Nanosecond solvation dynamics in a polymer electrolyte for lithium batteries.

Solvation dynamics critically affect charge transport. Spectroscopic experiments and computer simulations show that these dynamics in aqueous systems occur on a picosecond timescale. In the case of organic electrolytes, however, conflicting values ranging from 1 to several 100 picoseconds have been reported. We resolve this conflict by studying mixtures of an organic polymer and a lithium salt. Lithium ions coordinate with multiple polymer chains, resulting in temporary crosslinks. Relaxation of these crosslinks, detected by quasielastic neutron scattering, are directly related to solvation dynamics. Simulations reveal a broad spectrum of relaxation times. The average timescale for solvation dynamics in both experiment and simulation is one nanosecond. We present the direct measurement of ultraslow dynamics of solvation shell break-up in an electrolyte.

Evaluation of lead-based echodensities on transesophageal echocardiogram in patients with cardiac implantable electronic devices.

INTRODUCTION: Transesophageal echocardiography (TEE) is recommended to rule out endocarditis in patients with cardiac implantable electronic devices (CIED). A lead-based echodensity (LBE), however, is often found on TEE in patients with a CIED and may not represent an infection. We sought to evaluate the predictors, characteristics, and clinical significance of LBEs seen on TEE in patients with a CIED. METHODS: Patients with a CIED were retrospectively identified from a database using International Classification of Diseases (ICD)-9/ICD-10 codes and were cross-matched with Current Procedural Terminology codes for a TEE. Clinical and follow-up data were collected. A blinded echo board-certified cardiologist reviewed all TEEs. RESULTS: Out of the 231 patients in the cohort, 191 had TEE performed for a noninfection-related indication while 40 TEEs were part of an endocarditis workup. A total of 50 LBEs were identified, and a majority were in the noninfection cohort. Systemic anticoagulant use in the noninfection cohort was associated with a decreased odds of having LBE on TEE (odds ratio [OR] of 0.23 [95% confidence interval [CI]: 0.06-0.60, p = .003]). Lead dwell time in the noninfection cohort was associated with an increased odds of having LBE on TEE (OR 1.21 (95% CI: 1.04-1.39, p = .009]). CONCLUSION: In our cohort of patients who had TEE for noninfection indications we found that systemic anticoagulant use is associated with fewer LBEs on TEEs, suggesting possible thrombin fibrin composition of LBE.

Engineered Chimeras Unveil Swappable Modular Features of Fatty Acid and Polyketide Synthase Acyl Carrier Proteins.

The strategic redesign of microbial biosynthetic pathways is a compelling route to access molecules of diverse structure and function in a potentially environmentally sustainable fashion. The promise of this approach hinges on an improved understanding of acyl carrier proteins (ACPs), which serve as central hubs in biosynthetic pathways. These small, flexible proteins mediate the transport of molecular building blocks and intermediates to enzymatic partners that extend and tailor the growing natural products. Past combinatorial biosynthesis efforts have failed due to incompatible ACP-enzyme pairings. Herein, we report the design of chimeric ACPs with features of the actinorhodin polyketide synthase ACP (ACT) and of the Escherichia coli fatty acid synthase (FAS) ACP (AcpP). We evaluate the ability of the chimeric ACPs to interact with the E. coli FAS ketosynthase FabF, which represents an interaction essential to building the carbon backbone of the synthase molecular output. Given that AcpP interacts with FabF but ACT does not, we sought to exchange modular features of ACT with AcpP to confer functionality with FabF. The interactions of chimeric ACPs with FabF were interrogated using sedimentation velocity experiments, surface plasmon resonance analyses, mechanism-based cross-linking assays, and molecular dynamics simulations. Results suggest that the residues guiding AcpP-FabF compatibility and ACT-FabF incompatibility may reside in the loop I, α-helix II region. These findings can inform the development of strategic secondary element swaps that expand the enzyme compatibility of ACPs across systems and therefore represent a critical step toward the strategic engineering of "un-natural" natural products.

Redefining Healthy Urine: A Cross-Sectional Exploratory Metagenomic Study of People With and Without Bladder Dysfunction.

PURPOSE: We used the PathoScope platform to perform species level analyses of publicly available, 16S rRNA pyrosequenced, asymptomatic urine data to determine relationships between microbiomes, and clinical and functional phenotypes. MATERIALS AND METHODS: We reanalyzed previously reported, cross-sectionally acquired urine samples from 47 asymptomatic subjects, including 23 controls and 24 subjects with neuropathic bladder. Urine was originally collected by the usual method of bladder drainage and analyzed by urinalysis, culture and pyrosequencing. Urinalysis and culture values were stratified as leukocyte esterase (0, or 1 or greater), nitrite (positive or negative), pyuria (fewer than 5, or 5 or greater white blood cells per high power field), cloudy urine (positive or negative) and urine culture bacterial growth (less than 50,000, or 50,000 or greater cfu/ml). PathoScope was used for next generation sequencing alignment, bacterial classification and microbial diversity characterization. RESULTS: Subjects with neuropathic bladder were significantly more likely to have positive leukocyte esterase and pyuria, cloudy urine and bacterial growth. Of 47 samples 23 showed bacterial growth on culture and in all samples bacteria were identified by pyrosequencing. Nonneuropathic bladder urine microbiomes included greater proportions of Lactobacillus crispatus in females and Staphylococcus haemolyticus in males. The Lactobacillus community differed significantly among females depending on bladder function. Irrespective of gender the subjects with neuropathic bladder had greater proportions of Enterococcus faecalis, Proteus mirabilis and Klebsiella pneumonia. In 4 subjects with neuropathic bladder Actinobaculum sp. was detected by sequencing and by PathoScope but not by cultivation and in all cases it was associated with pyuria. CONCLUSIONS: Using PathoScope plus 16S pyrosequencing we were able to identify unique, phenotype dependent, species level microbes. Novel findings included absent L. crispatus in the urine of females with neuropathic bladder and the presence of Actinobaculum only in subjects with neuropathic bladder.

Management of toxicities following pelvic irradiation for gynaecological cancers.

PURPOSE OF REVIEW: With increasing numbers of cancer survivors, management of the consequences of treatment is a major clinical problem. This article discusses recent advances in preventing and managing radiotherapy-related toxicity. RECENT FINDINGS: Often underreported in clinical studies, radiation toxicity should be assessed with validated assessment tools to assess impact on quality of life. Prevention strategies targeting reactive oxygen species and proinflammatory cytokines show promise. Bowel toxicity is the most common late effect, and algorithm-led investigation and management can significantly improve outcomes. Oral and intravesical therapies are options for bladder toxicity if conservative measures fail. SUMMARY: With better understanding of the mechanisms of acute and chronic radiation-induced changes, more effective treatments are now possible. Following pelvic radiotherapy, patients should be proactively assessed for early intervention by a specialist multidisciplinary team.

Efficacy of a Bio-Absorbable Antibacterial Envelope to Prevent Cardiac Implantable Electronic Device Infections in High-Risk Subjects.

INTRODUCTION: Cardiac implantable electronic device (CIED) infections are potentially preventable complications associated with high morbidity, mortality, and cost. A recently developed bio-absorbable antibacterial envelope (TYRX™-A) might prevent CIED infections in high-risk subjects. However, data regarding safety and efficacy have not been published. METHODS AND RESULTS: In a single-center retrospective cohort study, we compared the prevalence of CIED infections among subjects with ≥2 risk factors treated with the TYRX™-A envelope (N = 135), the nonabsorbable TYRX™ envelope (N = 353), and controls who did not receive an envelope (N = 636). Infection was ascertained by individual chart review. The mean (95% confidence interval) number of risk factors was 3.08 (2.84-3.32) for TYRX™-A, 3.20 (3.07-3.34) for TYRX™, and 3.09 (2.99-3.20) for controls, P = 0.3. After a minimum 300 days follow-up, the prevalence of CIED infection was 0 (0%) for TYRX™-A, 1 (0.3%) for TYRX™, and 20 (3.1%) for controls (P = 1 for TYRX™-A vs. TYRX™, P = 0.03 for TYRX™-A vs. controls, and P = 0.002 for TYRX™ vs. controls). In a propensity score-matched cohort of 316 recipients of either envelope and 316 controls, the prevalence of infection was 0 (0%) and 9 (2.8%), respectively, P = 0.004. When limited to 122 TYRX™-A recipients and 122 propensity-matched controls, the prevalence of CIED infections was 0 (0%) and 5 (4.1%), respectively, P = 0.024. CONCLUSIONS: Among high-risk subjects, the TYRX™-A bio-absorbable envelope was associated with a very low prevalence of CIED related infections that was comparable to that seen with the nonabsorbable envelope.

Cilostazol and freedom from amputation after lower extremity revascularization.

OBJECTIVE: Cilostazol, an antiplatelet agent with vasodilating properties, has not been well evaluated in conjunction lower extremity revascularization (LER). We evaluated the association between cilostazol and limb salvage after endovascular or open surgery for LER. METHODS: Patients aged ≥65 years undergoing LER were identified from 2007 to 2008 Medicare Provider Analysis and Review and Carrier files using International Classification of Diseases-9 Edition-Clinical Modification and Current Procedural Terminology-4 codes. Covariates included demographics, comorbidities, and disease severity. Use of cilostazol was identified using National Drug Codes and Part D files. Outcomes were compared using χ(2) and Kaplan-Meier analyses and Cox regression. RESULTS: We identified 22,954 patients undergoing LER: 8128 (35.4%) with claudication, 3056 (13.3%) with rest pain, and 11,770 (51.3%) with ulceration/gangrene. Among them, 1999 patients (8.7%) used cilostazol before LER. More patients received endovascular (14,353) than open (8601) procedures. Cilostazol users had fewer amputations than nonusers at 30 days (7.8% vs 13.4%), 90 days (10.7% vs 18.0%), and 1 year (14.8% vs 24.0%; P < .0001 for all). Cox proportional hazards regression with adjustment for age, gender, race, comorbidities, type of procedure, and atherosclerosis severity showed noncilostazol users were more likely to undergo amputation ≤1 year after surgery (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.02-1.29; P = .02). Subgroup analyses using Cox proportional hazards models adjusted for age, gender, and comorbidities demonstrated significantly improved 1-year amputation-free survival for patients with renal failure (HR, 1.61; 95% CI, 1.28-2.02; P < .001) and diabetes (HR, 1.61; 95% CI, 1.36-1.92; P < .001) who were taking cilostazol. CONCLUSIONS: In patients undergoing LER, cilostazol use was associated with improved 1-year freedom from amputation. Patients with renal failure and diabetes also demonstrated a significant benefit from taking cilostazol. Further studies are needed to evaluate the benefits of cilostazol after LER.

Monitoring Exposure to Ebola and Health of U.S. Military Personnel Deployed in Support of Ebola Control Efforts - Liberia, October 25, 2014-February 27, 2015.

In response to the unprecedented Ebola virus disease (Ebola) outbreak in West Africa, the U.S. government deployed approximately 2,500 military personnel to support the government of Liberia. Their primary missions were to construct Ebola treatment units (ETUs), train health care workers to staff ETUs, and provide laboratory testing capacity for Ebola. Service members were explicitly prohibited from engaging in activities that could result in close contact with an Ebola-infected patient or coming in contact with the remains of persons who had died from unknown causes. Military units performed twice-daily monitoring of temperature and review of exposures and symptoms ("unit monitoring") on all persons throughout deployment, exit screening at the time of departure from Liberia, and post-deployment monitoring for 21 days at segregated, controlled monitoring areas on U.S. military installations. A total of 32 persons developed a fever during deployment from October 25, 2014, through February 27, 2015; none had a known Ebola exposure or developed Ebola infection. Monitoring of all deployed service members revealed no Ebola exposures or infections. Given their activity restrictions and comprehensive monitoring while deployed to Liberia, U.S. military personnel constitute a unique population with a lower risk for Ebola exposure compared with those working in the country without such measures.

The costs of human inbreeding and their implications for variations at the DNA level.

An analysis of the world literature on the children of first cousin marriages reveals that the depression of survival in offspring followed from birth (including late miscarriages; at about six months gestation or later) to a median age of 10 years is constant (4.4% +/- 4.6) across a wide range of values for population prereproductive mortality. There is thus no evidence for the action of conditional lethals. On the basis of these data, it is calculated that the average human is heterozygous for only 1.4 lethal equivalents capable of acting over this portion of the life cycle. The implications of these results are discussed in the context of genetic counseling, and the biomedical significance of variation in DNA.

Chimney-Shaped Phase Diagram in a Polymer Blend Electrolyte.

The phase behavior of polymer blend electrolytes comprising poly(ethylene oxide) (PEO)/poly(methyl methacrylate) (PMMA)/lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) was determined using a combination of light and small angle neutron scattering (SANS) experiments. The results at a fixed temperature (110 °C) are presented on a PEO concentration versus salt (LiTFSI) concentration plot. The blends are miscible at all PEO concentrations in the absence of salt. With added salt, a region of immiscibility is obtained in PEO-lean polymer blend electrolytes; blends rich in PEO remain miscible at most salt concentrations. A narrow region of immiscibility juts into the miscible region, giving the phase diagram a chimney-like appearance. The data are qualitatively consistent with a simple extension of Flory-Huggins theory with a composition-dependent Flory-Huggins interaction parameter, χ, that was determined independently from SANS data from homogeneous blend electrolytes. Phase diagrams like the one we obtained were anticipated by self-consistent field theory calculations that account for correlations between ions. The relationship between these theories and measured χ remains to be established.

Hematologic changes after total body irradiation and autologous transplantation of hematopoietic peripheral blood progenitor cells in dogs with lymphoma.

Dogs with and without lymphoma have undergone hematopoietic cell transplantation in a research setting for decades. North Carolina State University is currently treating dogs with B- and T-cell lymphoma in a clinical setting with autologous peripheral blood progenitor cell transplants, using peripheral blood CD34+ progenitor cells harvested using an apheresis machine. Complete blood counts were performed daily for 15 to 19 days posttransplantation to monitor peripheral blood cell nadirs and subsequent CD34+ cell engraftment. This study documents the hematologic toxicities of total body irradiation in 10 dogs and the subsequent recovery of the affected cell lines after peripheral blood progenitor cell transplant, indicating successful CD34+ engraftment. All peripheral blood cell lines, excluding red blood cells, experienced grade 4 toxicities. All dogs had ≥ 500 neutrophils/µl by day 12, while thrombocytopenia persisted for many weeks. All dogs were clinically normal at discharge.

Comparison of Bolus Dosing of Methohexital and Propofol in Elective Direct Current Cardioversion.

Background Methohexital and propofol can both be used as sedation for direct current cardioversion (DCCV). However, there are limited data comparing these medications in this setting. We hypothesized that patients receiving methohexital for elective DCCV would be sedated more quickly, recover from sedation faster, and experience less adverse effects. Methods and Results This was a prospective, blinded randomized controlled trial conducted at a single academic medical center. Eligible participants were randomly assigned to receive either methohexital (0.5 mg/kg) or propofol (0.8 mg/kg) as a bolus for elective DCCV. The times from bolus of the medication to achieving a Ramsay Sedation Scale score of 5 to 6, first shock, eyes opening on command, and when the patient could state their age and name were obtained. The need for additional medication dosing, airway intervention, vital signs, and medication side effects were also recorded. Seventy patients who were randomized to receive methohexital (n=37) or propofol (n=33) were included for analysis. The average doses of methohexital and propofol were 0.51 mg/kg and 0.84 mg/kg, respectively. There were no significant differences between methohexital and propofol in the time from end of injection to loss of conscious (1.4±1.8 versus 1.1±0.5 minutes; P=0.33) or the time to first shock (1.7±1.9 versus 1.4±0.5 minutes; P=0.31). Time intervals were significantly lower for methohexital compared with propofol in the time to eyes opening on command (5.1±2.5 versus 7.8±3.7 minutes; P=0.0005) as well as at the time to the ability to answer simple questions of age and name (6.0±2.6 versus 8.6±4.0 minutes; P=0.001). The methohexital group experienced less hypotension (8.1% versus 42.4%; P<0.001) and less hypoxemia (0.0% versus 15.2%; P=0.005), had lower need for jaw thrust/chin lift (16.2% versus 42.4%; P=0.015), and had less pain on injection compared with propofol using the visual analog scale (7.2±9.7 versus 22.4±28.1; P=0.003). Conclusions In this model of fixed bolus dosing, methohexital was associated with faster recovery, more stable hemodynamics, and less hypoxemia after elective DCCV compared with propofol. It can be considered as a preferred agent for sedation for DCCV. Registration URL: https://www.clinicaltrials.gov/ct; Unique identifier: NCT04187196.

Intracellular Chloride Channels: Novel Biomarkers in Diseases.

Ion channels are integral membrane proteins present on the plasma membrane as well as intracellular membranes. In the human genome, there are more than 400 known genes encoding ion channel proteins. Ion channels are known to regulate several cellular, organellar, and physiological processes. Any mutation or disruption in their function can result in pathological disorders, both common or rare. Ion channels present on the plasma membrane are widely acknowledged for their role in various biological processes, but in recent years, several studies have pointed out the importance of ion channels located in intracellular organelles. However, ion channels located in intracellular organelles are not well-understood in the context of physiological conditions, such as the generation of cellular excitability and ionic homeostasis. Due to the lack of information regarding their molecular identity and technical limitations of studying them, intracellular organelle ion channels have thus far been overlooked as potential therapeutic targets. In this review, we focus on a novel class of intracellular organelle ion channels, Chloride Intracellular Ion Channels (CLICs), mainly documented for their role in cardiovascular, neurophysiology, and tumor biology. CLICs have a single transmembrane domain, and in cells, they exist in cytosolic as well as membranous forms. They are predominantly present in intracellular organelles and have recently been shown to be localized to cardiomyocyte mitochondria as well as exosomes. In fact, a member of this family, CLIC5, is the first mitochondrial chloride channel to be identified on the molecular level in the inner mitochondrial membrane, while another member, CLIC4, is located predominantly in the outer mitochondrial membrane. In this review, we discuss this unique class of intracellular chloride channels, their role in pathologies, such as cardiovascular, cancer, and neurodegenerative diseases, and the recent developments concerning their usage as theraputic targets.

Understanding the effects of pasture type and stocking rate on the hydrology of the Southern Great Plains.

Grassland is one of the major biomes in the United States (US) and the world. In the US, the majority of grasslands are concentrated in the Great Plains and has undergone through significant interventions or management changes over the last few decades. A key economy-driven intervention in the Southern Great Plains (SGP) include the introduction of new forage species and conversion of native grassland to introduced pasture to increase productivity and its nutritive value for improved cattle production. Since water is one of the fundamental resources needed to sustain grassland productivity, it is important to understand how such pasture conversion and prevailing cattle grazing practices affect water balance and biomass production in a given pasture system. In this study, the Nutrient Tracking Tool (NTT) with its core APEX (Agricultural Policy Environmental eXtender) model was used to assess the hydrological impacts of the pasture introduction, i.e., native pasture (little bluestem, Schizachyrium halapense) vs. introduced pasture (old world bluestem, Bothriochloa caucasica), and the stocking rate in the SGP. Monthly evapotranspiration (ET) and biomass estimates from NTT compared well with observed data at two USDA-ARS experimental pastures (native and introduced) near El Reno, Oklahoma, for the years 2015 and 2016. Simulated long-term average annual hydrologic fluxes (i.e., ET, runoff, and groundwater recharge) from the introduced pasture were slightly lower than the observed data but not significantly different than those from the native pasture under the current management conditions. NTT predicted higher water yield (runoff and recharge) and significantly lower ET for the introduced pasture than the native pasture. Results suggest that grazing has the potential to alter the hydrological balance in the SGP. For example, the increase in stocking rate within the carrying capacity of the farm decreases ET and increases runoff and groundwater recharge for both pastures. Comparison of estimated biomass production between native and introduced pastures indicated that introduced pastures are more efficient in using the available water and thus produce a higher forage biomass per unit of water in the SGP. This study highlighted the potential significance of considering hydrological and other biophysical impacts of new forage introduction and stocking rate changes for the sustainable management of grazing and pasture systems in the SGP.

Genetic effects of the atomic bombs: a reappraisal.

Data are presented on four indicators of genetic effects from studies of children born to survivors of the atomic bombings of Hiroshima and Nagasaki. The indicators are frequency of untoward pregnancy outcomes (stillbirth, major congenital defect, death during the first postnatal weak); occurrence of death in live-born children, through an average of life expectancy of 17 years; frequency of children with sex chromosome aneuploidy; and frequency of children with mutation resulting in an eletrophoretic variant. In no instance is there a statistically significant effect of parental exposure; but for all indicators the observed effect is in the direction suggested by the hypothesis that genetic damage resulted from the exposure. On the basis of assumptions concerning the contribution that spontaneous mutation in the preceding generation makes to the indicators in question, it is possible to estimate the genetic doubling dose for radiation for the first three indicators (the data base is still too small for the fourth). The average of these estimates is 156 rems. This is some four times higher than the results from experimental studies on the mouse with comparable radiation sources, which have been the principal guide to the presumed human sensitivities. The relevance of these data in setting permissible limits for human exposures is discussed briefly.

Atrial Fibrillation Ablation: Indications and Techniques.

PURPOSE OF REVIEW: Atrial fibrillation (AF) predisposes to embolic strokes and reduced quality of life. Ablation (catheter-based or surgically performed) can be employed to promote the maintenance of sinus rhythm in a carefully selected subset of patients with AF. The goal of this review is to discuss the indications and techniques for AF ablation, as well as post-procedural outcomes. RECENT FINDINGS: Atrial fibrillation ablation improves quality of life in patients with atrial fibrillation although no clear reduction in stroke or overall mortality has been shown. Familiarity with the indications for AF ablation is important for all cardiologists, as is having a sound understanding of the efficacy of the procedure and potential complications. Furthermore, acquiring a grasp of the different modalities of AF ablation (including percutaneous endocardial techniques and surgical ablation approaches) will help to facilitate effective and appropriate referrals.

Influence of finishing systems on hydrophilic and lipophilic oxygen radical absorbance capacity (ORAC) in beef.

The aim of this research was to: (1) develop a reliable extraction procedure and assay to determine antioxidant activity in meat products, and (2) assess the effect of beef finishing system (forage-finished: alfalfa, pearl millet or mixed pastures vs. concentrate-finished) on longissimus muscle antioxidant activity. The effect of extraction method (ethanol concentration and extraction time), protein removal, and sample preparation method (pulverization or freeze drying) were first evaluated to develop an antioxidant assay for meat products. Beef extracts prepared with low ethanol concentrations (20%) demonstrated higher hydrophilic ORAC. Protein removal prior to extraction reduced hydrophilic ORAC values. Sample preparation method influenced both hydrophilic and lipophilic ORAC, with pulverized samples containing higher hydrophilic and lipophilic ORAC values. Beef cattle finishing system (Forage: alfalfa, pearl millet, or natural pasture vs. concentrates) had little impact on muscle hydrophilic ORAC, but muscle from forage finished beef contained greater lipophilic ORAC. In addition, broiling of steaks reduced hydrophilic ORAC.

Three Decades of Chloride Intracellular Channel Proteins: From Organelle to Organ Physiology.

Intracellular organelles are membranous structures central for maintaining cellular physiology and the overall health of the cell. To maintain cellular function, intracellular organelles are required to tightly regulate their ionic homeostasis. Any imbalance in ionic concentrations can disrupt energy production (mitochondria), protein degradation (lysosomes), DNA replication (nucleus), or cellular signaling (endoplasmic reticulum). Ionic homeostasis is also important for volume regulation of intracellular organelles and is maintained by cation and anion channels as well as transporters. One of the major classes of ion channels predominantly localized to intracellular membranes is chloride intracellular channel proteins (CLICs). They are non-canonical ion channels with six homologs in mammals, existing as either soluble or integral membrane protein forms, with dual functions as enzymes and channels. Provided in this overview is a brief introduction to CLICs, and a summary of recent information on their localization, biophysical properties, and physiological roles. © 2018 by John Wiley & Sons, Inc.

Inhibition of BKCa negatively alters cardiovascular function.

Large conductance calcium and voltage-activated potassium channels (BKCa ) are transmembrane proteins, ubiquitously expressed in the majority of organs, and play an active role in regulating cellular physiology. In the heart, BKCa channels are known to play a role in regulating the heart rate and protect it from ischemia-reperfusion injury. In vascular smooth muscle cells, the opening of BKCa channels results in membrane hyperpolarization which eventually results in vasodilation mediated by a reduction in Ca2+ influx due to the closure of voltage-dependent Ca2+ channels. Ex vivo studies have shown that BKCa channels play an active role in the regulation of the function of the majority of blood vessels. However, in vivo role of BKCa channels in cardiovascular function is not completely deciphered. Here, we have evaluated the rapid in vivo role of BKCa channels in regulating the cardiovascular function by using two well-established, rapid-acting, potent blockers, paxilline and iberiotoxin. Our results show that BKCa channels are actively involved in regulating the heart rate, the function of the left and right heart as well as major vessels. We also found that the effect on BKCa channels by blockers is completely reversible, and hence, BKCa channels can be exploited as potential targets for clinical applications for modulating heart rate and cardiac contractility.

Identification of Burkholderia fungorum in the urine of an individual with spinal cord injury and augmentation cystoplasty using 16S sequencing: copathogen or innocent bystander?

INTRODUCTION: People with neuropathic bladder (NB) secondary to spinal cord injury (SCI) are at risk for multiple genitourinary complications, the most frequent of which is urinary tract infection (UTI). Despite the high frequency with which UTI occurs, our understanding of the role of urinary microbes in health and disease is limited. In this paper, we present the first prospective case study integrating symptom reporting, urinalysis, urine cultivation, and 16S ribosomal ribonucleic acid (rRNA) sequencing of the urine microbiome. CASE PRESENTATION: A 55-year-old male with NB secondary to SCI contributed 12 urine samples over an 8-month period during asymptomatic, symptomatic, and postantibiotic periods. All bacteria identified on culture were present on 16S rRNA sequencing, however, 16S rRNA sequencing revealed the presence of bacteria not isolated on culture. In particular, Burkholderia fungorum was present in three samples during both asymptomatic and symptomatic periods. White blood cells of ≥5-10/high power field and leukocyte esterase ≥2 on urinalysis was associated with the presence of symptoms. DISCUSSION: In this patient, there was a predominance of pathogenic bacteria and a lack of putative probiotic bacteria during both symptomatic and asymptomatic states. Urinalysis-defined inflammatory markers were present to a greater extent during symptomatic periods compared to the asymptomatic state, which may underscore a role for urinalysis or other inflammatory markers in differentiating asymptomatic bacteriuria from UTI in patients with NB. The finding of potentially pathogenic bacteria identified by sequencing but not cultivation, suggests a need for greater understanding of the relationships amongst bacterial species in the bacteriuric neuropathic bladder.