Serum-Derived Bovine Immunoglobulin Promotes Barrier Integrity and Lowers Inflammation for 24 Human Adults Ex Vivo.

Serum-derived bovine immunoglobulin (SBI) prevents translocation and inflammation via direct binding of microbial components. Recently, SBI also displayed potential benefits through gut microbiome modulation. To confirm and expand upon these preliminary findings, SBI digestion and colonic fermentation were investigated using the clinically predictive ex vivo SIFR® technology (for 24 human adults) that was, for the first time, combined with host cells (epithelial/immune (Caco-2/THP-1) cells). SBI (human equivalent dose (HED) = 2 and 5 g/day) and the reference prebiotic inulin (IN; HED = 2 g/day) significantly promoted gut barrier integrity and did so more profoundly than a dietary protein (DP), especially upon LPS-induced inflammation. SBI also specifically lowered inflammatory markers (TNF-α and CXCL10). SBI and IN both enhanced SCFA (acetate/propionate/butyrate) via specific gut microbes, while SBI specifically stimulated valerate/bCFA and indole-3-propionic acid (health-promoting tryptophan metabolite). Finally, owing to the high-powered cohort (n = 24), treatment effects could be stratified based on initial microbiota composition: IN exclusively stimulated (acetate/non-gas producing) Bifidobacteriaceae for subjects classifying as Bacteroides/Firmicutes-enterotype donors, coinciding with high acetate/low gas production and thus likely better tolerability of IN. Altogether, this study strongly suggests gut microbiome modulation as a mechanism by which SBI promotes health. Moreover, the SIFR® technology was shown to be a powerful tool to stratify treatment responses and support future personalized nutrition approaches.

The smallest functional antibody fragment: Ultralong CDR H3 antibody knob regions potently neutralize SARS-CoV-2.

Cows produce antibodies with a disulfide-bonded antigen-binding domain embedded within ultralong heavy chain third complementarity determining regions. This "knob" domain is analogous to natural cysteine-rich peptides such as knottins in that it is small and stable but can accommodate diverse loops and disulfide bonding patterns. We immunized cattle with SARS-CoV-2 spike and found ultralong CDR H3 antibodies that could neutralize several viral variants at picomolar IC50 potencies in vitro and could protect from disease in vivo. The independent CDR H3 peptide knobs were expressed and maintained the properties of the parent antibodies. The knob interaction with SARS-CoV-2 spike was revealed by electron microscopy, X-ray crystallography, NMR spectroscopy, and mass spectrometry and established ultralong CDR H3-derived knobs as the smallest known recombinant independent antigen-binding fragment. Unlike other vertebrate antibody fragments, these knobs are not reliant on the immunoglobulin domain and have potential as a new class of therapeutics.

Associations of health care staff burnout with negative health and organizational outcomes in the U.S. military health system.

RATIONALE: Burnout is a personal and occupational phenomenon that has been associated with negative physical and psychological outcomes in medical staff. Additionally, there are implications for healthcare organizations, as those staff who are burned out are more likely to have lower productivity or leave the organization. As with the Covid-19 pandemic, future national emergencies and potentially large-scale conflicts will require similar and likely even larger scale responses from the U.S. Military Health System, thus it is important to understand burnout in this population so that the readiness of the staff and the military can remain at a high level. OBJECTIVE: This assessment was designed to examine levels of burnout among United States Military Health System (MHS) staff working at Army installations and the factors that influence the development of burnout. METHODS: Anonymous data was collected from 13,558 active-duty U.S. Soldiers and civilian MHS employees. Burnout was measured using the Copenhagen Burnout Inventory and the Mini-Z. RESULTS: Results showed nearly half of staff who responded (48%) reported being burned out, an increase since last measured in 2019 (31%). Factors related to increased burnout included concerns about work/life balance and workload, low job satisfaction and feeling disconnected from others. Burnout was associated with increases in adverse physical and behavioral health (BH) outcomes. CONCLUSIONS: Results indicate that burnout is a common problem across MHS Army staff and is related to significant adverse health consequences for the individual and reduced retention of staff for the organization. These findings highlight the need to address burnout through policies that standardize health care delivery policies and practices, providing support to leadership to promote a healthy workplace, and individual support to those who experience burnout.

Serum-Derived Bovine Immunoglobulin Stimulates SCFA Production by Specific Microbes in the Ex Vivo SIFR® Technology.

Serum-derived bovine immunoglobulins (SBI) exert health benefits mediated by their ability to bind microbial components, thereby preventing translocation and subsequent inflammation. While in vivo studies have shown that a fraction of SBI also reaches the colon, little is known about the impact of SBI on the dense colonic microbiota that has great potential to impact human health. This study, therefore, investigated the impact of three bovine plasma protein fractions (SBI, bovine plasma (BP) and albumin-enriched bovine plasma (ABP)) on the gut microbiota of six human adults using the novel ex vivo SIFR® technology, recently demonstrated to generate predictive findings for clinical studies. When dosed at an equivalent of 5 g/day, all protein fractions significantly increased health-related metabolites-acetate, propionate, and butyrate. Upon simulating small intestinal absorption, SBI still markedly increased acetate and propionate, demonstrating that SBI is more resistant to small intestinal digestion and absorption compared to the other protein sources. Despite noticeable interindividual differences in microbiota composition among human adults, SBI consistently stimulated a narrow spectrum of gut microbes, which largely differed from the ones that are typically involved in carbohydrate fermentation. The SBI-fermenting consortium included B. vulgatus and L. edouardi (correlating with acetate and propionate) along with Dorea longicatena, Coprococcus comes and the butyrate-producing bacterium SS3/4 (correlating with butyrate). Overall, this study revealed that protein bovine fractions can contribute to health benefits by specifically modulating the human gut microbiota. While health benefits could follow from the production of SCFA, a broader range of protein-derived metabolites could also be produced. This study also confirms that the concept of prebiotics (substrates selectively utilized by host microorganisms conferring a health benefit) could go beyond the use of ingestible carbohydrates and extend to partially indigestible proteins.

Potential use of serum-derived bovine immunoglobulin/protein isolate for the management of COVID-19.

COVID-19 manifests as a mild disease in most people but can progress to severe disease in nearly 20% of individuals. Disease progression is likely driven by a cytokine storm, either directly stimulated by SARS-CoV-2 or by increased systemic inflammation in which the gut might play an integral role. SARS-CoV-2 replication in the gut may cause increased intestinal permeability, alterations to the fecal microbiome, and increased inflammatory cytokines. Each effect may lead to increased systemic inflammation and the transport of cytokines and inflammatory antigens from the gut to the lung. Few interventions are being studied to treat people with mild disease and prevent the cytokine storm. Serumderived bovine immunoglobulin/protein isolate (SBI) may prevent progression by (1) binding and neutralizing inflammatory antigens, (2) decreasing gut permeability, (3) interfering with ACE2 binding by viral proteins, and (4) improving the fecal microbiome. SBI is therefore a promising intervention to prevent disease progression in COVID-19 patients.

Intrafraction motion during frameless radiosurgery using Varian HyperArcTM and BrainLab ElementsTM immobilization systems.

Commercial systems such as Varian HyperArcTM and BrainLab Elements MultiMetTM have been developed that allow radiosurgery treatment of multiple brain metastases using a single isocenter. Each software package places increased demands on frameless immobilization and requires the use of a specific immobilization system: the QFix-Encompass system for Varian and the BrainLab frameless-mask system for BrainLab. At our institution, patients receiving traditional radiosurgery (one isocenter per target lesion) were treated using both immobilization systems. Intrafraction motion was determined for each patient using multiple cone-beam CT scans and the same image-registration software during treatment. There were no statistically-significant differences in mean absolute translational shifts between the two mask systems, with a mean 3D-vector motion of approximately 0.43 mm for both systems. There were also no statistically-significant differences in the mean absolute rotational shifts between the two mask systems. Although the average residual errors were insignificant between the mask systems, special attention should be paid to individual maximum shifts with both systems. Large maximum rotational misalignments could present significant misalignment of lesions as distance increases from the isocenter. Finally, large maximum shifts highlight the need for real-time monitoring of patient movement during radiosurgery of multiple lesions using a single isocenter.

Effect of Cellulose Nanofibrils and TEMPO-mediated Oxidized Cellulose Nanofibrils on the Physical and Mechanical Properties of Poly(vinylidene fluoride)/Cellulose Nanofibril Composites.

Cellulose nanofibrils (CNFs) are high aspect ratio, natural nanomaterials with high mechanical strength-to-weight ratio and promising reinforcing dopants in polymer nanocomposites. In this study, we used CNFs and oxidized CNFs (TOCNFs), prepared by a 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation process, as reinforcing agents in poly(vinylidene fluoride) (PVDF). Using high-shear mixing and doctor blade casting, we prepared free-standing composite films loaded with up to 5 wt % cellulose nanofibrils. For our processing conditions, all CNF/PVDF and TOCNF/PVDF films remain in the same crystalline phase as neat PVDF. In the as-prepared composites, the addition of CNFs on average increases crystallinity, whereas TOCNFs reduces it. Further, addition of CNFs and TOCNFs influences properties such as surface wettability, as well as thermal and mechanical behaviors of the composites. When compared to neat PVDF, the thermal stability of the composites is reduced. With regards to bulk mechanical properties, addition of CNFs or TOCNFs, generally reduces the tensile properties of the composites. However, a small increase (~18%) in the tensile modulus was observed for the 1 wt % TOCNF/PVDF composite. Surface mechanical properties, obtained from nanoindentation, show that the composites have enhanced performance. For the 5 wt % CNF/PVDF composite, the reduced modulus and hardness increased by ~52% and ~22%, whereas for the 3 wt % TOCNF/PVDF sample, the increase was ~23% and ~25% respectively.

Maximizing the Division Psychiatrist's Garrison Prevention Role to Meet the U.S. Army's 21st Century Readiness Expectations.

INTRODUCTION: The division psychiatrist has been a bedrock U.S. Army institution for nearly 100 years. The role of the position in combat is well established, but its role in garrison has historically been less well defined. Prevention of behavioral health casualties has long been a governing objective of the division psychiatrist and forms the cornerstone of the behavioral health (BH) readiness concept. Accordingly, the Army's increased emphasis on readiness mandates that the division psychiatrist maximize BH force readiness through applied prevention methods. This process begins in garrison, and the crucible of recent protracted conflict has yielded effective BH screening principles applied in that environment. Despite this achievement, an evolving operational environment threatens the blanket effectiveness of BH screening and prevention in garrison. This article examines the historical evolution of the division psychiatrist's role in garrison, elucidates division psychiatry BH readiness principles in garrison, and expands on previously documented division psychiatry led efforts to maximize BH readiness levels. MATERIALS AND METHODS: A historical review of the division psychiatrist was conducted in order to analyze the role of the position in BH prevention operations. Identified division psychiatry preventive lessons are leveraged against current BH readiness challenges resulting in proposed solutions from a division psychiatry perspective. RESULTS: The historical trajectory of the division psychiatrist's role in garrison prevention operations has advanced significantly in the last 17 years. With the advent of evidence-based BH readiness findings, the division psychiatrist's garrison readiness duties have expanded to include analysis of unit BH readiness levels. By applying pre-deployment screening principles in new ways to existing BH readiness platforms, the division psychiatrist can analyze BH readiness levels much earlier than immediately prior to deployment. The resultant BH readiness feedback allows for individualized readiness improvements for the BH systems that serve Army units. The division psychiatrist is the natural proponent of such readiness efforts, and will require staff officer, consultant, liaison, and trainer skill sets in order to be successful. CONCLUSIONS: The division psychiatrist's role must adapt to a changing operational environment in order to preserve and build on historical successes. The recommended end state would see the division psychiatrist maintaining a robust pre/post-deployment BH screening process and organizing the regular analysis of BH readiness levels to optimize existing BH clinical platforms. Systematically pursued, this would not only maximize BH readiness, but dramatically enhance safety and the provision of resources towards soldier health and welfare across the Army. The division psychiatrist should lead this effort.

Co-evolution of physical and social sciences in synthetic biology.

Emerging technologies research often covers various perspectives in disciplines and research areas ranging from hard sciences, engineering, policymaking, and sociology. However, the interrelationship between these different disciplinary domains, particularly the physical and social sciences, often occurs many years after a technology has matured and moved towards commercialization. Synthetic biology may serve an exception to this idea, where, since 2000, the physical and the social sciences communities have increasingly framed their research in response to various perspectives in biological engineering, risk assessment needs, governance challenges, and the social implications that the technology may incur. This paper reviews a broad collection of synthetic biology literature from 2000-2016, and demonstrates how the co-development of physical and social science communities has grown throughout synthetic biology's earliest stages of development. Further, this paper indicates that future co-development of synthetic biology scholarship will assist with significant challenges of the technology's risk assessment, governance, and public engagement needs, where an interdisciplinary approach is necessary to foster sustainable, risk-informed, and societally beneficial technological advances moving forward.

Trends in Synthetic Biology Applications, Tools, Industry, and Oversight and Their Security Implications.

Recent developments in synthetic biology tools and techniques are driving commercialization of a wide range of products for human health, agriculture, environmental stewardship, and other purposes. This article reviews some of the trends in synthetic biology applications as well as some of the tools enabling these and future advances. These tools and capabilities are being developed in the context of a rapidly changing industry, which may have an impact on the rate and direction of progress. Final products are subject to a regulatory framework that is being challenged by the pace, scale, and novelty of this new era of biotechnology. This article includes discussion of these factors and how they may affect product design and the types of applications that are most likely to be supported and pursued commercially. The final section provides perspective on the security implications of these advances, with a focus on US interests.

Review of Vertebral Augmentation: An Updated Meta-analysis of the Effectiveness.

BACKGROUND: To update vertebral augmentation literature by comparing outcomes between vertebroplasty (VP), balloon kyphoplasty (BKP), vertebral augmentation with implant (VAI), and nonsurgical management (NSM) for treating vertebral compression fractures (VCFs). METHODS: A PubMed literature search was conducted with keywords kyphoplasty, vertebroplasty, vertebral body stent, and vertebral augmentation AND implant for English-language articles from February 1, 2011, to November 22, 2016. Among the results, 25 met the inclusion criteria for the meta-analysis. Inclusion criteria were prospective comparative studies for mid-/lower-thoracic and lumbar VCFs enrolling at least 20 patients. Exclusion criteria included studies that were single arm, systematic reviews and meta-analyses, traumatic nonosteoporotic or cancer-related fractures, lack of clinical outcomes, or non-Level I and non-Level II studies. Standardized mean difference between baseline and end point for each outcome was calculated, and treatment groups were pooled using random effects meta-analysis. RESULTS: Visual analog scale pain reduction for BKP and VP was -4.05 and -3.88, respectively. VP was better than but not significantly different from NSM (-2.66), yet BKP showed significant improvement from both NSM and VAI (-2.77). The Oswestry Disability Index reduction for BKP showed a significant improvement over VAI (P < .001). There was no significant difference in changes between BKP and VP for anterior (P = .226) and posterior (P = .293) vertebral height restoration. There was no significant difference in subsequent fractures following BKP (32.7%; 95% confidence interval [CI]: 8.8%-56.6%) or VP (28.3%; 95% CI: 7.0%-49.7%) compared with NSM (15.9%; 95% CI: 5.2%-26.6%). CONCLUSIONS/LEVEL OF EVIDENCE: Based on Level I and II studies, BKP had significantly better and VP tended to have better pain reduction compared with NSM. BKP tended to have better height restoration than VP. Additionally, BKP had significant improvements in pain reduction and disability score as compared with VAI. CLINICAL RELEVANCE: This meta-analysis serves to further define and support the safety and efficacy of vertebral augmentation.

The Bioactive Lipid (S)-Sebastenoic Acid Impacts Motility and Dispersion in Vibrio cholerae.

Although Gram-negative bacterial pathogens continue to impart a substantial burden on global healthcare systems, much remains to be understood about aspects of basic physiology in these organisms. In recent years, cyclic-diguanylate (c-di-GMP) has emerged as a key regulator of a number of important processes related to pathogenicity, including biofilm formation, motility and virulence. In an effort to discover chemical genetic probes for studying V. cholerae we have developed a new motility-based high-throughput screen to identify compounds that modulate c-di-GMP levels. Using this new screening platform, we tested a library of microbially-derived marine natural products extracts, leading to the discovery of the bioactive lipid (S)-sebastenoic acid. Evaluation of the effect of this new compound on bacterial motility, vpsL expression and biofilm formation implied that (S)-sebastenoic acid may alter phenotypes associated to c-di-GMP signaling in V. cholerae.

Sacroplasty: A Ten-Year Analysis of Prospective Patients Treated with Percutaneous Sacroplasty: Literature Review and Technical Considerations.

BACKGROUND: The treatment of sacral fractures has evolved since its first description in 1982. Several techniques for sacral augmentation have been developed since 2001, and the rate of improvement is rapid with over 50% reduction in pain achieved prior to post-procedure discharge of the patient. Pain reduction occurs primarily within the first 3 months and is sustained at 12 months; however, the long-term outcomes have not previously been studied. OBJECTIVES: We aim to evaluate the long-term efficacy of sacroplasty versus non-surgical management (NSM) in treating sacral insufficiency fractures (SIFs), including the effect on pain relief, opioid and other analgesic use, patient satisfaction, and complication rates. Additionally, we aim to review the most current sacroplasty literature. STUDY DESIGN: A 10-year prospective, observational cohort study of patients with SIFs treated with sacral augmentation. SETTING: A single-center interventional pain management private practice. METHODS: Two-hundred and forty-four patients with SIFs were treated with sacroplasty (210 patients) or NSM (34 patients) beginning in January 2004 and then followed for 10 years. The patients' gender, age, pre-procedure pain duration, analgesic use, pain level, and satisfaction were recorded at baseline and at post-procedure follow-up intervals of 2, 4, 12, 24, 52 weeks, and 2 years. The experimental group was then contacted at 10 years. Post-procedure complications before discharge and at each follow-up were also evaluated. RESULTS: Both NSM and sacroplasty resulted in statistically significant drops in visual analog scale (VAS) scores from pre-treatment to 2-year follow-up (P < 0.001). When measured from follow-up to follow-up, the NSM group's only significant decrease in the mean VAS score was between pre-treatment and 2 weeks (P = 0.002). The experimental group had significant decreases over the periods pre-op through post-op (P < 0.001), post-op through 2 weeks (P < 0.001), 12 weeks through 24 weeks (P = 0.014), and 24 weeks through one year (P = 0.002). The experimental cohort experienced statistically significant drops in the mean VAS scores between follow-ups for a longer period of time. Opioid and non-opioid analgesic use was markedly decreased preoperatively to postoperatively and was sustained at the 10-year follow-up. LIMITATIONS: Patients were placed into the control group, NSM, if they did not meet inclusion criteria for sacroplasty. However, the baseline characteristics of the sacroplasty versus NSM group were not statistically different. Additionally, the control group was only followed through 2 years and was not contacted at the 10-year follow-up. CONCLUSIONS: Our results and those reported in previous studies establish that sacroplasty allows for decreased use of medications and results in pain relief, greater patient mobility, and improved patient satisfaction. In addition to the published body of literature, our results show strong evidence in support of sacroplasty as a safe and efficacious treatment of SIFs. KEY WORDS: Sacroplasty, sacral fracture, fracture, osteoporosis, insufficiency, radiology.

Analysis of Reporting Bias in Vertebral Augmentation.

Osteoporotic vertebral compression fractures (OVCFs) are a significant cause of morbidity and mortality in the United States and worldwide, with estimates of 750,000 to 1.5 million occurring annually. As the elderly population continues to increase, the incidence of OVCFs will continue to rise, as will the morbidity and mortality associated with this condition. Vertebral augmentation (VA) was almost universally accepted as the appropriate treatment modality prior to 2 sham trials published in 2009 by the New England Journal of Medicine (NEJM). Subsequently, there is now significant controversy regarding the optimal treatment of OVCFs. Since 2009 there have been 6 prospective randomized controlled studies (PRCTs) and 2 meta-analyses on VA for the treatment of OVCFs. Five of the PRCTs and both of the meta-analyses have shown superior results with VA as compared with nonsurgical management (NSM). However, a recent health technology assessment and review article continue to over-emphasize the 2 NEJM sham trials, despite the most current literature. These are examples of inconsistent or biased data reporting with overemphasis on certain trial types and exclusion of other types of data, resulting in the reporting of conclusions that are partially representative or not representative of the complete data. As clinical investigators, we have a responsibility to limit bias and ensure that the appropriate treatment modalities are made available to vulnerable populations.The aim of this perspective analysis is to examine sources of bias in reporting and some of the publications that contain it, along with comparing the publications to the current body of published literature relevant to this topic. KEY WORDS: Vertebral augmentation, vertebroplasty, kyphoplasty, bias, osteoporosis, compression fracture.

Serious Adverse Events Associated with Readmission Through One Year After Vertebral Augmentation with Either a Polyetheretherketone Implant or Balloon Kyphoplasty.

BACKGROUND: The KAST (Kiva Safety and Efficacy) investigation device exempt (IDE) study indicated that the majority of patients responded equally well to vertebral augmentation using either an implant-based approach or balloon kyphoplasty (BK). Additional investigation has suggested that a subset of patients may benefit further by avoiding repeated readmissions due to serious adverse events (SAEs) if they receive one vertebral augmentation approach over another. OBJECTIVES: The primary aim was to assess the effect of 2 different augmentation procedures on readmission rates for SAEs. STUDY DESIGN: The KAST trial is a pivotal, multicenter, randomized, controlled trial conducted to evaluate an implant-based vertebral augmentation approach (implant) against BK. Post-hoc analysis was performed to evaluate SAEs and readmission rates. SETTING: Twenty-one sites in North America and Europe. METHODS: The treatment effect of vertebral implant versus BK on SAEs requiring unplanned readmission was evaluated by estimating the risk of SAEs associated with readmissions in KAST while controlling for key baseline covariates using multivariate Poisson regression modeling. RESULTS: Forty (27.8%) patients with implants had 69 SAEs associated with readmission compared to 44 (31.2%) patients with BK having 103 events. The risk for all SAEs leading to readmission was 34.4% lower with the implant than for BK (95% confidence interval = 11.1%, 51.7%; P < 0.01). Multivariate analysis showed that the risk of SAEs associated with readmission was decreased in subjects treated with the implant compared to BK, and increased in patients with prior histories of vertebral compression fractures (VCFs) or significant osteoporosis. LIMITATIONS: The power of the KIVA study was based on clinical efficacy criteria to meet FDA requirements and recommendations for equivalency or noninferiority. The primary endpoint in this post-hoc analysis is SAEs associated with readmissions; as a result, the sample size is underpowered, although the results remain significant. CONCLUSION: The augmentation approaches compared here have similar pain relief and quality of life effects; the implant showed a lower risk of readmissions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01123512. Key words: Vertebral compression fracture, kiva implant, balloon kyphoplasty, vertebroplasty, health economics, osteoporosis.

Production of tunable nanomaterials using hierarchically assembled bacteriophages.

Large-scale fabrication of precisely defined nanostructures with tunable functions is critical to the exploitation of nanoscience and nanotechnology for production of electronic devices, energy generators, biosensors, and bionanomedicines. Although self-assembly processes have been developed to exploit biological molecules for functional materials, the resulting nanostructures and functions are still very limited, and scalable synthesis is far from being realized. Recently, we have established a bacteriophage-based biomimetic process, called 'self-templating assembly'. We used bacteriophage as a nanofiber model system to exploit its liquid crystalline structure for the creation of diverse hierarchically organized structures. We have also demonstrated that genetic modification of functional peptides of bacteriophage results in structures that can be used as soft and hard tissue-regenerating materials, biosensors, and energy-generating materials. Here, we describe a comprehensive protocol to perform genetic engineering of phage, liter-scale amplification, purification, and self-templating assembly, and suggest approaches for characterizing hierarchical phage nanostructures using optical microscopy, atomic-force microscopy (AFM), and scanning electron microscopy (SEM). We also discuss sources of contamination, common mistakes during the fabrication process, and quality-control measures to ensure reproducible material production. The protocol takes ∼8-10 d to complete.

Improving Awareness of Behavioral Health Readiness.

INTRODUCTION: Readiness for worldwide deployments as force structure decreases is of vital importance to our military. Advances in access and efforts to decrease stigma for behavioral health (BH) treatment has impacted unit readiness levels. However, concern exists that there are still a significant number of service members with behavioral health conditions who are unable to deploy. This article outlines the current state of behavioral health readiness in one U.S. Army Division and provides a programmatic review of a systems based initiative, the Behavioral Health Readiness Tool (BHRT), designed to enhance awareness of current levels. METHODS: BHRT was constructed in August 2015 and implemented in September 2015 by Unit Behavioral Health Officers. Current duty limitation profiles were reconciled with behavioral health utilization and pharmacy prescription data. Results were recorded for four enduring brigade combat teams over 7 months and reported to senior leadership on a monthly basis. A program review was conducted in April 2016 to determine whether the desired effect was occurring. RESULTS: An approximate 1% of the Division's population (100 per 10,000 soldiers) with a nondeployable behavioral health condition was found to be lacking documentation (profile) of the condition. If substance abuse was included, the total increased to a conservative estimate of 1.5%. On the basis of a limited pharmacologic review alone, an additional 2% to 3% of Division soldiers with minor behavioral conditions were also lacking a profile. CONCLUSIONS: The BHRT initiative was successful at improving behavioral health readiness by improving the documentation of nondeployable behavioral health conditions, fostering communication between parallel behavioral health services, increasing the visibility of Commanders to at-risk soldiers, and enhancing Commanders' abilities to provide for the health and welfare of their soldiers.

Suppression of Oligomer Formation and Formation of Non-Toxic Fibrils upon Addition of Mirror-Image Aß42 to the Natural l-Enantiomer.

Racemates often have lower solubility than enantiopure compounds, and the mixing of enantiomers can enhance the aggregation propensity of peptides. Amyloid beta (Aß) 42 is an aggregation-prone peptide that is believed to play a key role in Alzheimer's disease. Soluble Aß42 aggregation intermediates (oligomers) have emerged as being particularly neurotoxic. We hypothesized that the addition of mirror-image d-Aß42 should reduce the concentration of toxic oligomers formed from natural l-Aß42. We synthesized l- and D-Aß42 and found their equimolar mixing to lead to accelerated fibril formation. Confocal microscopy with fluorescently labeled analogues of the enantiomers showed their colocalization in racemic fibrils. Owing to the enhanced fibril formation propensity, racemic Aß42 was less prone to form soluble oligomers. This resulted in the protection of cells from the toxicity of l-Aß42 at concentrations up to 50 µm. The mixing of Aß42 enantiomers thus accelerates the formation of non-toxic fibrils.

A Tailored HPLC Purification Protocol That Yields High-purity Amyloid Beta 42 and Amyloid Beta 40 Peptides, Capable of Oligomer Formation.

Amyloidogenic peptides such as the Alzheimer's disease-implicated Amyloid beta (Aß), can present a significant challenge when trying to obtain high purity material. Here we present a tailored HPLC purification protocol to produce high-purity amyloid beta 42 (Aß42) and amyloid beta 40 (Aß40) peptides. We have found that the combination of commercially available hydrophobic poly(styrene/divinylbenzene) stationary phase, polymer laboratory reverse phase - styrenedivinylbenzene (PLRP-S) under high pH conditions, enables the attainment of high purity (>95%) Aß42 in a single chromatographic run. The purification is highly reproducible and can be amended to both semi-preparative and analytical conditions depending upon the amount of material wished to be purified. The protocol can also be applied to the Aß40 peptide with identical success and without the need to alter the method.

A study of radiological features of healing in long bone fractures among infants less than a year.

PURPOSE: To create a timetable for dating long bone fractures in infants aged less than 1 year using previously defined radiographic signs of fracture healing. MATERIALS AND METHODS: A retrospective cross-sectional time series of long bone fractures in infants aged less than 1 year was conducted from 2006 to 2013. After exclusion criteria were applied 59 digital image series were available for review from 40 infants. Utilizing published criteria for dating fractures, the presence or absence of four pre-defined features of healing was scored: periosteal reaction, callus, bridging, and remodeling. Three radiologists independently scored radiographs with a 3-point scale, marking each feature as present, absent, or equivocal. The times in days when features were first seen, peaked (feature agreed present in >40% of images), and last seen were noted. Statistical analysis using free marginal kappa was conducted. RESULTS: The level of agreement among the three radiologists was high (0.64-0.85). The sequence in which the features were seen was: periosteal reaction range 7-130 (present in the majority of cases between 9 and 49 days); callus range 9-130 (present in the majority of cases between days 9-26); bridging range 15-130 (seen in the majority of cases between 15 and 67 days); remodeling range 51-247 days. CONCLUSION: This study provides a timetable of radiological features of long bone healing among young infants for the first time. Dating of incomplete long bone fractures is challenging, beyond the presence of periosteal reaction, but a consistent sequence of changes is present in complete fractures.