34 patients with adult Burkitt lymphoma (BL) who received rituximab with standard first-line chemotherapy. Seven patients had human immunodeficiency virus (HIV)-associated BL. Overall, we observed a complete remission (CR) rate of 91.2%, and 10-year progression-free survival (PFS) and overall survival (OS) was 84.8 and 88.2%, respectively. In patients with concomitant HIV, the prognosis was not different with 10-year PFS of 100% and OS of 88.2%. The majority (71.4%) of HIV-associated BL patients received dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) and had excellent outcomes with 100% CR and no relapses. Central nervous system (CNS) disease, bone marrow involvement and elevated serum lactate dehydrogenase (LDH) levels more than 3 times upper limit of normal (ULN) were associated with poorer survival outcomes. Patients with refractory disease, whilst uncommon (n = 4), had dismal outcomes. Patients with adult BL, including HIV-related cases, harbor generally good prognosis in the modern era.

Implementing a Spiritual Care Subject for Holistic Nursing Practice: A Mixed Method Study.

Aim: The aims of this sequential explanatory mixed method study were twofold 1. Firstly, to evaluate the implementation of a spiritual care subject in a nursing program. 2. Secondly, to examine undergraduate nursing students' perceptions of providing spiritual care within their holistic care practice. Background: Studies conducted internationally indicate many nurses feel inadequately prepared to provide holistic care inclusive of spiritual care due to insufficient spiritual care education. Design: Two phase, sequential explanatory mixed method design which comprised of a quantitative study followed by a qualitative study. Methods: The setting was an Australian faith-based university. Participants comprised of undergraduate nursing students who were enrolled in a spiritual care subject. Findings: Two study findings emerged: 1. Participants' knowledge and practice of spiritual care were transformed by the spiritual care subject, and 2. The spiritual care subject broadened perceptions of spiritual care so participants viewed themselves more equipped to provide spiritual care in their holistic care provision. Conclusion: The spiritual care subject had an affirmative influence on participants' perceptions of providing spiritual care within holistic care practice. The findings have implications for nurse educators to consider how spiritual care content can be included within undergraduate nursing curricula.

Shared and nonshared agency for occupational goals with mothers, fathers, VIPs, and romantic partners during young adulthood.

This study applied a framework of shared and nonshared agency to investigate how social partners can help and hinder young adults' career development. We also considered the extent to which motivational control could be promoted or burdened when young people seek help and encouragement from others in their careers. Based on the importance of shared agency in life goal pursuit, it was hypothesized that shared agency (i.e., perceived support and collaboration) with mothers, fathers, important adults, and romantic partners would have direct and positive associations with young adults' career satisfaction and exploration and positive indirect associations on career development via motivational control. We further hypothesized that nonshared agency (i.e., directing and uninvolvement) would have direct and negative effects on career satisfaction and exploration and negative indirect effects on career development via motivational strategies. Results indicated that relationships can facilitate career development but differently depending upon relationship type. We found that support and directing from mothers and VIPs had positive associations with outcomes via individual motivational control whereas a total effect of collaboration with fathers and romantic partners were associated with outcomes without an indirect effect via motivational control. These findings are discussed within the context of previous socialization research and theory.

A Novel P53 Nanomedicine Reduces Immunosuppression and Augments Anti-PD-1 Therapy for Non-Small Cell Lung Cancer in Syngeneic Mouse Models.

Lung cancer is among the most common and lethal cancers and warrants novel therapeutic approaches to improving patient outcomes. Although immune checkpoint inhibitors (ICIs) have demonstrated substantial clinical benefits, most patients remain unresponsive to currently approved ICIs or develop resistance after initial response. Many ongoing clinical studies are investigating combination therapies to address the limited efficacy of ICIs. Here, we have assessed whether p53 gene therapy via a tumor-targeting nanomedicine (termed SGT-53) can augment anti-programmed cell death-1 (PD-1) immunotherapy to expand its use in non-responding patients. Using syngeneic mouse models of lung cancers that are resistant to anti-PD-1, we demonstrate that restoration of normal p53 function potentiates anti-PD-1 to inhibit tumor growth and prolong survival of tumor-bearing animals. Our data indicate that SGT-53 can restore effective immune responses against lung cancer cells by reducing immuno-suppressive cells (M2 macrophages and regulatory T cells) and by downregulating immunosuppressive molecules (e.g., galectin-1, a negative regulator of T cell activation and survival) while increasing activity of cytotoxic T cells. These results suggest that combining SGT-53 with anti-PD-1 immunotherapy could increase the fraction of lung cancer patients that responds to anti-PD-1 therapy and support evaluation of this combination particularly in patients with ICI-resistant lung cancers.

Nanomedicine-Based Gene Delivery for a Truncated Tumor Suppressor RB94 Promotes Lung Cancer Immunity.

Because lung cancer remains the most common and lethal of cancers, novel therapeutic approaches are urgently needed. RB94 is a truncated form of retinoblastoma tumor suppressor protein with elevated anti-tumor efficacy. Our investigational nanomedicine (termed scL-RB94) is a tumor-targeted liposomal formulation of a plasmid containing the gene encoding RB94. In this research, we studied anti-tumor and immune modulation activities of scL-RB94 nanocomplex in preclinical models of human non-small cell lung cancer (NSCLC). Systemic treatment with scL-RB94 of mice bearing human NSCLC tumors significantly inhibited tumor growth by lowering proliferation and increasing apoptosis of tumor cells in vivo. scL-RB94 treatment also boosted anti-tumor immune responses by upregulating immune recognition molecules and recruiting innate immune cells such as natural killer (NK) cells. Antibody-mediated depletion of NK cells blunted the anti-tumor activity of scL-RB94, suggesting that NK cells were crucial for the observed anti-tumor activity in these xenograft models. Treatment with scL-RB94 also altered the polarization of tumor-associated macrophages by reducing immune-suppressive M2 macrophages to lower immune suppression in the tumor microenvironment. Collectively, our data suggest that the efficacy of scL-RB94 against NSCLC is due to an induction of tumor cell death as well as enhancement of innate anti-tumor immunity.

A Prognostic Model Using Post-Steroid Neutrophil-Lymphocyte Ratio Predicts Overall Survival in Primary Central Nervous System Lymphoma.

Background: Ratios of differential blood counts (hematological indices, HIs) had been identified as prognostic variables in various cancers. In primary central nervous system lymphomas (PCNSLs), higher baseline neutrophil-lymphocyte ratio (NLR) in particular was found to portend a worse overall survival. However, it was often observed that differential counts shift drastically following steroid administration. Moreover, steroids are an important part of the arsenal against PCNSL due to its potent lymphotoxic effects. We showed that the effect of steroids on differential blood cell counts and HIs could be an early biomarker for subsequent progression-free (PFS) and overall survival (OS). Methods: This study retrospectively identified all adult patients who received a brain biopsy from 2008 to 2019 and had histologically confirmed PCNSL, and included only those who received chemoimmunotherapy, with documented use of corticosteroids prior to treatment induction. Different blood cell counts and HIs were calculated at three time-points: baseline (pre steroid), pre chemoimmunotherapy (post steroid) and post chemoimmunotherapy. Tumor progression and survival data were collected and analyzed through Kaplan−Meier estimates and Cox regression. We then utilized selected variables found to be significant on Kaplan−Meier analysis to generate a decision-tree prognostic model, the NNI-NCCS score. Results: A total of 75 patients who received chemoimmunotherapy were included in the final analysis. For NLR, OS was longer with higher pre-chemoimmunotherapy (post-steroid) NLR (dichotomized at NLR ≥ 4.0, HR 0.42, 95% CI: 0.21−0.83, p = 0.01) only. For platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR), OS was better for lower post-chemoimmunotherapy PLR (dichotomized at PLR ≥ 241, HR 2.27, 95% CI: 1.00 to 5.18, p = 0.05) and lower pre-chemoimmunotherapy (post-steroid) LMR (dichotomized at LMR ≥25.7, HR 2.17, 95% CI: 1.10 to 4.31, p = 0.03), respectively, only. The decision-tree model using age ≤70, post-steroid NLR >4.0, and pre-steroid (baseline) NLR <2.5 and the division of patients into three risk profiles­low, medium, and high­achieved good accuracy (area-under-curve of 0.78), with good calibration (Brier score: 0.16) for predicting 2-year overall survival. Conclusion: We found that post-steroid NLR, when considered together with baseline NLR, has prognostic value, and incorporation into a prognostic model allowed for accurate and well-calibrated stratification into three risk groups.

TP53 Gene Therapy as a Potential Treatment for Patients with COVID-19.

SGT-53 is a novel investigational agent that comprises an immunoliposome carrying a plasmid vector driving expression of the human TP53 gene that encodes wild-type human p53. SGT-53 is currently in phase II human trials for advanced pancreatic cancer. Although p53 is best known as a tumor suppressor, its participation in both innate and adaptive immune responses is well documented. It is now clear that p53 is an important component of the host response to various viral infections. To facilitate their viral life cycles, viruses have developed a diverse repertoire of strategies for counteracting the antiviral activities of host immune system by manipulating p53-dependent pathways in host cells. Coronaviruses reduce endogenous p53 levels in the cells they infect by enhancing the degradation of p53 in proteasomes. Thus, interference with p53 function is an important component in viral pathogenesis. Transfection of cells by SGT-53 has been shown to transiently produce exogenous p53 that is active as a pleiotropic transcription factor. We herein summarize the rationale for repurposing SGT-53 as a therapy for infection by SARS-CoV-2, the pathogen responsible for the COVID-19 pandemic. Because p53 regulation was found to play a crucial role in different infection stages of a wide variety of viruses, it is rational to believe that restoring p53 function based on SGT-53 treatment may lead to beneficial therapeutic outcomes for infectious disease at large including heretofore unknown viral pathogens that may emerge in the future.

Treatment outcomes of T and natural-killer/T-cell lymphoma with ifosfamide, carboplatin and etoposide chemotherapy.

BACKGROUND: Contemporary data of peripheral T-cell lymphoma (PTCL) and natural-killer/T-cell lymphoma (NKTL) patients treated with ifosfamide, carboplatin and etoposide (ICE) are limited. AIMS: We performed a retrospective analysis to estimate outcomes of ICE-treated PTCL and NKTL patients at three tertiary cancer centres in Singapore. METHODS AND RESULTS: Patients were identified through lymphoma databases from National Cancer Centre Singapore (NCCS), National University Hospital, Singapore (NUHS), and Singapore General Hospital (SGH). Responses and survival outcomes were determined from electronic medical records. A total of 75 patients with a median age of 50 were included. ICE was used as first-line treatment in 14 patients (19%) and as subsequent lines of treatment in 61 patients (81%). The overall response rates (ORR) for all patients was 63% (40% complete response [CR]). The ORR and CR in the first line were 86% and 64% respectively. At a median follow-up duration of 71.0 months, the median progression-free (PFS) and overall survival (OS) for all patients were 4.4 months (95%CI, 2.7-6.0) and 16 months (95%CI, 8.3-45.4) respectively. CONCLUSION: In summary, ICE showed high ORR but poor PFS in relapsed/refractory PTCL and NKTL. ORR of ICE in the first line setting appears better than real-world CHOP data and warrants further study.

Prognostication of diffuse large B-cell lymphoma patients with Deauville score of 3 or 4 at end-of-treatment PET evaluation: a comparison of the Deauville 5-point scale and the ΔSUVmax method.

Diffuse large B-cell lymphoma is treated with anti-CD 20 and multi-drug chemotherapy for cure. Positron emission tomography (PET) scans are performed at end of treatment (EOT) to assess response. EOT Deauville scores (DS) are equivocal for treatment response in some situations, requiring physicians to determine the need for further investigations or treatment. Studies have suggested the delta maximum standardised uptake value (ΔSUVmax) to be superior to DS for assessment of metabolic response at interim PET, although its use at EOT PET, especially in cases of equivocal response, has yet to be established. We investigated whether ΔSUVmax could better discriminate prognosis than DS 3 or 4 at EOT. ΔSUVmax did not outperform DS. Combination of DS 3 and International Prognostic Index (IPI) <3 selects for patients with extremely low risk of disease progression (HR 0.06, 95% CI 0.01 to 0.62, p 0.018) compared to DS 4 and IPI ≥3.

Spirituality and Standards for Practice: A Critical Discourse Analysis.

Research Objective: The aim of this article is to report a study that explores how spirituality is understood to be represented in the current Australian Nursing and Midwifery Board of Australia (NMBA) Registered Nurse (RN) standards for practice. Research Design: Fairclough's approach to critical discourse analysis was applied in the examination of participant interview texts for the language used in relation to spirituality as well as power mechanisms which influenced the way the participants viewed spirituality's representation in the RN Standards for Practice. Participants: Three members of the RN Standards for Practice research and development team. Results: Findings indicate three discourses shaped the way participants viewed how spirituality is presently represented in the RN Standards for Practice. Discourses are (1) spirituality as part of holistic care, (2) spirituality as part of person-centered care, and (3) the professionalization of nursing. Conclusions: Participant interviews revealed these discourses exerted power over how spirituality was represented within the RN Standards for Practice. This has implications for the inclusion of spirituality in the practice standards and the practice of spiritual care.