An Exploratory Study of an Online Vaccine Education Program in Middle-School Students to Promote Vaccine Acceptance.

Background: While vaccines have reduced the incidence of vaccine-preventable diseases, vaccine hesitancy threatens the re-emergence of childhood infectious diseases. Purpose: This randomized controlled study evaluated an online vaccine education program to advance vaccine acceptance among middle-school students. Methodology: Study participants were randomly assigned to an intervention group who viewed the VEP videos or to a comparison group who viewed a science-based video unrelated to vaccines. Results: Knowledge scores improved in both groups and more favorable shifts in vaccine-related beliefs and attitudes occurred in the intervention than in the comparison group. Conclusions: This program can be feasibly delivered via an online platform to middle school students, resulting in shifts in vaccine-related knowledge, beliefs and attitudes. Implications: Delivering evidence-based content to instruct about vaccine effectiveness and safety is an area in which school nurses have demonstrated an important role as a resource for patient education to promote vaccine advocacy.

Molecular cell biology of complement membrane attack.

The membrane attack complex (MAC) is the pore-forming toxin of the complement system, a relatively early evolutionary acquisition that confers upon complement the capacity to directly kill pathogens. The MAC is more than just a bactericidal missile, having the capacity when formed on self-cells to initiate a host of cell activation events that can have profound consequences for tissue homeostasis in the face of infection or injury. Although the capacity of complement to directly kill pathogens has been recognised for over a century, and the pore-forming killing mechanism for at least 50 years, there remains considerable uncertainty regarding precisely how MAC mediates its killing and cell activation activities. A recent burst of new information on MAC structure provides context and opportunity to re-assess the ways in which MAC kills bacteria and modulates cell functions. In this brief review we will describe key aspects of MAC evolution, function and structure and seek to use the new structural information to better explain how the MAC works.

Conditional Recommendations for Specific Dietary Ingredients as an Approach to Chronic Musculoskeletal Pain: Evidence-Based Decision Aid for Health Care Providers, Participants, and Policy Makers.

OBJECTIVE: Approximately 55-76% of Service members use dietary supplements for various reasons; although such use has become popular for a wide range of pain conditions, decisions to use supplements are often driven by information that is not evidence-based. This work evaluates whether the current research on dietary ingredients for chronic musculoskeletal pain provides sufficient evidence to inform decisions for practice and self-care, specifically for Special Operations Forces personnel. METHODS: A steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. GRADE was used to determine confidence in the effect estimates. A decision table was constructed to make evidence-informed judgments across factors required for decision-making, and recommendations were made for practice and self-care use. RESULTS: Nineteen dietary ingredients were included. Conditional evidence-based recommendations were made for the use of avocado soybean unsaponifiables, capsaicin, curcuma, ginger, glucosamine, melatonin, polyunsaturated fatty acids, and vitamin D. In these cases, desirable effects outweighed undesirable effects, but there was uncertainty about the trade-offs, either because the evidence was low quality or because benefits and downsides were closely balanced. CONCLUSIONS: The evidence showed that certain dietary ingredients, when taken as part of a balanced diet and/or as a supplement (e.g., pill, tablet, capsule, cream), may alleviate musculoskeletal pain with no to minimal risk of harm. This finding emphasizes and reinforces the critical importance of shared decision-making between Operators and their health care providers.

Dietary Ingredients Requiring Further Research Before Evidence-Based Recommendations Can Be Made for Their Use as an Approach to Mitigating Pain.

OBJECTIVE: Approximately 55-76% of Service members use dietary supplements for various reasons; although such use has become popular, decisions are often driven by information that is not evidence-based. This work evaluates whether current research on dietary ingredients for chronic musculoskeletal pain provides sufficient evidence to inform decisions for practice and self-care, specifically for Special Operations Forces personnel. METHODS: A steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. Grading of Recommendations, Assessment, Development and Evaluation was used to determine confidence in the effect estimates. The committee used a decision table to make evidence-informed judgments across decision-making factors and recommendations for practice and self-care use. RESULTS: Nineteen dietary ingredients were assessed. No recommendations were given for boswellia, ginger, rose hip, or s-adenosyl-L-methionine (SAMe); specifically, although ginger can be obtained via food, no recommendation is provided for use as a supplement due to unclear research. Further, there were insufficient strong research on boswellia and SAMe and possible compliance issues (i.e., high number of capsules required daily) associated with rose hip. CONCLUSIONS: No recommendations were made when the evidence was low quality or trade-offs were so closely balanced that any recommendation would be too speculative. Research recommendations are provided to enhance the quality and body of evidence for the most promising ingredients. Clinicians and those with chronic pain can rely on evidence-based recommendations to inform their decisions.

Dietary Ingredients as an Alternative Approach for Mitigating Chronic Musculoskeletal Pain: Evidence-Based Recommendations for Practice and Research in the Military.

OBJECTIVE: Approximately 55-76% of Service members use dietary supplements for various reasons, including pain and related outcomes. This work evaluates current research on dietary ingredients for chronic musculoskeletal pain to inform decisions for practice and self-care, specifically for Special Operations Forces personnel. METHODS: A steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. GRADE was used to determine confidence in the effect estimates. The committee made evidence-informed judgments and recommendations for practice and self-care use. RESULTS: Nineteen eligible dietary ingredients were assessed for quality, efficacy, and safety. Avocado soybean unsaponifiables, capsaicin, curcuma, ginger (as a food source), glucosamine, melatonin, polyunsaturated fatty acids, and vitamin D were conditionally recommended as their benefits outweighed risks, but there was still some uncertainty about the trade-offs. No recommendations were made for boswellia, ginger (as a dietary supplement), rose hip, or s-adenosyl-L-methionine. Recommendations were made against the use of collagen, creatine, devil's claw, l-carnitine, methylsulfonylmethane, pycnogenol, willow bark extract, and vitamin E. Research priorities were developed to address gaps precluding stronger recommendations. CONCLUSIONS: Currently the scientific evidence is insufficiently robust to establish definitive clinical practice guidelines, but processes could be established to track the impact of these ingredients. Until then, providers have the evidence needed to make informed decisions about the safe use of these dietary ingredients, and future research can address existing gaps.

The Impact of Massage Therapy on Function in Pain Populations-A Systematic Review and Meta-Analysis of Randomized Controlled Trials: Part II, Cancer Pain Populations.

PURPOSE: Pain is multi-dimensional and may be better addressed through a holistic, biopsychosocial approach. Massage therapy is commonly practiced among patients seeking pain management; however, its efficacy is unclear. This systematic review and meta-analysis is the first to rigorously assess the quality of massage therapy research and evidence for its efficacy in treating pain, function-related and health-related quality of life in cancer populations. METHODS: Key databases were searched from inception through February 2014. Eligible randomized controlled trials were assessed for methodological quality using the SIGN 50 Checklist. Meta-analysis was applied at the outcome level. A diverse steering committee interpreted the results to develop recommendations. RESULTS: Twelve high quality and four low quality studies were subsequently included in the review. Results demonstrate massage therapy is effective for treating pain compared to no treatment [standardized mean difference (SMD) = -.20] and active (SMD = -0.55) comparators. Compared to active comparators, massage therapy was also found to be beneficial for treating fatigue (SMD = -1.06) and anxiety (SMD = -1.24). CONCLUSION: Based on the evidence, weak recommendations are suggested for massage therapy, compared to an active comparator, for the treatment of pain, fatigue, and anxiety. No recommendations were suggested for massage therapy compared to no treatment or sham control based on the available literature to date. This review addresses massage therapy safety, research challenges, how to address identified research gaps, and necessary next steps for implementing massage therapy as a viable pain management option for cancer pain populations.

The Impact of Massage Therapy on Function in Pain Populations-A Systematic Review and Meta-Analysis of Randomized Controlled Trials: Part III, Surgical Pain Populations.

OBJECTIVE: Pain is multi-dimensional and may be better addressed through a holistic, biopsychosocial approach. Massage therapy is commonly practiced among patients seeking pain management; however, its efficacy is unclear. This systematic review and meta-analysis is the first to rigorously assess the quality of the evidence for massage therapy's efficacy in treating pain, function-related, and health-related quality of life outcomes in surgical pain populations. METHODS: Key databases were searched from inception through February 2014. Eligible randomized controlled trials were assessed for methodological quality using SIGN 50 Checklist. Meta-analysis was applied at the outcome level. A professionally diverse steering committee interpreted the results to develop recommendations. RESULTS: Twelve high quality and four low quality studies were included in the review. Results indicate massage therapy is effective for treating pain [standardized mean difference (SMD) = -0.79] and anxiety (SMD = -0.57) compared to active comparators. CONCLUSION: Based on the available evidence, weak recommendations are suggested for massage therapy, compared to active comparators for reducing pain intensity/severity and anxiety in patients undergoing surgical procedures. This review also discusses massage therapy safety, challenges within this research field, how to address identified research gaps, and next steps for future research.

The Impact of Massage Therapy on Function in Pain Populations-A Systematic Review and Meta-Analysis of Randomized Controlled Trials: Part I, Patients Experiencing Pain in the General Population.

PURPOSE: Pain is multi-dimensional and may be better addressed through a holistic, biopsychosocial approach. Massage therapy is commonly practiced among patients seeking pain management; however, its efficacy is unclear. This systematic review and meta-analysis is the first to rigorously assess the quality of massage therapy research and evidence for its efficacy in treating pain, function-related and health-related quality of life outcomes across all pain populations. METHODS: Key databases were searched from inception through February 2014. Eligible randomized controlled trials were assessed for methodological quality using SIGN 50 Checklist. Meta-analysis was applied at the outcome level. A diverse steering committee interpreted the results to develop recommendations. RESULTS: Sixty high quality and seven low quality studies were included in the review. Results demonstrate massage therapy effectively treats pain compared to sham [standardized mean difference (SMD) = -.44], no treatment (SMD = -1.14), and active (SMD = -0.26) comparators. Compared to active comparators, massage therapy was also beneficial for treating anxiety (SMD = -0.57) and health-related quality of life (SMD = 0.14). CONCLUSION: Based on the evidence, massage therapy, compared to no treatment, should be strongly recommended as a pain management option. Massage therapy is weakly recommended for reducing pain, compared to other sham or active comparators, and improving mood and health-related quality of life, compared to other active comparators. Massage therapy safety, research challenges, how to address identified research gaps, and necessary next steps for implementing massage therapy as a viable pain management option are discussed.

The effectiveness of melatonin for promoting healthy sleep: a rapid evidence assessment of the literature.

A systematic review was conducted using Samueli Institute's Rapid Evidence Assessment of the Literature (REAL) process to determine the evidence base for melatonin as an agent to optimize sleep or improve sleep quality, and generalize the results to a military, civilian, or other healthy, active, adult population. Multiple databases were searched yielding 35 randomized controlled trials (RCTs) meeting the review's inclusion criteria, which were assessed for methodological quality as well as for melatonin effectiveness. The majority of included studies were high quality (83.0%). Overall, according to Grading Recommendations, Assessment Development and Evaluation (GRADE) methodology, weak recommendations were made for preventing phase shifts from jet lag, for improving insomnia in both healthy volunteers and individuals with a history of insomnia, and for initiating sleep and/or improving sleep efficacy. Based on the literature to date, no recommendations for use in shift workers or to improve hormonal phase shift changes in healthy people can be made at this time. Larger and longer-duration RCTs utilizing well characterized products are needed to warrant melatonin recommendations in young, healthy adults.

Total Force Kitchen: Exploring Active-Duty Service Member Performance Optimization Through Cooking.

Introduction: Obesity, overweight, and suboptimal eating habits are threats to U.S. active-duty service member (SM) nutritional fitness. Offering programs that improve diet quality and nutritional status is of high interest to military leaders. Methods: Total force kitchen (TFK) was developed as a performance-focused multicomponent program centered around culinary skills with education and skill building in key areas of nutrition, physical activity, and mindfulness. This pilot study's objectives were to determine the feasibility and acceptability of the TFK program, to make recommendations for program modification, and to determine impact on behavior, self-efficacy, and health-related outcomes. Participants were single or geographically single active-duty SMs (n = 17) who attended the 12-week, 60-h innovative culinary education and performance optimization program at a local United Service Organization facility. A mixed-method approach assessed pre- and post-program metrics, including attrition rates and participant satisfaction. Results: The TFK program retention rate was 76.5%. All participants were "somewhat satisfied" or "very satisfied" with the overall TFK program. The highest satisfaction was with the cooking-related components. Improvements in other behavioral (d = 0.39, 95% confidence interval [CI]: -0.17 to 0.95), self-rated health (d = 0.58, 95% CI: -0.02 to 0.16), and anthropometric measures (e.g., body fat percentage: d = -0.01, 95% CI: -0.12 to 0.10) were smaller than improvements in cooking attitudes (d = 0.66, 95% CI: 0.17 to 1.13) and self-efficacy for techniques (d = 1.80, 95% CI: 0.96 to 2.62). Participants reported positive changes in lifestyle related to what they eat and how they prepare their meals. They also highly valued active learning and instructor knowledge and enthusiasm. Discussion: This multidisciplinary evidence-based program offers ample opportunities for SMs to gain knowledge, build skills, and engage in a supportive community to optimize their performance through cooking. A successful pilot has the potential to leverage resources for the TFK program expanding its reach and impact to the larger military population and nonmilitary communities.

Evidence-based telehealth interventions for posttraumatic stress disorder, depression, and anxiety: A systematic review and meta-analysis.

INTRODUCTION: The goal of this systematic review was to examine the efficacy of behavioral health care treatments for posttraumatic stress disorder (PTSD), depression, and anxiety delivered via telehealth. METHODS: We searched a combination of keywords related to telehealth, relevant mental health disorders, and evidence-based psychotherapies in three databases (PubMed, PsycInfo, and Embase) from database inception to April 2022. We included randomized controlled trials published in English wherein at least one arm received an evidence-based psychotherapy via telehealth. To be included, studies also had to enroll an adult population with symptoms or diagnosis of PTSD, depressive disorder, or anxiety disorder. RESULTS: Moderate quality of evidence was consistent with only small differences, if any, in efficacy between video teleconferencing (VTC) and in-person delivery for patients with PTSD (d = 0.06, 95% CI -0.17, 0.28). However, for those with depression, in-person delivery was associated with better outcomes compared to VTC (d = 0.28, 95% CI 0.03, 0.54; low quality of evidence). We also found that evidence-based treatments delivered over telephone were more efficacious for depression compared to treatment as usual (d = -0.47, 95% CI -0.66, -0.28; very low quality of evidence). Very low quality of evidence supported the use of telehealth versus waitlist for anxiety (d = -0.48, 95% CI -0.89, -0.09). CONCLUSIONS: A synthesis across 29 studies indicates that the efficacy of telehealth for delivery of evidence-based behavioral health interventions varies by target diagnosis and telehealth modality. More research is needed on the efficacy of telehealth treatments for depression and anxiety.

Outcomes and prognosis of adjustment disorder in adults: A systematic review.

Adjustment disorder (AD) is one of the most commonly diagnosed mental health disorders and is generally conceptualized to be mild and short-lived. Despite the frequent use of AD in clinical settings, little is known about the prognosis of this condition. Our goal was to systematically review research on a range of AD outcomes in order to provide a broad characterization of AD prognosis. We conducted searches in MEDLINE, EMBASE, and PsycINFO. We included 31 cohort or randomized controlled trials with a total of 1,385,358 participants. Many patients maintained an AD diagnosis or were diagnosed with another mental health disorder months to years after initial diagnosis. Patients with AD tended to show symptom improvement at higher rates and to utilize less treatment than did patients with other disorders. AD-diagnosed groups experienced subsequent development of numerous physical conditions, such as infection, cancers, Parkinson's disease, and cardiovascular events, at higher rates than did control groups. Results were mixed regarding suicidality and occupational impairment. We rated most studies as having a moderate risk of bias. Based on limited findings, AD appears to progress as a milder disorder than do other disorders, but it not uncommonly transitions to more severe mental health states and may predict the development of future health issues, both mental and physical. Future prospective research that conforms to prognosis study guidelines is needed to better understand the course of this common disorder.

Dietary Supplement Ingredients for Optimizing Cognitive Performance Among Healthy Adults: A Systematic Review.

Background: Dietary supplements promoted for brain health and enhanced cognitive performance are widely available. Claims made for these products are directed not only to the elderly wishing to prevent or mitigate cognitive decline, but also young healthy populations looking to boost their cognitive performance. It is unclear whether these claims made on product bottles and through advertising match the science. Objectives: To explore the evidence on the efficacy and safety of single dietary supplement ingredients frequently marketed with claims of enhanced cognitive performance among healthy adults. Design: A systematic review. Results: Nine of 54 dietary supplement ingredients identified through a scoping review met the eligibility criteria with at least 3 published studies identified per ingredient, yielding 69 unique publications. Ingredients evaluated included Bacopa monnieri, choline, creatine, omega-3 fatty acids, Ginkgo biloba, ginseng, Rhodiola rosea, tyrosine, and valerian root, all in supplement form and compared with a placebo, at various serving sizes and durations of use. Conclusions: The low level of certainty in the state of the science, coupled with not always knowing what is in a dietary supplement product, make weighing risks and benefits difficult; these data hinder the ability to develop recommendations about using such ingredients for consumers interested in boosting their cognitive performance. Whereas certain trends regarding promising serving sizes or duration for use, are pointed to in this synthesis, when combined, studies are inconsistent and imprecise, and many are methodologically flawed. Potential solutions to address research gaps are offered, for future research next steps, which is needed to strengthen the evidence and inform decisions.

Prioritized research recommendations and potential solutions: addressing gaps surrounding dietary supplement ingredients for boosting brain health and optimizing cognitive performance.

In the market of dietary supplements, a low level of certainty exists in the state of the science, coupled with not always knowing what is in the product. Together these issues make weighing benefits/risks difficult and hinder the ability to guide evidence-based practice decisions. The authors sought to identify priorities and develop potential solutions to address research gaps so that information disseminated, can ultimately, be relied upon, when trying to make appropriate and safe decisions. Using a modified-Delphi process, 8 panelists reviewed evidence, provided from systematic review, on dietary supplement ingredients for brain health, and prioritized gaps identified and offered potential solutions. Research gaps specific to dietary supplements research included the need for quality testing of products, the question of bioavailability and absorption of ingredients, and optimal composition and standardization of supplements under investigation. Other gaps related to populations studied; a general sense of bias towards focusing research on diseased rather than maintaining or optimizing performance in healthy populations. Additionally, the lack of uniform cognitive performance measures and metrics used across research is a gap, as well as whether the metrics are accurate representations of or even generalizable to "real-life" participants wishing to optimize their performance. Methodological quality and ethical concerns in the conduct and reporting of science encompass all issues. If resources map to potential solutions outlined in this paper, then these proposed next steps offered will help facilitate meaningful research, move evidence into practice recommendations, and ultimately develop better decision-making tools for consumers to trust and rely upon for making safe supplement decisions.

Analytical Challenges and Metrological Approaches to Ensuring Dietary Supplement Quality: International Perspectives.

The increased utilization of metrology resources and expanded application of its' approaches in the development of internationally agreed upon measurements can lay the basis for regulatory harmonization, support reproducible research, and advance scientific understanding, especially of dietary supplements and herbal medicines. Yet, metrology is often underappreciated and underutilized in dealing with the many challenges presented by these chemically complex preparations. This article discusses the utility of applying rigorous analytical techniques and adopting metrological principles more widely in studying dietary supplement products and ingredients, particularly medicinal plants and other botanicals. An assessment of current and emerging dietary supplement characterization methods is provided, including targeted and non-targeted techniques, as well as data analysis and evaluation approaches, with a focus on chemometrics, toxicity, dosage form performance, and data management. Quality assessment, statistical methods, and optimized methods for data management are also discussed. Case studies provide examples of applying metrological principles in thorough analytical characterization of supplement composition to clarify their health effects. A new frontier for metrology in dietary supplement science is described, including opportunities to improve methods for analysis and data management, development of relevant standards and good practices, and communication of these developments to researchers and analysts, as well as to regulatory and policy decision makers in the public and private sectors. The promotion of closer interactions between analytical, clinical, and pharmaceutical scientists who are involved in research and product development with metrologists who develop standards and methodological guidelines is critical to advance research on dietary supplement characterization and health effects.

Structural basis for tuning activity and membrane specificity of bacterial cytolysins.

Cholesterol-dependent cytolysins (CDCs) are pore-forming proteins that serve as major virulence factors for pathogenic bacteria. They target eukaryotic cells using different mechanisms, but all require the presence of cholesterol to pierce lipid bilayers. How CDCs use cholesterol to selectively lyse cells is essential for understanding virulence strategies of several pathogenic bacteria, and for repurposing CDCs to kill new cellular targets. Here we address that question by trapping an early state of pore formation for the CDC intermedilysin, bound to the human immune receptor CD59 in a nanodisc model membrane. Our cryo electron microscopy map reveals structural transitions required for oligomerization, which include the lateral movement of a key amphipathic helix. We demonstrate that the charge of this helix is crucial for tuning lytic activity of CDCs. Furthermore, we discover modifications that overcome the requirement of cholesterol for membrane rupture, which may facilitate engineering the target-cell specificity of pore-forming proteins.

A Public Health Issue: Dietary Supplements Promoted for Brain Health and Cognitive Performance.

Background: Dietary supplements targeting brain health have quickly emerged in the marketplace as cognitive performance becomes an important public health issue. While manufacturers are required to report the exact ingredients and formulations listed on the Supplement Facts labels of products, many reports have indicated such labels are not always truthful, and the content of some products is inconsistent with the ingredients listed on the Supplement Facts label. Objectives: To identify dietary supplement products and ingredients marketed for brain health and cognitive performance and perform analyses of select products to verify whether purported claims are truthful and product labels accurate. Design: A scoping review was performed to identify products and ingredients. Products were selected for content analysis, investigated for scientific-sounding claims made, and assessed using an educational tool for potential red flags when reading Supplement Facts labels. Results: Twelve products were selected from the 650 products being marketed for brain health and queried about by Service Members. Eight (67%) had at least one ingredient listed on the Supplement Facts label not detected through analysis. Compounds not reported on the label were detected in 10 (83%) products. Scientific-sounding claims made are not supported by science and red flags are presented. Conclusions: There are dietary supplements targeting brain health being marketed to consumers that should be considered adulterated and misbranded. Advertisements and product labels may be deceiving and could put the public at risk. Education is required so that the public can recognize red flags while the U.S. Food and Drug Administration works to "modernize" the current regulations for dietary supplements.

Evaluation of an Integrative Post-Traumatic Stress Disorder Treatment Program.

OBJECTIVES: Post-traumatic stress disorder (PTSD) and combat-related stress can be refractory, pervasive, and have a devastating impact on those affected, their families, and society at large. Challenges dealing with symptoms may in turn make a servicemember more susceptible to problems, including alcohol abuse, interpersonal conflict, and occupational problems. An effective treatment strategy will address multifactorial issues by using a holistic multimodal approach. Back on Track is an intensive outpatient program utilizing a holistic philosophy and multimodal treatments to provide a whole systems approach for the treatment of combat-related stress reactions and PTSD in active duty servicemembers. DESIGN/SETTING/SUBJECTS: An explanatory, sequential, mixed-methods program evaluation was conducted to assess the effectiveness of a PTSD and combat stress treatment program. Quantitative outcomes were collected and analyzed on 595 participants at pre- and postinterventions and 6-week follow-up and qualitative data were gathered through participant interviews. INTERVENTION: The manualized program uses a multimodal, psychoeducational group therapy format with a holistic approach for treating combat stress, increasing resiliency, and assisting with reintegration. Rotating providers visit from other programs and services to deliver content in bio-psycho-social-spiritual domains, including didactic lectures on mindfulness and the relaxation response and daily sessions of yoga nidra and meditation. OUTCOME MEASURES: The primary outcome measure was PTSD symptom severity assessed with the PTSD Checklist-Military Version (PCL-M). Secondary outcomes included self-efficacy, knowledge, use, and satisfaction. Quantitative data were contextualized with interview data. RESULTS: Results demonstrated a highly statistically significant effect of the program when comparing within-subject PCL-M scores before and after program participation, signed rank S (N = 595) = -47,367, p < 0.001. This translates to a moderate effect size, Cohen's d (N = 595) = -0.55, 95% confidence interval = -0.62 to -0.47, and a mean decrease of 7 points on the PCL-M at postintervention, demonstrating response to treatment. There were significant increases in knowledge and self-efficacy and high levels of satisfaction with the program overall, content, materials, and delivery. CONCLUSIONS: The treatment program has served ∼800 servicemembers since inception and has since expanded to five installations. The provision of whole systems care where the approach is holistic, multimodal, and multidisciplinary may be a way forward for the successful treatment of PTSD and other debilitating behavioral health conditions in military contexts and beyond.

Advances in cryoEM and its impact on ß-pore forming proteins.

Deployed by both hosts and pathogens, ß-pore-forming proteins (ß-PFPs) rupture membranes and lyse target cells. Soluble protein monomers oligomerize on the lipid bilayer where they undergo dramatic structural rearrangements, resulting in a transmembrane ß-barrel pore. Advances in electron cryo-microscopy (cryoEM) sample preparation, image detection, and computational algorithms have led to a number of recent structures that reveal a molecular mechanism of pore formation in atomic detail.

CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers.

The membrane attack complex (MAC) is one of the immune system's first responders. Complement proteins assemble on target membranes to form pores that lyse pathogens and impact tissue homeostasis of self-cells. How MAC disrupts the membrane barrier remains unclear. Here we use electron cryo-microscopy and flicker spectroscopy to show that MAC interacts with lipid bilayers in two distinct ways. Whereas C6 and C7 associate with the outer leaflet and reduce the energy for membrane bending, C8 and C9 traverse the bilayer increasing membrane rigidity. CryoEM reconstructions reveal plasticity of the MAC pore and demonstrate how C5b6 acts as a platform, directing assembly of a giant ß-barrel whose structure is supported by a glycan scaffold. Our work provides a structural basis for understanding how ß-pore forming proteins breach the membrane and reveals a mechanism for how MAC kills pathogens and regulates cell functions.