Protein sequence landscapes are not so simple: on reference-free versus reference-based inference.

In a recent preprint, Park, Metzger, and Thornton reanalyze 20 empirical protein sequence-function landscapes using a "reference-free analysis" (RFA) method they recently developed. They argue that these empirical landscapes are simpler and less epistatic than earlier work suggested, and attribute the difference to limitations of the methods used in the original analyses of these landscapes, which they claim are more sensitive to measurement noise, missing data, and other artifacts. Here, we show that these claims are incorrect. Instead, we find that the RFA method introduced by Park et al. is exactly equivalent to the reference-based least-squares methods used in the original analysis of many of these empirical landscapes (and also equivalent to a Hadamard-based approach they implement). Because the reanalyzed and original landscapes are in fact identical, the different conclusions drawn by Park et al. instead reflect different interpretations of the parameters describing the inferred landscapes; we argue that these do not support the conclusion that epistasis plays only a small role in protein sequence-function landscapes.

Magnesium-ibogaine therapy in veterans with traumatic brain injuries.

Traumatic brain injury (TBI) is a leading cause of disability. Sequelae can include functional impairments and psychiatric syndromes such as post-traumatic stress disorder (PTSD), depression and anxiety. Special Operations Forces (SOF) veterans (SOVs) may be at an elevated risk for these complications, leading some to seek underexplored treatment alternatives such as the oneirogen ibogaine, a plant-derived compound known to interact with multiple neurotransmitter systems that has been studied primarily as a treatment for substance use disorders. Ibogaine has been associated with instances of fatal cardiac arrhythmia, but coadministration of magnesium may mitigate this concern. In the present study, we report a prospective observational study of the Magnesium-Ibogaine: the Stanford Traumatic Injury to the CNS protocol (MISTIC), provided together with complementary treatment modalities, in 30 male SOVs with predominantly mild TBI. We assessed changes in the World Health Organization Disability Assessment Schedule from baseline to immediately (primary outcome) and 1 month (secondary outcome) after treatment. Additional secondary outcomes included changes in PTSD (Clinician-Administered PTSD Scale for DSM-5), depression (Montgomery-Åsberg Depression Rating Scale) and anxiety (Hamilton Anxiety Rating Scale). MISTIC resulted in significant improvements in functioning both immediately (Pcorrected < 0.001, Cohen's d = 0.74) and 1 month (Pcorrected < 0.001, d = 2.20) after treatment and in PTSD (Pcorrected < 0.001, d = 2.54), depression (Pcorrected < 0.001, d = 2.80) and anxiety (Pcorrected < 0.001, d = 2.13) at 1 month after treatment. There were no unexpected or serious adverse events. Controlled clinical trials to assess safety and efficacy are needed to validate these initial open-label findings. ClinicalTrials.gov registration: NCT04313712 .

The Experience of Living With Polycystic Ovary Syndrome in the Military.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is the most prevalent reproductive endocrinopathy in women, ranging from 5% to 26% depending on diagnostic criteria applied. Common manifestations of PCOS include overweight and obesity, abnormal menstrual cycles, pelvic pain, increased facial and body hair, acne, and infertility. These abnormalities and associated complications have significant military operational and readiness implications. There is a large gap in research regarding active duty servicewomen (ADW) with PCOS. Therefore, the purpose of this study is to describe ADW's experience of living with PCOS and to describe the service-branch-specific differences among these women. MATERIALS AND METHODS: Moderator's guide, audiotapes, transcripts, and field notes. This was a qualitative descriptive study using focus groups and individual interviews. The David Grant Medical Center Institutional Review Board at Travis AFB, CA, USA, approved the study protocol. Women with PCOS were recruited from U.S. Air Force, Army, and Navy locations. Data were analyzed using constant comparative content analysis. RESULTS: Twenty-three servicewomen from 19 occupations across the Army, Navy, Air Force, and Marine Corps participated. Three overarching categories emerged: (1) challenges managing PCOS symptoms, (2) navigating the military health care system, and (3) navigating PCOS as a service member. CONCLUSIONS: Servicewomen may have significant career consequences related to PCOS sequelae, such as overweight, obesity, uncontrolled menstrual cycle, and pain. Managing the myriad of symptoms can distract women while deployed, in austere conditions, or at their home stations. As one of the most common cardiometabolic, reproductive endocrinologic conditions in women, PCOS has not received the attention, awareness, education, or research necessary to sufficiently support ADW with this condition. It is imperative that evidence-based strategies are developed to inform relevant and high-quality care for these warfighters. Future qualitative studies are needed to further describe specific stressors and needs of ADW with PCOS. Future intervention studies are also needed to evaluate effective management options for ADW with PCOS.

Physical Health and Well-being: Updates and the Way Ahead.

INTRODUCTION: The Women in Combat Summit 2021 "Forging the Future: How Women Enhance the Fighting Force" took place during February 9-11, 2021, via a virtual conference platform. The third and final day of the Summit regarded the physical health and well-being of military women and included the topics of urogenital health, nutrition and iron-deficiency anemia, unintended pregnancy and contraception, and traumatic brain injury. MATERIALS AND METHODS: After presentations on the topics earlier, interested conference attendees were invited to participate in focus groups to discuss and review policy recommendations for physical health and well-being in military women. Discussions centered around the topics discussed during the presentations, and suggestions for future Women in Combat Summits were noted. Specifics of the methods of the Summit are presented elsewhere in this supplement. RESULTS: We formulated research and policy recommendations for urogenital health, nutrition and iron-deficiency anemia, contraception and unintended pregnancy, and traumatic brain injury. CONCLUSIONS: In order to continue to develop the future health of military women, health care providers, researchers, and policymakers should consider the recommendations made in this supplement as they continue to build on the state of the science and forge the future.

Preliminary Data on the Impacts of COVID-19 on Filipino Immigrants in Hawai'i.

Racial and ethnic minorities experience high rates of disease morbidity and mortality. Filipinos in Hawai'i have the second-highest coronavirus disease 2019 (COVID-19) cases and deaths. This exploratory study examined barriers to compliance with COVID-19 prevention practices for Filipino immigrants residing in O'ahu and Maui. Cross-sectional data were collected using mixed methods involving surveys and key informant interviews with Filipino community members. Survey responses (n=50) were collected identifying crucial factors to be addressed and preferences for receiving information related to COVID-19. Some Filipino customs and practices were a barrier to complying with COVID-19 prevention practices; nevertheless, cultural sensitivity was stressed for education messaging. In addition, family and community navigators should be equipped with the training and resources to disseminate COVID-19 information within their communities. Attitudinal, cultural, and linguistic barriers to promote health persist for Filipinos in Hawai'i. The COVID-19 pandemic has exacerbated these barriers due to the circulation of misinformation and lack of information among the Filipino communities of O'ahu and Maui regarding COVID-19 and local policies. Culturally appropriate support including providing tailored and linguistically appropriate COVID-19 information is recommended. Equipping or training a household member to help navigate COVID-19 policies as they change aligns with this community's emphasis on familial and social relationships.

Genotype-phenotype landscapes for immune-pathogen coevolution.

Our immune systems constantly coevolve with the pathogens that challenge them, as pathogens adapt to evade our defense responses, with our immune repertoires shifting in turn. These coevolutionary dynamics take place across a vast and high-dimensional landscape of potential pathogen and immune receptor sequence variants. Mapping the relationship between these genotypes and the phenotypes that determine immune-pathogen interactions is crucial for understanding, predicting, and controlling disease. Here, we review recent developments applying high-throughput methods to create large libraries of immune receptor and pathogen protein sequence variants and measure relevant phenotypes. We describe several approaches that probe different regions of the high-dimensional sequence space and comment on how combinations of these methods may offer novel insight into immune-pathogen coevolution.

Retrospective Analysis of Direct-Acting Oral Anticoagulants (DOACs) Initiation Timing and Outcomes After Thrombolysis in High- and Intermediate-Risk Pulmonary Embolism.

Direct-acting oral anticoagulants (DOACs) are prescribed in the treatment of venous thromboembolism, including pulmonary embolism (PE). Evidence is limited regarding the outcomes and optimal timing of DOACs in patients with intermediate- or high-risk PE treated with thrombolysis. We conducted a retrospective analysis of outcomes among patients with intermediate- and high-risk PE who received thrombolysis, by choice of long-term anticoagulant agent. Outcomes of interest included hospital length of stay (LOS), intensive care unit LOS, bleeding, stroke, readmission, and mortality. Descriptive statistics were used to examine characteristics and outcomes among patients, by anticoagulation group. Patients receiving a DOAC (n = 53) had shorter hospital LOS compared to those in warfarin (n = 39) and enoxaparin (n = 10) groups (mean LOS 3.6, 6.3 and 4.5 days, respectively; P < .0001). This single institution retrospective study suggests DOAC initiation <48 h from thrombolysis may result in shorter hospital LOS compared to DOAC initiation ≥48 h (P < .0001). Further larger studies with more robust research methodology are needed to address this important clinical question.

The landscape of antibody binding affinity in SARS-CoV-2 Omicron BA.1 evolution.

The Omicron BA.1 variant of SARS-CoV-2 escapes convalescent sera and monoclonal antibodies that are effective against earlier strains of the virus. This immune evasion is largely a consequence of mutations in the BA.1 receptor binding domain (RBD), the major antigenic target of SARS-CoV-2. Previous studies have identified several key RBD mutations leading to escape from most antibodies. However, little is known about how these escape mutations interact with each other and with other mutations in the RBD. Here, we systematically map these interactions by measuring the binding affinity of all possible combinations of these 15 RBD mutations (215=32,768 genotypes) to 4 monoclonal antibodies (LY-CoV016, LY-CoV555, REGN10987, and S309) with distinct epitopes. We find that BA.1 can lose affinity to diverse antibodies by acquiring a few large-effect mutations and can reduce affinity to others through several small-effect mutations. However, our results also reveal alternative pathways to antibody escape that does not include every large-effect mutation. Moreover, epistatic interactions are shown to constrain affinity decline in S309 but only modestly shape the affinity landscapes of other antibodies. Together with previous work on the ACE2 affinity landscape, our results suggest that the escape of each antibody is mediated by distinct groups of mutations, whose deleterious effects on ACE2 affinity are compensated by another distinct group of mutations (most notably Q498R and N501Y).

Estimated versus observed 10-year atherosclerotic cardiovascular event rates in a rural population-based health initiative: The Heart of New Ulm Project.

Objective: Assess discrepancy between estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk and observed 10-year event rates in a rural population participating in cardiovascular health initiative. Methods: The study included a rural sample of individuals participating in the Heart of New Ulm (HONU), a population-based health initiative aimed at reducing ASCVD risk in a rural community. HONU conducted over 100 baseline screening events with 5221 individuals participating in 2009. For this analysis, we included participants who were aged 40-79 years, free of ASCVD at baseline, and had adequate data to calculate 10-year ASCVD risk. Electronic health record data and state death records were used to determine rates of non-fatal myocardial infarction and stroke, and ASCVD death from 2010-2019. ASCVD event rates were compared to estimated 10-year risks calculated using the Pooled Cohort Equations, stratified by sex and clinically relevant risk categories. Results: The sample (n = 2819, mean ± SD age 56.1 ± 9.9 years, 59.6% female) had a low prevalence of tobacco use (8.1% current smokers) and diabetes (6.5%) and a high prevalence of hypertension (44.4%) and hyperlipidemia (56.6%). The median estimated 10-year ASCVD risk for the entire sample was 5.7% (IQR 2.3-13.5%) with an observed 10-year ASCVD event rate of 3.4%. The largest gap between observed and estimated risk was in those at intermediate/high (≥7.5%) ASCVD risk (median 10-year risk 15.8% [IQR 10.4-29.0], observed ASCVD event rate 6.4%). Conclusio: In a sample of rural participants exposed to a multifaceted ASCVD prevention initiative, observed rates of ASCVD were substantially lower compared to estimated ASCVD risk. The potential for significantly lower than predicted ASCVD event rates in certain populations should be included in the clinician-patient risk discussion.

Hierarchical sequence-affinity landscapes shape the evolution of breadth in an anti-influenza receptor binding site antibody.

Broadly neutralizing antibodies (bnAbs) that neutralize diverse variants of a particular virus are of considerable therapeutic interest. Recent advances have enabled us to isolate and engineer these antibodies as therapeutics, but eliciting them through vaccination remains challenging, in part due to our limited understanding of how antibodies evolve breadth. Here, we analyze the landscape by which an anti-influenza receptor binding site (RBS) bnAb, CH65, evolved broad affinity to diverse H1 influenza strains. We do this by generating an antibody library of all possible evolutionary intermediates between the unmutated common ancestor (UCA) and the affinity-matured CH65 antibody and measure the affinity of each intermediate to three distinct H1 antigens. We find that affinity to each antigen requires a specific set of mutations - distributed across the variable light and heavy chains - that interact non-additively (i.e., epistatically). These sets of mutations form a hierarchical pattern across the antigens, with increasingly divergent antigens requiring additional epistatic mutations beyond those required to bind less divergent antigens. We investigate the underlying biochemical and structural basis for these hierarchical sets of epistatic mutations and find that epistasis between heavy chain mutations and a mutation in the light chain at the VH-VL interface is essential for binding a divergent H1. Collectively, this is the first work to comprehensively characterize epistasis between heavy and light chain mutations and shows that such interactions are both strong and widespread. Together with our previous study analyzing a different class of anti-influenza antibodies, our results implicate epistasis as a general feature of antibody sequence-affinity landscapes that can potentiate and constrain the evolution of breadth.

Continuing the legacy of a military women's health research interest group.

The Military Women's Health Research Interest Group (MWHRIG) was established in 2010. The purpose of the MWHRIG is to support military clinicians and leaders in determining research priorities, and making evidence-based practice and policy decisions relevant to sex- and gender-appropriate healthcare. This article highlights the history of the MWHRIG, and current activities inclusive of research, mentorship, and collaboration. Future activities for the MWHRIG will focus on continued use of a theoretical framework for military women's health research, inclusivity of gender sexual diversity (GSD), and metrics for future success.

Compensatory epistasis maintains ACE2 affinity in SARS-CoV-2 Omicron BA.1.

The Omicron BA.1 variant emerged in late 2021 and quickly spread across the world. Compared to the earlier SARS-CoV-2 variants, BA.1 has many mutations, some of which are known to enable antibody escape. Many of these antibody-escape mutations individually decrease the spike receptor-binding domain (RBD) affinity for ACE2, but BA.1 still binds ACE2 with high affinity. The fitness and evolution of the BA.1 lineage is therefore driven by the combined effects of numerous mutations. Here, we systematically map the epistatic interactions between the 15 mutations in the RBD of BA.1 relative to the Wuhan Hu-1 strain. Specifically, we measure the ACE2 affinity of all possible combinations of these 15 mutations (215 = 32,768 genotypes), spanning all possible evolutionary intermediates from the ancestral Wuhan Hu-1 strain to BA.1. We find that immune escape mutations in BA.1 individually reduce ACE2 affinity but are compensated by epistatic interactions with other affinity-enhancing mutations, including Q498R and N501Y. Thus, the ability of BA.1 to evade immunity while maintaining ACE2 affinity is contingent on acquiring multiple interacting mutations. Our results implicate compensatory epistasis as a key factor driving substantial evolutionary change for SARS-CoV-2 and are consistent with Omicron BA.1 arising from a chronic infection.

Identification of Charcot Foot: A Case Report.

Neuropathy is a painful and potentially devastating complication of diabetes mellitus affecting many patients. Neuropathy can lead to foot ulcers, infections, and subsequent amputations. Nerve damage from peripheral neuropathy may lead to Charcot neuropathic osteoarthropathy, commonly known as Charcot foot. Flesh wounds and weakened bones causing microfractures of the foot and ankle may lead to foot malformations. Early recognition and care are essential for the treatment of Charcot foot and prevention of further injury. This article discusses the use of monofilament testing for diabetic neuropathy, increasing awareness of Charcot foot, and introducing a screening algorithm for Charcot foot.

Boosting psychological change: Combining non-invasive brain stimulation with psychotherapy.

Mental health disorders and substance use disorders are a leading cause of morbidity and mortality worldwide, and one of the most important challenges for public health systems. While evidence-based psychotherapy is generally pursued to address mental health challenges, psychological change is often hampered by non-adherence to treatments, relapses, and practical barriers (e.g., time, cost). In recent decades, Non-invasive brain stimulation (NIBS) techniques have emerged as promising tools to directly target dysfunctional neural circuitry and promote long-lasting plastic changes. While the therapeutic efficacy of NIBS protocols for mental illnesses has been established, neuromodulatory interventions might also be employed to support the processes activated by psychotherapy. Indeed, combining psychotherapy with NIBS might help tailor the treatment to the patient's unique characteristics and therapeutic goal, and would allow more direct control of the neuronal changes induced by therapy. Herein, we overview emerging evidence on the use of NIBS to enhance the psychotherapeutic effect, while highlighting the next steps in advancing clinical and research methods toward personalized intervention approaches.

Improving Identification of Pediatric Emergence Delirium in the Post Anesthesia Care Unit: A Quality Improvement Opportunity.

OBJECTIVE: This article offers a recommendation on how the Pediatric Assessment Emergence Delirium Scale (PAEDS) could be implemented in the post anesthesia care unit (PACU) to improve the assessment and treatment of pediatric emergence delirium (PED). BACKGROUND: PED is an anticipated complication in the PACU characterized by mental confusion, irritability, disorientation, inconsolable crying, and prolonged postanesthetic recovery time. Although it is a short-lived phenomenon, it increases the risk for traumatic injuries and may lead to a decrease in overall parent satisfaction with their child's surgical experience. METHOD: Implementation of the PAEDS in the PACU has the potential to improve the care and safety of the surgical pediatric patient population and could be a catalyst for PED process improvements. This tool has been used in various studies and has demonstrated the validity and reliability in the assessment of emergence delirium. CONCLUSIONS: Clinical use of the PAEDS is not standard of practice, but considering the adverse effects of PED on patients, parents, and medical staff, a PAEDS protocol could be beneficial to the PACU.

Transdiagnostic role of glutamate and white matter damage in neuropsychiatric disorders: A Systematic Review.

Neuropsychiatric disorders including generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ) have been considered distinct categories of diseases despite their overlapping characteristics and symptomatology. We aimed to provide an in-depth review elucidating the role of glutamate/Glx and white matter (WM) abnormalities in these disorders from a transdiagnostic perspective. The PubMed online database was searched for studies published between 2010 and 2021. After careful screening, 401 studies were included. The findings point to decreased levels of glutamate in the Anterior Cingulate Cortex in both SZ and BD, whereas Glx is elevated in the Hippocampus in SZ and MDD. With regard to WM abnormalities, the Corpus Callosum and superior Longitudinal Fascicle were the most consistently identified brain regions showing decreased fractional anisotropy (FA) across all the reviewed disorders, except GAD. Additionally, the Uncinate Fasciculus displayed decreased FA in all disorders, except OCD. Decreased FA was also found in the inferior Longitudinal Fasciculus, inferior Fronto-Occipital Fasciculus, Thalamic Radiation, and Corona Radiata in SZ, BD, and MDD. Decreased FA in the Fornix and Corticospinal Tract were found in BD and SZ patients. The Cingulum and Anterior Limb of Internal Capsule exhibited decreased FA in MDD and SZ patients. The results suggest a gradual increase in severity from GAD to SZ defined by the number of brain regions with WM abnormality which may be partially caused by abnormal glutamate levels. WM damage could thus be considered a potential marker of some of the main neuropsychiatric disorders.

The endoplasmic reticulum proteostasis network profoundly shapes the protein sequence space accessible to HIV envelope.

The sequence space accessible to evolving proteins can be enhanced by cellular chaperones that assist biophysically defective clients in navigating complex folding landscapes. It is also possible, at least in theory, for proteostasis mechanisms that promote strict quality control to greatly constrain accessible protein sequence space. Unfortunately, most efforts to understand how proteostasis mechanisms influence evolution rely on artificial inhibition or genetic knockdown of specific chaperones. The few experiments that perturb quality control pathways also generally modulate the levels of only individual quality control factors. Here, we use chemical genetic strategies to tune proteostasis networks via natural stress response pathways that regulate the levels of entire suites of chaperones and quality control mechanisms. Specifically, we upregulate the unfolded protein response (UPR) to test the hypothesis that the host endoplasmic reticulum (ER) proteostasis network shapes the sequence space accessible to human immunodeficiency virus-1 (HIV-1) envelope (Env) protein. Elucidating factors that enhance or constrain Env sequence space is critical because Env evolves extremely rapidly, yielding HIV strains with antibody- and drug-escape mutations. We find that UPR-mediated upregulation of ER proteostasis factors, particularly those controlled by the IRE1-XBP1s UPR arm, globally reduces Env mutational tolerance. Conserved, functionally important Env regions exhibit the largest decreases in mutational tolerance upon XBP1s induction. Our data indicate that this phenomenon likely reflects strict quality control endowed by XBP1s-mediated remodeling of the ER proteostasis environment. Intriguingly, and in contrast, specific regions of Env, including regions targeted by broadly neutralizing antibodies, display enhanced mutational tolerance when XBP1s is induced, hinting at a role for host proteostasis network hijacking in potentiating antibody escape. These observations reveal a key function for proteostasis networks in decreasing instead of expanding the sequence space accessible to client proteins, while also demonstrating that the host ER proteostasis network profoundly shapes the mutational tolerance of Env in ways that could have important consequences for HIV adaptation.

Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial.

OBJECTIVE: Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing a neuroscience-informed accelerated iTBS protocol, Stanford neuromodulation therapy (SNT; previously referred to as Stanford accelerated intelligent neuromodulation therapy, or SAINT). This protocol was associated with a remission rate of ∼90% after 5 days of open-label treatment. Here, the authors report the results of a sham-controlled double-blind trial of SNT for treatment-resistant depression. METHODS: Participants with treatment-resistant depression currently experiencing moderate to severe depressive episodes were randomly assigned to receive active or sham SNT. Resting-state functional MRI was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The primary outcome was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 4 weeks after treatment. RESULTS: At the planned interim analysis, 32 participants with treatment-resistant depression had been enrolled, and 29 participants who continued to meet inclusion criteria received either active (N=14) or sham (N=15) SNT. The mean percent reduction from baseline in MADRS score 4 weeks after treatment was 52.5% in the active treatment group and 11.1% in the sham treatment group. CONCLUSIONS: SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation for treatment-resistant depression. Further trials are needed to determine SNT's durability and to compare it with other treatments.

Integrative Review of Racial Disparities in Perinatal Outcomes Among Beneficiaries of the Military Health System.

OBJECTIVE: To examine the extent to which racial disparities exist in the perinatal outcomes of beneficiaries of the Military Health System (MHS). DATA SOURCES: We searched the PubMed, CINAHL, and Embase databases. STUDY SELECTION: We selected articles published in English in peer-reviewed journals in which the authors examined race in relation to perinatal outcomes among beneficiaries of the MHS. Date of publication was unrestricted through March 2021. DATA EXTRACTION: Twenty-six articles met the inclusion criteria. We extracted data about study design, purpose, sample, setting, and results. We also assigned quality appraisal ratings to each article. DATA SYNTHESIS: In most of the included articles, researchers observed differences in perinatal outcomes between Black and White women. Compared to White women, Black women had greater rates of cesarean birth, preterm birth, low birth weight, and small for gestational age neonates. White women had greater rates of postpartum depression than Black women. CONCLUSION: Racial disparities in very low birth weight newborns and preterm birth may be smaller in the MHS than in the general population of the United States. The overall rates of preterm birth, cesarean birth, and neonatal mortality were lower for beneficiaries of the MHS than in the general population of the United States.

Scoping Review on Menstrual Suppression Among U.S. Military Service Members.

INTRODUCTION: The purpose of this scoping review was to systematically evaluate literature addressing menstrual suppression in the military population and to identify gaps in the literature. MATERIALS AND METHODS: A scoping review of the literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines was completed. Quality appraisal was conducted using the Johns Hopkins Evidence-Based Practice (EBP) Evidence Level and Quality Guide. RESULTS: Thirteen research articles and nine non-research articles were included. The themes identified were methods for menstrual suppression, barriers to menstrual suppression, and educational recommendations. CONCLUSIONS: Six gaps were identified: (1) readiness, (2) single branch of service, (3) options for suppression, (4) hesitance to suppress, (5) provider practices, and (6) stagnant research. Recommendations for future research, practice, and military health policy are provided. Expanding research on menstrual suppression in U.S. military service members will enhance the health of military service members, provider practices, and military health policy to promote military readiness.