The Gut Microbiome, Metformin, and Aging.

Metformin has been extensively used for the treatment of type 2 diabetes, and it may also promote healthy aging. Despite its widespread use and versatility, metformin's mechanisms of action remain elusive. The gut typically harbors thousands of bacterial species, and as the concentration of metformin is much higher in the gut as compared to plasma, it is plausible that microbiome-drug-host interactions may influence the functions of metformin. Detrimental perturbations in the aging gut microbiome lead to the activation of the innate immune response concomitant with chronic low-grade inflammation. With the effectiveness of metformin in diabetes and antiaging varying among individuals, there is reason to believe that the gut microbiome plays a role in the efficacy of metformin. Metformin has been implicated in the promotion and maintenance of a healthy gut microbiome and reduces many age-related degenerative pathologies. Mechanistic understanding of metformin in the promotion of a healthy gut microbiome and aging will require a systems-level approach.

Getting off tract: contributions of intraorgan microbiota to cancer in extraintestinal organs.

The gastrointestinal ecosystem has received the most attention when examining the contributions of the human microbiome to health and disease. This concentration of effort is logical due to the overwhelming abundance of microbes in the gut coupled with the relative ease of sampling compared with other organs. However, the intestines are intimately connected to multiple extraintestinal organs, providing an opportunity for homeostatic microbial colonisation and pathogenesis in organs traditionally thought to be sterile or only transiently harbouring microbiota. These habitats are challenging to sample, and their low microbial biomass among large amounts of host tissue can make study challenging. Nevertheless, recent findings have shown that many extraintestinal organs that are intimately linked to the gut harbour stable microbiomes, which are colonised from the gut in selective manners and have highlighted not just the influence of the bacteriome but that of the mycobiome and virome on oncogenesis and health.

The role of environmental variation in mediating fitness trade-offs for an amphibian polyphenism.

Fitness trade-offs are a foundation of ecological and evolutionary theory because trade-offs can explain life history variation, phenotypic plasticity, and the existence of polyphenisms. Using a 32-year mark-recapture dataset on lifetime fitness for 1093 adult Arizona tiger salamanders (Ambystoma mavortium nebulosum) from a high elevation, polyphenic population, we evaluated the extent to which two life history morphs (aquatic paedomorphs vs. terrestrial metamorphs) exhibited fitness trade-offs in breeding and body condition with respect to environmental variation (e.g. climate) and internal state-based variables (e.g. age). Both morphs displayed a similar response to higher probabilities of breeding during years of high spring precipitation (i.e. not indicative of a morph-specific fitness trade-off). There were likely no climate-induced fitness trade-offs on breeding state for the two life history morphs because precipitation and water availability are vital to amphibian reproduction. Body condition displayed a contrasting response for the two morphs that was indicative of a climate-induced fitness trade-off. While metamorphs exhibited a positive relationship with summer snowpack conditions, paedomorphs were unaffected. Fitness trade-offs from summer snowpack are likely due to extended hydroperiods in temporary ponds, where metamorphs gain a fitness advantage during the summer growing season by exploiting resources that are unavailable to paeodomorphs. However, paedomorphs appear to have the overwintering fitness advantage because they consistently had higher body condition than metamorphs at the start of the summer growing season. Our results reveal that climate and habitat type (metamorphs as predominately terrestrial, paedomorphs as fully aquatic) interact to confer different advantages for each morph. These results advance our current understanding of fitness trade-offs in this well-studied polyphenic amphibian by integrating climate-based mechanisms. Our conclusions prompt future studies to explore how climatic variation can maintain polyphenisms and promote life history diversity, as well as the implications of climate change for polyphenisms.

Breast cancer survivors' physical activity and experiences while transitioning to a virtual cardiovascular rehabilitation program during a pandemic (COVID-19).

Breast cancer accounts for 25% of all cancers among Canadian females. Despite successes of decreased mortality, adverse treatment effects, such as cardiotoxicity, contribute to a sedentary lifestyle and decreased quality of life. Physical activity (PA) is a possible therapy for the late effects; however, COVID-19 restricted access to in-person cardiovascular rehabilitation (CR) programs. The purposes are as follows: (1) compare PA of breast cancer survivors' in-person CR to virtual CR following a transition during COVID-19 and (2) compare the PA of the pandemic cohort to a matched cohort who had completed the program in 2018/2019; (3) explore survivors' experiences of transitioning to and engaging in virtual CR. Mixed methods included analysis of CR PA data from a pandemic cohort (n = 18) and a 2018/2019 cohort (n = 18) and semi-structured focus group interviews with the pandemic cohort (n = 9) in the context of the PRECEDE-PROCEED model. After the transition, there were no significant differences in mean activity duration, frequency, and cumulative activity (expressed as MET-minutes) (p > 0.05). However, variation of PA duration doubled following the transition from in-person to virtual (p = 0.029), while for the 2018/2019 cohort, variation remained unchanged. Focus groups revealed that women valued their CR experiences pre-COVID-19 and had feelings of anxiety during the transition. Perceived factors affecting participation were environmental, personal, and behavioural. Recommendations for virtual programs were to increase comradery, technology, and professional guidance. PA experiences during a transition to virtual care prompted by a pandemic vary among breast cancer survivors. Targeting individualised strategies and exercise prescriptions are important for improving PA programs and patient outcomes.

Diagnostic Value of Lactate Dehydrogenase and Uric Acid as Screening Tools for Malignancies in Children.

OBJECTIVE: The aim of this study was to determine the diagnostic value of lactate dehydrogenase (LDH) and uric acid (UA) in children undergoing evaluation for possible malignancies. METHODS: This was a retrospective chart review of patients aged 0 to 18 years presenting to an urban, tertiary care, pediatric hospital between July 1, 2011, and July 1, 2016. Patients were included if they had an LDH and/or UA level drawn, and they were excluded if they had a known cancer diagnosis. Sensitivity, specificity, and receiver operating characteristic curves were calculated for each biomarker. RESULTS: Six hundred five subjects were included in this study; 579 and 384 subjects had LDH and UA levels drawn, respectively; 15.7% had a final diagnosis of malignancy (49 leukemia, 46 nonleukemia). CONCLUSION: The specificities of both biomarkers for all types of malignancies were lower than their respective sensitivities. Comparing leukemic versus nonleukemic malignancies, the areas under the curve were 0.848 and 0.719, respectively, for LDH and 0.681 and 0.555, respectively, for UA.

Muscle Oxygenation of the Paretic and Nonparetic Legs During and After Arterial Occlusion in Chronic Stroke.

Oxygen delivery and demand are reduced in the paretic leg post-stroke, reflecting decreased vascular function and reduced muscle quantity and quality. However, it is unknown how muscle oxygenation, the balance between muscle oxygen delivery and utilization, is altered in chronic stroke during and after occlusion-induced ischemia. OBJECTIVES: The objective was to determine muscle oxygen consumption rate, microvascular responsiveness and reactive hyperemia in the paretic and nonparetic legs during and after arterial occlusion post-stroke. MATERIALS AND METHODS: Muscle oxygen saturation was measured with near-infrared spectroscopy on the vastus lateralis of each leg during 3-minute arterial occlusion and recovery (3 min). Muscle oxygen consumption was derived from the desaturation slope during ischemia, microvascular responsiveness was derived from the resaturation slope after ischemia and reactive hyperemia was derived from the area under the curve above baseline after ischemia. RESULTS: Eleven subjects (91% male; 32.2±6.1 months post-stroke; age 62.9±13.6 years) with a hemiparetic gait pattern participated. There was no significant between-leg muscle oxygenation difference at rest (paretic: 64.9±16.6%; nonparetic: 70.6±15.6%, p = 0.13). Muscle oxygen consumption in the paretic leg (-0.53±0.24%/s) was significantly reduced compared to the nonparetic leg (-0.70±0.36%/s; p = 0.03). Microvascular responsiveness was significantly reduced in the paretic leg compared to the nonparetic leg (paretic: 4.6±1.8%/s; nonparetic: 5.7±1.6%/s, p = 0.04). Reactive hyperemia was not significantly different between legs (paretic:4384±2341%·s; nonparetic: 3040±2216%·s, p = 0.07). CONCLUSION: Muscle oxygen consumption and microvascular responsiveness are impaired in the paretic compared to the nonparetic leg, suggesting both reduced skeletal muscle aerobic function and reduced ability to maximally perfuse muscle tissue.

Altered expression of fragile X mental retardation-1 (FMR1) in the thymus in autoimmune myasthenia gravis.

Predisposition to autoimmunity and inflammatory disorders is observed in patients with fragile X-associated syndromes. These patients have increased numbers of CGG triplets in the 5' UTR region of FMR1 (Fragile X Mental Retardation 1) gene, that affects its expression. FMR1 is decreased in the thymus of myasthenia gravis (MG) patients, a prototypical autoimmune disease. We thus analyzed the number of CGG triplets in FMR1 in MG, and explored the regulatory mechanisms affecting thymic FMR1 expression. We measured the number of CGGs using thymic DNA from MG and controls, but no abnormalities in CGGs were found in MG that could explain thymic decrease of FMR1. We next analyzed by RT-PCR the expression of FMR1 and its transcription factors in thymic samples, and in thymic epithelial cell cultures in response to inflammatory stimuli. In control thymuses, FMR1 expression was higher in males than females, and correlated with CTCF (CCCTC-binding factor) expression. In MG thymuses, decreased expression of FMR1 was correlated with both CTCF and MAX (Myc-associated factor X) expression. Changes in FMR1 expression were supported by western blot analyses for FMRP. In addition, we demonstrated that FMR1, CTCF and MAX expression in thymic epithelial cells was also sensitive to inflammatory signals. Our results suggest that FMR1 could play a central role in the thymus and autoimmunity. First, in relation with the higher susceptibility of females to autoimmune diseases. Second, due to the modulation of its expression by inflammatory signals that are known to be altered in MG thymuses.

Effect of exercise training on cardiovascular autonomic and muscular function in subclinical Chagas cardiomyopathy: a randomized controlled trial.

PURPOSE: Patients with chronic chagasic cardiomyopathy with preserved ventricular function present with autonomic imbalance. This study evaluated the effects of exercise training (ET) in restoring peripheral and cardiac autonomic control and skeletal muscle phenotype in patients with subclinical chronic chagasic cardiomyopathy. METHODS: This controlled trial (NCT02295215) included 24 chronic chagasic cardiomyopathy patients who were randomized www.random.org/lists/ into two groups: those who underwent exercise training (n = 12) and those who continued their usual activities (n = 12). Eight patients completed the exercise training protocol, and 10 patients were clinically followed up for 4 months. Muscular sympathetic nerve activity was measured by microneurography and muscle blood flow (MBF) using venous occlusion plethysmography. The low-frequency component of heart rate variability in normalized units (LFnuHR) reflects sympathetic activity in the heart, and the low-frequency component of systolic blood pressure variability in normalized units reflects sympathetic activity in the vessels. The infusion of vasoactive drugs (phenylephrine and sodium nitroprusside) was used to evaluate cardiac baroreflex sensitivity, and a vastus lateralis muscle biopsy was performed to evaluate atrogin-1 and MuRF-1 gene expression. RESULTS: The baroreflex sensitivity for increases (p = 0.002) and decreases (p = 0.02) in systolic blood pressure increased in the ET group. Muscle blood flow also increased only in the ET group (p = 0.004). Only the ET group had reduced resting muscular sympathetic nerve activity levels (p = 0.008) and sympathetic activity in the heart (LFnu; p = 0.004) and vessels (p = 0.04) after 4 months. Regarding skeletal muscle, after 4 months, participants in the exercise training group presented with lower atrogin-1 gene expression than participants who continued their activities as usual (p = 0.001). The reduction in muscular sympathetic nerve activity was positively associated with reduced atrogin-1 (r = 0.86; p = 0.02) and MuRF-1 gene expression (r = 0.64; p = 0.06); it was negatively associated with improved baroreflex sensitivity both for increases (r = -0.72; p = 0.020) and decreases (r = -0.82; p = 0.001) in blood pressure. CONCLUSIONS: ET improved cardiac and peripheral autonomic function in patients with subclinical chagasic cardiomyopathy. ET reduced MSNA and sympathetic activity in the heart and vessels and increased cardiac parasympathetic tone and baroreflex sensitivity. Regarding peripheral muscle, after 4 months, patients who underwent exercise training had an increased cross-sectional area of type I fibers and oxidative metabolism of muscle fibers, and decreased atrogin-1 gene expression, compared to participants who continued their activities as usual. In addition, the reduction in MSNA was associated with improved cardiac baroreflex sensitivity, reduced sympathetic cardiovascular tone, and reduced atrogin-1 and MuRF-1 gene expression. TRIAL REGISTRATION: ID: NCT02295215. Registered in June 2013.

Regulation of Glucose Metabolism by MuRF1 and Treatment of Myopathy in Diabetic Mice with Small Molecules Targeting MuRF1.

The muscle-specific ubiquitin ligase MuRF1 regulates muscle catabolism during chronic wasting states, although its roles in general metabolism are less-studied. Here, we metabolically profiled MuRF1-deficient knockout mice. We also included knockout mice for MuRF2 as its closely related gene homolog. MuRF1 and MuRF2-KO (knockout) mice have elevated serum glucose, elevated triglycerides, and reduced glucose tolerance. In addition, MuRF2-KO mice have a reduced tolerance to a fat-rich diet. Western blot and enzymatic studies on MuRF1-KO skeletal muscle showed perturbed FoxO-Akt signaling, elevated Akt-Ser-473 activation, and downregulated oxidative mitochondrial metabolism, indicating potential mechanisms for MuRF1,2-dependent glucose and fat metabolism regulation. Consistent with this, the adenoviral re-expression of MuRF1 in KO mice normalized Akt-Ser-473, serum glucose, and triglycerides. Finally, we tested the MuRF1/2 inhibitors MyoMed-205 and MyoMed-946 in a mouse model for type 2 diabetes mellitus (T2DM). After 28 days of treatment, T2DM mice developed progressive muscle weakness detected by wire hang tests, but this was attenuated by the MyoMed-205 treatment. While MyoMed-205 and MyoMed-946 had no significant effects on serum glucose, they did normalize the lymphocyte-granulocyte counts in diabetic sera as indicators of the immune response. Thus, small molecules directed to MuRF1 may be useful in attenuating skeletal muscle strength loss in T2DM conditions.

Diagnosis and Treatment of Trauma-Induced Coagulopathy by Viscoelastography.

This article explores the application of viscoelastic tests (VETs) in trauma-induced coagulopathy and trauma resuscitation. We describe the advantages of VETs over conventional coagulation tests in the trauma setting and refer to previous disciplines in which VET use has reduced blood product utilization, guided prohemostatic agents, and improved clinical outcomes such as the mortality of critically bleeding patients. We describe different VETs and provide guidance for blood component therapy and prohemostatic therapy based on specific VET parameters. Because the two most commonly used VET systems, rotational thromboelastometry and thromboelastography, use different activators and have different terminologies, this practical narrative review will directly compare and contrast these two VETs to help the clinician easily interpret either and use the interpretation to determine hemostatic integrity in the bleeding trauma patient. Finally, we anticipate the future of new viscoelastic technologies that can be used in this setting.

Whole Blood for Civilian Urban Trauma Resuscitation: Historical, Present, and Future Considerations.

Whole blood (WB) has been used for more than a century for far-forward combat resuscitation. Following the Iraq/Afghanistan combat, maritime, and austere environment use of WB for the resuscitation of severely hemorrhaging patients, there has been an increasing use of WB for the civilian urban resuscitation environment population. The impetus for this was not just improved outcomes in far-forward hospitals, which had different populations and different needs than the civilian urban population, but also an application of the lessons suggested by recent 1:1:1 plasma:platelets:packed red cells fixed-ratio studies for patients with massive transfusion needs. Mechanistic, logistic, and standardization concerns have been addressed and are evolving as the WB project advances. A small number of studies have been published on WB in the civilian urban trauma population. In addition, European experience with viscoelastic testing and resuscitation with fibrinogen and prothrombin complex concentrate has provided another viewpoint regarding the choice of resuscitation strategies for severely bleeding trauma patients in urban civilian environments. There are randomized controlled trials in process, which are testing the hypothesis that WB may be beneficial for the civilian urban population. Whether WB will improve mortality significantly is now a matter of intense study, and this commentary reviews the history, mechanistic foundations, and logistical aspects for the use of WB in the civilian trauma population.

Viscoelastic testing in oncology patients (including for the diagnosis of fibrinolysis): Review of existing evidence, technology comparison, and clinical utility.

The quantification of the coagulopathic state associated with oncologic and hematologic diseases is imperfectly assessed by common coagulation tests such as prothrombin time, activated partial thromboplastin time, fibrinogen levels, and platelet count. These tests provide a static representation of a component of hemostatic integrity, presenting an incomplete picture of coagulation in these patients. Viscoelastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), as whole blood analyses, provide data related to the cumulative effects of blood components and all stages of the coagulation and fibrinolytic processes. The utility of VETs has been demonstrated since the late 1960s in guiding blood component therapy for patients undergoing liver transplantation. Since then, the scope of viscoelastic testing has expanded to become routinely used for cardiac surgery, obstetrics, and trauma. In the past decade, VETs' expanded usage has been most significant in trauma resuscitation. However, use of VETs for patients with malignancy-associated coagulopathy (MAC) and hematologic malignancies is increasing. For the purposes of this narrative review, we discuss the similarities between trauma-induced coagulopathy (TIC) and MAC. These similarities center on the thrombomodulin-thrombin complex as it switches between the thrombin-activatable fibrinolysis inhibitor coagulation pathway and activating the protein C anticoagulation pathway. This produces a spectrum of coagulopathy and fibrinolytic alterations ranging from shutdown to hyperfibrinolysis that are common to TIC, MAC, and hematologic malignancies. There is expanding literature regarding the utility of TEG and ROTEM to describe the hemostatic integrity of patients with oncologic and hematologic conditions, which we review here.

Diverse respiratory capacity among Thermus strains from US Great Basin hot springs.

Thermus species are thermophilic heterotrophs, with most capable of using a variety of organic and inorganic electron donors for respiration. Here, a combined cultivation-independent and -dependent approach was used to explore the diversity of Thermus in Great Boiling Spring (GBS) and Little Hot Creek (LHC) in the US Great Basin. A cultivation-independent 16S rRNA gene survey of ten LHC sites showed that Thermus made up 0-3.5% of sequences and were predominately Thermus thermophilus. 189 Thermus isolates from GBS and LHC were affiliated with T. aquaticus (73.0%), T. oshimai (25.4%), T. sediminis (1.1%), and T. thermophilus (0.5%), with T. aquaticus and T. oshimai forming biogeographic clusters. 22 strains were selected for characterization, including chemolithotrophic oxidation of thiosulfate and arsenite, and reduction of ferric iron, polysulfide, and nitrate, revealing phenotypic diversity and broad respiratory capability within each species. PCR demonstrated the wide distribution of aerobic arsenite oxidase genes. A GBS sediment metaproteome contained sulfite oxidase and Fe3+ ABC transporter permease peptides, suggesting sulfur and iron transformations in situ. This study expands our knowledge of the physiological diversity of Thermus, suggesting widespread chemolithotrophic and anaerobic respiration phenotypes, and providing a foundation for better understanding the ecology of this genus in thermal ecosystems.

Short-Term Resistance Training Improves Cardiac Autonomic Modulation and Blood Pressure in Hypertensive Older Women: A Randomized Controlled Trial.

Oliveira-Dantas, FF, Brasileiro-Santos, MdS, Thomas, SG, Silva, AS, Silva, DC, Browne, RAV, Farias-Junior, LF, Costa, EC, and Santos, AdC. Short-term resistance training improves cardiac autonomic modulation and blood pressure in hypertensive older women: a randomized controlled trial. J Strength Cond Res 34(1): 37-45, 2020-This randomized controlled trial investigated the efficacy of short-term resistance training (RT) on cardiac autonomic modulation and peripheral hemodynamic parameters in hypertensive older women. Twenty-five hypertensive older women who were insufficiently active (64.7 ± 4.7 years) participated in this study. Subjects were randomly allocated to a 10-week RT program (2 d·wk in the first 5 weeks; 3 d·wk in the last 5 weeks) or a nonexercise control group. Linear reverse periodization was used for the RT program. Cardiac autonomic modulation, mean blood pressure (MBP), peripheral vascular resistance (PVR), and resting heart rate (RHR) were measured before and after 10 weeks. The RT group reduced cardiac sympathetic modulation (0V%; B = -6.6; 95% confidence interval [CI]: -12.9 to -0.2; p = 0.045; Cohen's d = 0.88) and showed a trend for increased parasympathetic modulation (2V%; B = 12.5; 95% CI: 0-25; p = 0.050; Cohen's d = 0.87) compared with the control group. The RT group reduced MBP (B = -8.5 mm Hg; 95% CI: -13.6 to -3.4; p = 0.001; Cohen's d = 1.27), PVR (B = -14.1 units; 95% CI: -19.9 to -8.4; p < 0.001; Cohen's d = 1.86), and RHR (B = -8.8 b·min; 95% CI: -14.3 to -3.3; p = 0.002; Cohen's d = 1.20) compared with the control group. In the RT group, the changes in 2V% patterns and low-frequency components showed a correlation with changes in MBP (r = -0.60; p = 0.032) and RHR (r = 0.75; p = 0.0003). In conclusion, 10 weeks of RT improved cardiac autonomic modulation and reduced MBP and PVR in hypertensive older women. These results reinforce the importance of RT for this population.

Use of Viscoelastography in Malignancy-Associated Coagulopathy and Thrombosis: A Review.

The relationship between malignancy and coagulopathy is one that is well documented yet incompletely understood. Clinicians have attempted to quantify the hypercoagulable state produced in various malignancies using common coagulation tests such as prothrombin time, activated partial thromboplastin time, and platelet count; however, due to these tests' focus on individual aspects of coagulation during one specific time point, they have failed to provide clinicians the complete picture of malignancy-associated coagulopathy (MAC). Viscoelastic tests (VETs), such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), are whole blood analyses that have the advantage of providing information related to the cumulative effects of plasma clotting factors, platelets, leukocytes, and red cells during all stages of the coagulation and fibrinolytic processes. VETs have gained popularity in the care of trauma patients to objectively measure trauma-induced coagulopathy (TIC), but the utility of VETs remains yet unrealized in many other medical specialties. The authors discuss the similarities and differences between TIC and MAC, and propose a mechanism for the hypercoagulable state of MAC that revolves around the thrombomodulin-thrombin complex as it switches between activating the protein C anticoagulation pathway or the thrombin activatable fibrinolysis inhibitor coagulation pathway. Additionally, they review the current literature on the use of TEG and ROTEM in patients with various malignancies. Although limited research is currently available, early results demonstrate the utility of both TEG and ROTEM in the prediction of hypercoagulable states and thromboembolic complications in oncologic patients.

Fibrinolysis Shutdown in Trauma: Historical Review and Clinical Implications.

Despite over a half-century of recognizing fibrinolytic abnormalities after trauma, we remain in our infancy in understanding the underlying mechanisms causing these changes, resulting in ineffective treatment strategies. With the increased utilization of viscoelastic hemostatic assays (VHAs) to measure fibrinolysis in trauma, more questions than answers are emerging. Although it seems certain that low fibrinolytic activity measured by VHA is common after injury and associated with increased mortality, we now recognize subphenotypes within this population and that specific cohorts arise depending on the specific time from injury when samples are collected. Future studies should focus on these subtleties and distinctions, as hypofibrinolysis, acute shutdown, and persistent shutdown appear to represent distinct, unique clinical phenotypes, with different pathophysiology, and warranting different treatment strategies.

Teaching Medical Students in the Rural Setting Long Term: Physicians' Attitudes and Perceptions.

OBJECTIVES: The University of Alabama School of Medicine Tuscaloosa Regional Campus conducted a 2-month block in rural family practice, but committed to expanding to an 8-month longitudinal rural curriculum. We wanted to explore how rural physicians feel about teaching students in a prolonged rural preceptorship. METHODS: We brainstormed with colleagues, reviewed the literature, and conducted two focus groups supplemented by five interviews with rural physicians. The focus groups explored satisfaction and dissatisfaction in teaching, medical school and community support, evaluation of preceptors, and the sharing of information between students and preceptors. The analysis sought common themes among study participants and colleagues. RESULTS: Twenty-one study participants included 19 family physicians, 15 in private practice. Eleven had taught medical students. Our key finding, combining four themes, was that a satisfactory context within which to teach medical students long term in rural sites depends on the optimization of the roles of preceptors, students, communities, and educational institutions. There were comments addressing each of these roles. This finding cannot be generalized beyond the study group because of the qualitative methodology using a convenience sample. CONCLUSIONS: These physicians' concerns foment hypotheses about engaging rural physicians in their own unique local networks involving preceptors, students, community, and educational institutions to conduct satisfactory long-term medical education in rural sites. We recommend investigations to substantiate a prevalence among rural physicians of concern about the four roles and to describe various contexts in which these roles produce satisfactory long-term preceptorships, perhaps as best practices in different settings.

Repeat Intravenous Ketamine Dosing in Children Undergoing Emergency Department Procedural Sedation.

BACKGROUND: Patients undergoing procedural sedation with intravenous ketamine often receive repeat doses to maintain dissociation; however, data between doses are lacking. OBJECTIVES: The purpose of this study was to characterize the frequency, time interval, and dosages of ketamine received by children undergoing procedural sedation and to explore the effects of age and body mass index on these parameters. METHODS: This was a retrospective study of patients 1 to 18 years of age undergoing procedural sedation with intravenous ketamine in a pediatric emergency department between October 2016 and June 2017. Total repeat ketamine dosages were standardized to a 1-h sedation. RESULTS: Four hundred nineteen patients were included in the analysis. The median sedation time was 33.0 minutes (interquartile range [IQR] 25.0-45.0). Three hundred sixty-three patients (86.6%) received at least 1 repeat ketamine dose. The median time between doses was 7.0 minutes (IQR 5.0-12.0). Children <6 years of age, compared with older children, received higher hourly doses of ketamine in mg/kg/h (2.8 [IQR 1.8-3.9] vs. 1.8 [IQR 1.2-2.6], pc < 0.01). Children <3 years of age, compared with older children, received the highest hourly dose of ketamine in mg/kg/h (3.7 [IQR 2.3-5.0] vs. 1.9 [IQR 1.4-2.8], pc < 0.01). Ketamine repeat and hourly dosing does not appear to be significantly different in children of differing body mass index classes. CONCLUSIONS: Patients undergoing ketamine sedation often receive repeat doses to maintain dissociation. Patients <3 years of age received the highest total repeat ketamine dosages.

Mindfulness-Based Yoga for Youth With Persistent Concussion: A Pilot Study.

OBJECTIVE: We explored the potential impact of mindfulness-based yoga (MBY) for youth with persistent concussion by examining occupation-based and neurophysiological outcomes. METHOD: In this case series design study, 6 youths ages 13-17 yr with concussion symptoms for >4 wk participated in an 8-wk MBY intervention, 1×/wk for 45 min. Participation, self-efficacy, and heart rate variability (24 hr) were collected before, after, and 3 mo after the intervention. Heart rate variability was also measured during each session. RESULTS: Trends of increased self-efficacy in academic, social, and emotional domains were found after MBY and maintained at 3-mo follow-up. Trends of increasing heart rate variability were also found pre- to postintervention and within the eight MBY sessions. CONCLUSION: Preliminary results reveal positive trends after a novel, safe intervention for youth with persistent concussion symptoms and the value of exploring both occupation-based and neurophysiological measures. Future research with a larger sample and control group is warranted.

Thermus sediminis sp. nov., a thiosulfate-oxidizing and arsenate-reducing organism isolated from Little Hot Creek in the Long Valley Caldera, California.

Thermus species are widespread in natural and artificial thermal environments. Two new yellow-pigmented strains, L198T and L423, isolated from Little Hot Creek, a geothermal spring in eastern California, were identified as novel organisms belonging to the genus Thermus. Cells are Gram-negative, rod-shaped, and non-motile. Growth was observed at temperatures from 45 to 75 °C and at salinities of 0-2.0% added NaCl. Both strains grow heterotrophically or chemolithotrophically by oxidation of thiosulfate to sulfate. L198T and L423 grow by aerobic respiration or anaerobic respiration with arsenate as the terminal electron acceptor. Values for 16S rRNA gene identity (≤ 97.01%), digital DNA-DNA hybridization (≤ 32.7%), OrthoANI (≤ 87.5%), and genome-to-genome distance (0.13) values to all Thermus genomes were less than established criteria for microbial species. The predominant respiratory quinone was menaquinone-8 and the major cellular fatty acids were iso-C15:0, iso-C17:0 and anteiso-C15:0. One unidentified phospholipid (PL1) and one unidentified glycolipid (GL1) dominated the polar lipid pattern. The new strains could be differentiated from related taxa by ß-galactosidase and ß-glucosidase activity and the presence of hydroxy fatty acids. Based on phylogenetic, genomic, phenotypic, and chemotaxonomic evidence, the novel species Thermus sediminis sp. nov. is proposed, with the type strain L198T (= CGMCC 1.13590T = KCTC XXX).