Discovery of treatment for nerve agents targeting a new metabolic pathway.

The inhibition of acetylcholinesterase is regarded as the primary toxic mechanism of action for chemical warfare agents. Recently, there have been numerous reports suggesting that metabolic processes could significantly contribute to toxicity. As such, we applied a multi-omics pipeline to generate a detailed cascade of molecular events temporally occurring in guinea pigs exposed to VX. Proteomic and metabolomic profiling resulted in the identification of several enzymes and metabolic precursors involved in glycolysis and the TCA cycle. All lines of experimental evidence indicated that there was a blockade of the TCA cycle at isocitrate dehydrogenase 2, which converts isocitrate to α-ketoglutarate. Using a primary beating cardiomyocyte cell model, we were able to determine that the supplementation of α-ketoglutarate subsequently rescued cells from the acute effects of VX poisoning. This study highlights the broad impacts that VX has and how understanding these mechanisms could result in new therapeutics such as α-ketoglutarate.

Pain Management Best Practices from Multispecialty Organizations During the COVID-19 Pandemic and Public Health Crises.

BACKGROUND: It is nearly impossible to overestimate the burden of chronic pain, which is associated with enormous personal and socioeconomic costs. Chronic pain is the leading cause of disability in the world, is associated with multiple psychiatric comorbidities, and has been causally linked to the opioid crisis. Access to pain treatment has been called a fundamental human right by numerous organizations. The current COVID-19 pandemic has strained medical resources, creating a dilemma for physicians charged with the responsibility to limit spread of the contagion and to treat the patients they are entrusted to care for. METHODS: To address these issues, an expert panel was convened that included pain management experts from the military, Veterans Health Administration, and academia. Endorsement from stakeholder societies was sought upon completion of the document within a one-week period. RESULTS: In these guidelines, we provide a framework for pain practitioners and institutions to balance the often-conflicting goals of risk mitigation for health care providers, risk mitigation for patients, conservation of resources, and access to pain management services. Specific issues discussed include general and intervention-specific risk mitigation, patient flow issues and staffing plans, telemedicine options, triaging recommendations, strategies to reduce psychological sequelae in health care providers, and resource utilization. CONCLUSIONS: The COVID-19 public health crisis has strained health care systems, creating a conundrum for patients, pain medicine practitioners, hospital leaders, and regulatory officials. Although this document provides a framework for pain management services, systems-wide and individual decisions must take into account clinical considerations, regional health conditions, government and hospital directives, resource availability, and the welfare of health care providers.

Association Between Dietary Supplement Use and ICD-9-CM Code Classification in Active Duty US Navy and Marine Corps Service Members.

INTRODUCTION: This study is the first to our knowledge to examine associations of survey-reported dietary supplement use with medical record diagnoses, rather than retrospective self-reported supplement use at the time of the medical encounter or case reports of adverse events. Dietary supplement (DS) use and adverse events associations in US Navy and Marine Corps personnel remains unknown. This study assessed associations of DS use in active duty (AD) personnel with ICD-9-CM diagnostic codes from outpatient medical encounters from the Military Health System Data Repository (MDR). MATERIALS AND METHODS: This cross-sectional investigation used a one-time survey of DS use among AD conducted August through December 2014. Survey data were matched to MDR data accessed in September 2016, and associations between the survey responses and diagnoses were analyzed. Statistical significance was set at alpha level 0.005, and 99.5% confidence intervals (CIs) were calculated. MDR data were matched with survey results for 1,708 personnel. Multivariable logistic regression analyses examined whether use of specific classes of supplements was associated with disease. RESULTS: Results revealed significant associations between vitamin supplement use and ICD-9-CM-diagnosed diseases of the nervous system (odds ratio [OR]: 1.72, 99.5% CI: 1.11-2.68) and diseases of the musculoskeletal system and connective tissue (OR: 1.59, 99.5% CI: 1.17-2.17). Joint health supplement category use was associated with diseases of the musculoskeletal system and connective tissue (OR: 1.81, 99.5% CI: 1.12-2.94) and injury and poisoning (OR: 1.82, 99.5% CI: 1.10-3.04). CONCLUSIONS: The percentages of service members with diseases in specific ICD-9-CM diagnostic categories were similar to those reported in other studies using military medical data. There is a greater prevalence of dietary supplement use by the service members who participated in this survey compared with the general population, with 73% of US Navy and Marine Corps personnel reporting use of dietary supplements one or more times per week compared to the estimated 50% of all Americans currently using some form of dietary supplement. The DoD ensures the optimal readiness, performance, and health of its military service members, thus future longitudinal evaluation of dietary supplement use by this population will test the preliminary findings of this study.

Perceptions of Adjunctive Mindfulness-Based Cognitive Therapy to Prevent Suicidal Behavior Among High Suicide-Risk Outpatient Participants.

BACKGROUND: Few investigations of patient perceptions of suicide prevention interventions exist, limiting our understanding of the processes and components of treatment that may be engaging and effective for high suicide-risk patients. AIMS: Building on promising quantitative data that showed that adjunct mindfulness-based cognitive therapy to prevent suicidal behavior (MBCT-S) reduced suicidal thinking and depression among high suicide-risk patients, we subjected MBCT-S to qualitative inspection by patient participants. METHOD: Data were provided by 15 patients who completed MBCT-S during a focus group and/or via a survey. Qualitative data were coded using thematic analysis. Themes were summarized using descriptive analysis. RESULTS: Most patients viewed the intervention as acceptable and feasible. Patients attributed MBCT-S treatment engagement and clinical improvement to improved emotion regulation. A minority of patients indicated that factors related to the group treatment modality were helpful. A small percentage of patients found that aspects of the treatment increased emotional distress and triggered suicidal thinking. These experiences, however, were described as fleeting and were not linked to suicidal behavior. LIMITATIONS: The sample size was small. CONCLUSION: Information gathered from this study may assist in refining MBCT-S and treatments to prevent suicidal behavior among high suicide-risk patients generally.

CHARACTERIZING THE 25-HYDROXYVITAMIN D STATUS OF TWO POPULATIONS OF FREE-RANGING EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA).

Ultraviolet B radiation is recommended for captive reptiles to stimulate production of adequate levels of vitamin D; however, little is known regarding the vitamin D status in many free-ranging populations. Current reference ranges for vitamin D in eastern box turtles have not yet been established. Sixty free-ranging eastern box turtles (Terrapene carolina carolina) from two well-studied populations in Illinois (n = 24) and Tennessee (n = 36) were assayed for plasma vitamin D concentration in 2014. There were no significant differences in concentrations between individuals in Illinois (mean: 117.5 nM/L) and Tennessee (mean: 98.7 nM/L) (P = 0.129) populations. Similarly, there were no differences in concentrations based on age class (P = 0.533) or sex (P = 0.532). There was a significant correlation between UV at the time of capture and vitamin D concentrations (R = 0.301, P = 0.030). Vitamin D was not correlated with total calcium (R = 0.018, P = 0.89) or Ca : P ratio (R = 0.025, P = 0.85). Diseases in captive individuals, including secondary nutritional hyperparathyroidism, may commonly be associated with vitamin D deficiencies, and clinical intervention relies on reference data. Vitamin D supplementation may be recommended if animals are deemed to be deficient. Data obtained can be used to improve the care of captive and free-ranging turtles by providing reference ranges, as well as better characterize the health of wild populations.

Purified umbilical cord derived mesenchymal stem cell treatment in a case of systemic lupus erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a multiple organ system autoimmune disorder for which there is no known cure. METHODS: We report a case of a young adult lady with SLE and Sjogren's with diagnostic and clinical resolution following purified umbilical cord derived mesenchymal stem cell (MSC) and globulin component protein macrophage activating factor (GcMAF) therapy in a combined multidisciplinary integrative medicine protocol. RESULTS: Our patient had complete reversal of all clinical and laboratory markers. CONCLUSION: We recommend a prospective randomized double blind study to assess the sustained efficacy of MSC and GcMAF in the treatment of autoimmune connective tissue diseases such as systemic lupus erythematosus.

Improvements in Executive Attention, Rumination, Cognitive Reactivity, and Mindfulness Among High-Suicide Risk Patients Participating in Adjunct Mindfulness-Based Cognitive Therapy: Preliminary Findings.

OBJECTIVE: To test changes to cognitive functioning among high-suicide risk outpatients participating in an adjunct mindfulness-based intervention combining mindfulness-based cognitive therapy and safety planning (MBCT-S). DESIGN: Ten outpatients with a 6-month history of suicide attempt or active suicidal ideation plus suicidal ideation at study entry received 9 weeks of adjunct group-based MBCT-S. Executive attention, sustained attention, visual memory, and semantic memory encoding were measured by neuropsychological assessment. Rumination, mindfulness, cognitive reactivity (defined as the tendency towards depressogenic information processing and thought content in response to mild mood deterioration), and self-compassion were assessed using self-report measures. Changes in pre- to post-treatment functioning on these constructs were analyzed by using dependent t-tests. Where significant improvements were found, correlations between changes to cognitive functioning and depression and suicidal ideation during treatment were calculated. RESULTS: Executive attention improved with MBCT-S in high-suicide risk outpatients (Stroop interference effect = 0.39 [standard deviation (SD), 27] at baseline and 0.27 (SD, 0.15) at post-treatment, t[9] = 2.35, p = 0.04, d = 0.75). One mindfulness skill, acting with awareness, increased with MBCT-S (average change in Five Facet Mindfulness Questionnaire-acting with awareness subscale score with treatment, 3.3 [SD, 3.0], t[9] = 3.46, p < 0.01, d = 1.1). Self-reported rumination and cognitive reactivity to suicidality and hopelessness decreased among participants (Ruminative Responses Brooding subscale score change, -3.4 [SD, 1.1], t[9] = 10, p < 0.001, d = 3.2; Leiden Index of Depression Sensitivity-Revised-Hopelessness/Suicidality subscale score change, -3 [SD, 2.7], t[9] = 3.56, p < 0.01, d = 1.1). None of these changes were related to improvements in depression or reductions in suicidal ideation during treatment. CONCLUSIONS: Findings from the present pilot study suggest that treatment with MBCT-S may improve cognitive deficits specific to suicide ideators and attempters among depressed patients. Future controlled trials using follow-up assessments are needed to determine the specificity of these improvements in cognitive functioning to MBCT-S and their durability and to formally test whether the observed improvements in cognitive functioning explain MBCT-S treatment gains.

Reviewing Mindfulness-Based Interventions for Suicidal Behavior.

This article describes the rationale for using mindfulness-based interventions (MBIs) to prevent suicidal behavior in high suicide-risk individuals. A narrative review of studies testing the feasibility of MBIs with individuals at risk for suicidal behavior and the effectiveness of MBIs for reducing suicidality was conducted. Studies testing the effectiveness of MBIs for reducing deficits specific to suicide attempters among depressed individuals were also reviewed as were studies examining moderators of MBI treatment adherence and effectiveness to the extent that these might suggest possible limitations to using MBIs with high suicide-risk individuals. Findings from the handful of available studies support targeting suicidal ideation with MBI. Additional studies show deficits associated with suicide attempt, namely attentional dyscontrol, problem solving deficits, and abnormal stress response, are improved by MBI and thus strengthen the rationale for using MBIs with high suicide-risk individuals.