Evaluation of Bait Crops for the Integrated Management of White Rot (Sclerotium cepivorum) in Allium Crops.

White rot, caused by Sclerotium cepivorum, is a serious disease that causes significant yield losses in Allium production. The pathogen persists in soil as sclerotia, which germinate in response to sulfur compounds in Allium root exudates. This study was aimed at investigating the potential of early-terminated Allium bait crops to reduce densities of S. cepivorum sclerotia in soil. In growth chamber experiments with white onion (A. cepa cultivar 'Southport White Globe'), red onion (A. cepa cultivar 'Marenge'), sweet onion (A. cepa cultivar 'Walla Walla'), and bunching onion (A. fistulosum cultivar 'Parade'), termination of all four Alliums at the first- and second-leaf stages reduced soil sclerotia populations by up to 62 and 76%, respectively. Examination of soil samples collected 4 weeks after crop termination indicated that sclerotia populations in bait crop treatments remained low when seedlings were terminated at the first- and second-leaf stages. In contrast, crop termination at the third-leaf stage resulted in an increase in sclerotia counts due to the pathogen reproduction on the bait crops. The reduction in sclerotia populations in soil due to early crop termination was also observed in replicated field trials. Greater reductions in sclerotia counts were observed when plants in these experiments were terminated chemically as opposed to mechanically. In-furrow fungicides did not reduce sclerotia numbers under the conditions tested. This study demonstrates the potential for early termination of Allium bait crops to help reduce white rot inoculum in soil.

Comprehensive ECG reference intervals in C57BL/6N substrains provide a generalizable guide for cardiac electrophysiology studies in mice.

Reference ranges provide a powerful tool for diagnostic decision-making in clinical medicine and are enormously valuable for understanding normality in pre-clinical scientific research that uses in vivo models. As yet, there are no published reference ranges for electrocardiography (ECG) in the laboratory mouse. The first mouse-specific reference ranges for the assessment of electrical conduction are reported herein generated from an ECG dataset of unprecedented scale. International Mouse Phenotyping Consortium data from over 26,000 conscious or anesthetized C57BL/6N wildtype control mice were stratified by sex and age to develop robust ECG reference ranges. Interesting findings include that heart rate and key elements from the ECG waveform (RR-, PR-, ST-, QT-interval, QT corrected, and QRS complex) demonstrate minimal sexual dimorphism. As expected, anesthesia induces a decrease in heart rate and was shown for both inhalation (isoflurane) and injectable (tribromoethanol) anesthesia. In the absence of pharmacological, environmental, or genetic challenges, we did not observe major age-related ECG changes in C57BL/6N-inbred mice as the differences in the reference ranges of 12-week-old compared to 62-week-old mice were negligible. The generalizability of the C57BL/6N substrain reference ranges was demonstrated by comparison with ECG data from a wide range of non-IMPC studies. The close overlap in data from a wide range of mouse strains suggests that the C57BL/6N-based reference ranges can be used as a robust and comprehensive indicator of normality. We report a unique ECG reference resource of fundamental importance for any experimental study of cardiac function in mice.

Pathophysiology, prevention, and treatment of beriberi after gastric surgery.

Beriberi is a nutritional complication of gastric surgery, caused by deficiency of vitamin B1, or thiamine. Thiamine deficiency leads to impaired glucose metabolism, decreased delivery of oxygen by red blood cells, cardiac dysfunction, failure of neurotransmission, and neuronal death. This review describes the history and pathophysiology of beriberi as well as the relationship between beriberi and nutritional deficiencies after gastric surgery. A literature review of the history and pathophysiology of beriberi and the risk factors for thiamine deficiency, particularly after gastric resection or bariatric surgery, was performed. Recommendations for nutritional follow-up post gastric surgery are based on current national guidelines. Patients may have subclinical thiamine deficiency after upper gastrointestinal surgery, and thus beriberi may be precipitated by acute illness such as sepsis or poor dietary intake. This may occur very soon or many years after gastrectomy or bariatric surgery, even in apparently well-nourished patients. Prompt recognition and administration of supplemental thiamine can decrease morbidity and mortality in patients with beriberi. Dietary education post surgery and long-term follow-up to determine nutritional status, including vitamin and mineral assessment, is recommended for patients who undergo gastric surgery.

Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity.

Environmental factors are the largest contributors to cardiovascular disease. Here we show that cardiac organoids that incorporate an oxygen-diffusion gradient and that are stimulated with the neurotransmitter noradrenaline model the structure of the human heart after myocardial infarction (by mimicking the infarcted, border and remote zones), and recapitulate hallmarks of myocardial infarction (in particular, pathological metabolic shifts, fibrosis and calcium handling) at the transcriptomic, structural and functional levels. We also show that the organoids can model hypoxia-enhanced doxorubicin cardiotoxicity. Human organoids that model diseases with non-genetic pathological factors could help with drug screening and development.

Water Birth Maternal and Neonatal Outcomes Among Midwifery Clients in Alberta, Canada, from 2014 to 2017: A Retrospective Study.

OBJECTIVES: This study sought to evaluate retrospectively the maternal and neonatal outcomes of water births (WBs) managed by Registered Midwives in Alberta compared with traditional or "land" vaginal birth outcomes for clinical evidence or knowledge and to assist in health care management planning. METHODS: This study was a retrospective cohort comparison of maternal and neonatal outcomes of WB (1716) and traditional or land birth (non-WB) (21 320) from selected low-risk maternal cohorts with spontaneous onset of labour and vaginal delivery in Alberta (2014-2017) using Alberta Perinatal Health Program data sets. Anonymized client and patient records linked the Alberta Perinatal Health Program data with inpatient Discharge Abstract Database for newborn and/or maternal personal health number (PHN/ULI) analyzed using SPSS 19.0 software (IBM Corp., Armonk, NY) (Canadian Task Force Classification II-2). RESULTS: The WB group had fewer and less severe perineal lacerations despite increased macrosomia. The non-WB group had increased maternal factors (age <20 years, third- to fourth-degree perineal tears, excessive blood loss) and neonatal factors (Apgar scores <7 at 5 minutes and neonatal intensive care unit admission). No significant difference was identified between the birth groups for maternal age >35 years, primiparous status, maternal fever, maternal puerperal infection, maternal intensive care unit admission, low birth weight, neonatal resuscitation, and neonatal intensive care unit admission <28 days of life. CONCLUSIONS: A low-risk maternal cohort of WBs (1716) managed by midwives had equivalent or improved neonatal outcomes compared with a low-risk maternal cohort of land or traditional births (21 320) managed by midwives and other maternity providers.

Comparing the Effects of Two Tillage Operations on Beneficial Epigeal Arthropod Communities and Their Associated Ecosystem Services in Sugar Beets.

Beneficial arthropods provide important ecosystem services in terms of arthropod pest and weed management, but these services can be adversely affected by farming practices such as tillage. This study investigated the impact of two tillage operations (zone tillage and moldboard plow) on the activity density of several beneficial, epigeal arthropod taxa, and postdispersal weed seed and prey removal in sugar beet agroecosystems. In addition, four omnivorous ground beetle species were selected for a weed-seed choice feeding assay, whereas a single species was selected for a weed-seed age preference assay. Ground beetles were the most commonly collected taxon (via pitfall sampling), with only a few dominant species. Tillage operation did not affect ground beetle activity density; however, spider, centipede, and rove beetle activity densities were higher in the reduced-tillage treatment. Live prey consumption was similar between tillage practices, with more prey consumed during nocturnal hours. More weed seeds were consumed in the reduced-tillage treatment, whereas weed-seed preference differed between the four weed species tested [Setaria pumila (Poir.) Roem. & Schult., Echinochloa crus-galli (L.), Kochia scoparia (L.), and Chenopodium album (L.)]. In the weed-seed choice feeding assay, significantly more broad-leaf weed seeds (C. album and K. scoparia) were consumed compared with grassy weed seeds (E. crus-galli and S. pumila). No preference for seed age was detected for E. crus-galli, but Harpalus pensylvanicus (De Geer) preferred old C. album seeds over fresh seeds. Zone tillage is compatible with ecosystem services, providing critical habitat within agricultural ecosystems needed to conserve beneficial, edaphic arthropods.

Design, Synthesis, and Pharmacological Evaluation of Second-Generation Tetrahydroisoquinoline-Based CXCR4 Antagonists with Favorable ADME Properties.

CXCR4 is a G-protein-coupled receptor that interacts with its cognate ligand, CXCL12, to synchronize many physiological responses and pathological processes. Disruption of the CXCL12-CXCR4 circuitry by small-molecule antagonists has emerged as a promising strategy for cancer intervention. We previously disclosed a hit-to-lead effort that led to the discovery of a series of tetrahydroisoquinoline-based CXCR4 antagonists exemplified by the lead compound TIQ15. Herein, we describe our medicinal-chemistry efforts toward the redesign of TIQ15 as a result of high mouse-microsomal clearance, potent CYP2D6 inhibition, and poor membrane permeability. Guided by the in vitro ADME data of TIQ15, structural modifications were executed to provide compound 12a, which demonstrated a reduced potential for first-pass metabolism while maintaining CXCR4 potency. Subsequent SAR studies and multiparameter optimization of 12a resulted in the identification of compound 25o, a highly potent, selective, and metabolically stable CXCR4 antagonist possessing good intestinal permeability and low risk of CYP-mediated drug-drug interactions.

Environmental consequences of the flooding of the Bay Park Sewage Treatment Plant during Superstorm Sandy.

Failure of the Bay Park Sewage Treatment Plant (STP) during Superstorm Sandy led to adverse effects in the waters of Hempstead Bay, Long Island, NY. These appear to be related to large discharges of partially treated sewage through its primary and auxiliary outfalls. Modeled dilution discharges indicate that sewage infiltrated the bay, remaining up to 10days. Water column impacts included salinity and dissolved oxygen declines, and biological oxygen demand and nitrogen concentration increases. While the STP does not appear to have released fecal coliform, there were elevated levels of enterococci within the bay for a considerable period following the storm, probably from multiple sources. The STP's reduced functioning and associated environmental impacts, even with resilience upgrades, are not conducive to removing the bay from the list of Impaired Water Bodies. The results reinforce the need to transfer the discharge from the existing outfall to the ocean.

The RESPIRE trials: Two phase III, randomized, multicentre, placebo-controlled trials of Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) in non-cystic fibrosis bronchiectasis.

The primary goals of long-term disease management in non-cystic fibrosis bronchiectasis (NCFB) are to reduce the number of exacerbations, and improve quality of life. However, currently no therapies are licensed for this. Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) has potential to be the first long-term intermittent therapy approved to reduce exacerbations in NCFB patients. The RESPIRE programme consists of two international phase III prospective, parallel-group, randomized, double-blinded, multicentre, placebo-controlled trials of the same design. Adult patients with idiopathic or post-infectious NCFB, a history of ≥2 exacerbations in the previous 12months, and positive sputum culture for one of seven pre-specified pathogens, undergo stratified randomization 2:1 to receive twice-daily Ciprofloxacin DPI 32.5mg or placebo using a pocket-sized inhaler in one of two regimens: 28days on/off treatment or 14days on/off treatment. The treatment period is 48weeks plus an 8-week follow-up after the last dose. The primary efficacy endpoints are time to first exacerbation after treatment initiation and frequency of exacerbations using a stringent definition of exacerbation. Secondary endpoints, including frequency of events using different exacerbation definitions, microbiology, quality of life and lung function will also be evaluated. The RESPIRE trials will determine the efficacy and safety of Ciprofloxacin DPI. The strict entry criteria and stratified randomization, the inclusion of two treatment regimens and a stringent definition of exacerbation should clarify the patient population best positioned to benefit from long-term inhaled antibiotic therapy. Additionally RESPIRE will increase understanding of NCFB treatment and could lead to an important new therapy for sufferers. TRIAL REGISTRATION: The RESPIRE trials are registered in ClinicalTrials.gov, ID number NCT01764841 (RESPIRE 1; date of registration January 8, 2013) and NCT02106832 (RESPIRE 2; date of registration April 4, 2014).

Regular Latin Dancing and Health Education May Improve Cognition of Late Middle-Aged and Older Latinos.

Disparities exist between Latinos and non-Latino Whites in cognitive function. Dance is culturally appropriate and challenges individuals physically and cognitively, yet the impact of regular dancing on cognitive function in older Latinos has not been examined. A two-group pilot trial was employed among inactive, older Latinos. Participants (N = 57) participated in the BAILAMOS© dance program or a health education program. Cognitive test scores were converted to z-scores and measures of global cognition and specific domains (executive function, episodic memory, working memory) were derived. Results revealed a group × time interaction for episodic memory (p < .05), such that the dance group showed greater improvement in episodic memory than the health education group. A main effect for time for global cognition (p < .05) was also demonstrated, with participants in both groups improving. Structured Latin dance programs can positively influence episodic memory, and participation in structured programs may improve overall cognition among older Latinos.

Evaluation of selenium in dietary supplements using elemental speciation.

Selenium-enriched dietary supplements containing various selenium compounds are readily available to consumers. To ensure proper selenium intake and consumer confidence, these dietary supplements must be safe and have accurate label claims. Varying properties among selenium species requires information beyond total selenium concentration to fully evaluate health risk/benefits A LC-ICP-MS method was developed and multiple extraction methods were implemented for targeted analysis of common "seleno-amino acids" and related oxidation products, selenate, selenite, and other species relatable to the quality and/or accuracy of the labeled selenium ingredients. Ultimately, a heated water extraction was applied to recover selenium species from non-selenized yeast supplements in capsule, tablet, and liquid forms. For selenized yeast supplements, inorganic selenium was monitored as a means of assessing selenium yeast quality. A variety of commercially available selenium supplements were evaluated and discrepancies between labeled ingredients and detected species were noted.

Systems analysis of the prostate transcriptome in African-American men compared with European-American men.

AIM: African-Americans (AA) have increased prostate cancer risk and a greater mortality rate than European-Americans (EA). AA exhibit a high prevalence of vitamin D deficiency. We examined the global prostate transcriptome in AA and EA, and the effect of vitamin D3 supplementation. PATIENTS & METHODS: Twenty-seven male subjects (ten AA and 17 EA), slated to undergo prostatectomy were enrolled in the study. Fourteen subjects received vitamin D3 (4000 IU daily) and 13 subjects received placebo for 2 months prior to surgery. RESULTS: AA show higher expression of genes associated with immune response and inflammation. CONCLUSION: Systems level analyses support the concept that Inflammatory processes may contribute to disease progression in AA. These transcripts can be modulated by a short course of vitamin D3 supplementation.

Prognostic factors for clinical failure of exacerbations in elderly outpatients with moderate-to-severe COPD.

BACKGROUND: Acute exacerbations represent a significant burden for patients with moderate-to-severe chronic obstructive pulmonary disease. Each exacerbation episode is frequently associated with a lengthy recovery and impaired quality of life. Prognostic factors for outpatients that may predict poor outcome after treatment with antibiotics recommended in the guidelines, are not fully understood. We aimed to identify pretherapy factors predictive of clinical failure in elderly (≥60 years old) outpatients with acute Anthonisen type 1 exacerbations. TRIAL REGISTRATION: NCT00656747. METHODS: Based on the moxifloxacin in AECOPDs (acute exacerbations of chronic obstructive pulmonary disease) trial (MAESTRAL) database, this study evaluated pretherapy demographic, clinical, sputum bacteriological factors using multivariate logistic regression analysis, with internal validation by bootstrap replicates, to investigate their possible association with clinical failure at end of therapy (EOT) and 8 weeks posttherapy. RESULTS: The analyses found that the independent factors predicting clinical failure at EOT were more frequent exacerbations, increased respiratory rate and lower body temperature at exacerbation, treatment with long-acting anticholinergic drugs, and in vitro bacterial resistance to study drug. The independent factors predicting poor outcome at 8 weeks posttherapy included wheezing at preexacerbation, mild or moderate (vs extreme) sleep disturbances, lower body temperature at exacerbation, forced expiratory volume in 1 second <30%, lower body mass index, concomitant systemic corticosteroids for the current exacerbation, maintenance long-acting ß2-agonist and long-acting anticholinergic treatments, and positive sputum culture at EOT. CONCLUSION: Several bacteriological, historical, treatment-related factors were identified as predictors of early (EOT) and later (8 weeks posttherapy) clinical failure in this older outpatient population with moderate-to-severe chronic obstructive pulmonary disease. These patients should be closely monitored and sputum cultures considered before and after treatment.

Mito-nuclear discord in six congeneric lineages of Holarctic ducks (genus Anas).

Many species have Holarctic distributions that extend across Europe, Asia and North America. Most genetics research on these species has examined only mitochondrial (mt) DNA, which has revealed wide variance in divergence between Old World (OW) and New World (NW) populations, ranging from shallow, unstructured genealogies to deeply divergent lineages. In this study, we sequenced 20 nuclear introns to test for concordant patterns of OW-NW differentiation between mtDNA and nuclear (nu) DNA for six lineages of Holarctic ducks (genus Anas). Genetic differentiation for both marker types varied widely among these lineages (idiosyncratic population histories), but mtDNA and nuDNA divergence within lineages was not significantly correlated. Moreover, compared with the association between mtDNA and nuDNA divergence observed among different species, OW-NW nuDNA differentiation was generally lower than mtDNA divergence, at least for lineages with deeply divergent mtDNA. Furthermore, coalescent estimates indicated significantly higher rates of gene flow for nuDNA than mtDNA for four of the six lineages. Thus, Holarctic ducks show prominent mito-nuclear discord between OW and NW populations, and we reject differences in sorting rates as the sole cause of the within-species discord. Male-mediated intercontinental gene flow is likely a leading contributor to this discord, although selection could also cause increased mtDNA divergence relative to weak nuDNA differentiation. The population genetics of these ducks contribute to growing evidence that mtDNA can be an unreliable indicator of stage of speciation and that more holistic approaches are needed for species delimitation.

Copper- and palladium-catalyzed amidation reactions for the synthesis of substituted imidazo[4,5-c]pyridines.

Imidazo[4,5-c]pyridines were synthesized in three steps utilizing a palladium-catalyzed amidation/cyclization strategy. N-Aryl substrates were synthesized using copper-catalyzed amidation of 3-amino-N-Boc-4-chloropyridine. Complementary protocols for the selective chlorination of imidazo[4,5-c]pyridines at the C2 and C7 positions were also developed.

Hyperbaric oxygen therapy for systemic gas embolism after hydrogen peroxide ingestion.

BACKGROUND: Hydrogen peroxide is a commonly available product and its ingestion has been demonstrated to produce in vivo gas bubbles, which can embolize to devastating effect. OBJECTIVE: We report two cases of hydrogen peroxide ingestion with resultant gas embolization, one to the portal system and one cerebral embolus, which were successfully treated with hyperbaric oxygen therapy (HBO), and review the literature. CASE REPORT: Two individuals presented to our center after unintentional ingestion of concentrated hydrogen peroxide solutions. Symptoms were consistent with portal gas emboli (Patient A) and cerebral gas emboli (Patient B), which were demonstrated on imaging. They were successfully treated with HBO and recovered without event. CONCLUSIONS: As demonstrated by both our experience as well as the current literature, HBO has been used to successfully treat gas emboli associated with hydrogen peroxide ingestion. We recommend consideration of HBO in any cases of significant hydrogen peroxide ingestion with a clinical picture compatible with gas emboli.

Zinc Detection in Serum by Anodic Stripping Voltammetry on Microfabricated Bismuth Electrodes.

Zinc (Zn) homeostasis is required for a functional immune system. Critically ill patients often exhibit decreased Zn serum concentrations and could potentially benefit from Zn supplementation as a therapeutic strategy. However, the conventional approaches to monitoring Zn are time consuming and costly. This work reports on detection of Zn by anodic stripping voltammetry (ASV) on bismuth electrodes in a microfabricated electrochemical cell. The working potential window of the electrodeposited bismuth film electrode was investigated by cyclic voltammetry, while square wave ASV was used for measuring Zn in acetate buffer and blood serum. Conditions critical to sensing, such as preconcentration potential, preconcentration time, and buffer pH, were optimized for Zn detection. The sensor was successfully calibrated with pH 6 acetate buffer in the physiologically-relevant range of 5 µM to 50µM Zn and exhibited well-defined and highly repeatable peaks. The sensor was used to demonstrate measurement of Zn in blood serum digested in HCl. The results of this work show that Zn detection in serum is possible with smaller sample volumes (µL vs. µL) and faster turnaround time (hours vs. days) as compared with the conventional spectroscopic methods.

The use of moxifloxacin for acute exacerbations of chronic obstructive pulmonary disease and chronic bronchitis.

Chronic obstructive pulmonary disease is a common condition which causes considerable morbidity and mortality. It is a heterogenous disorder in which the majority of patients have chronic bronchitis. Bacterial infections are a major cause of acute exacerbations of both conditions which have a major impact on healthcare resources, quality of life and disease progression. Antibiotics are used to treat exacerbations involving purulent sputum production, together with increased breathlessness and/or sputum volume. Moxifloxacin is a quinolone antibiotic and is one of the treatment options. This article discusses pathophysiology of these diseases, moxifloxacin clinical studies and appropriate use of moxifloxacin.

A0001 in Friedreich ataxia: biochemical characterization and effects in a clinical trial.

This study tested the ability of A0001 (α-tocopheryl quinone; EPI-A0001), a potent antioxidant, to improve in vitro measures, glucose metabolism, and neurological function in Friedreich ataxia. We used an in vitro study of protection from cell toxicity followed by a double-blind, randomized, placebo-controlled trial of 2 doses of A0001 in 31 adults with Friedreich ataxia. The primary clinical trial outcome was the Disposition Index, a measure of diabetic tendency, from a frequently sampled intravenous glucose tolerance test, evaluated 4 weeks into therapy. Secondary neurologic measures included the Friedreich Ataxia Rating Scale. A0001 potently inhibited cell death in Friedreich ataxia models in vitro. For the clinical trial, mean guanine-adenine-adenine repeat length was 699, and mean age was 31 years. Four weeks after treatment initiation, differences in changes in the Disposition Index between subjects treated with A0001 and placebo were not statistically significant. In contrast, a dose-dependent improvement in the Friedreich Ataxia Rating Scale score was observed. Patients on placebo improved 2.0 rating scale points, whereas patients on low-dose A0001 improved by 4.9 points (P = .04) and patients on a high dose improved by 6.1 points (P < .01). Although A0001 did not alter the Disposition Index, it caused a dose-dependent improvement in neurologic function, as measured by the Friedreich Ataxia Rating Scale. Longer studies will assess the reproducibility and persistence of neurologic benefit.

Primary and secondary drug screening assays for Friedreich ataxia.

Friedreich ataxia (FRDA) is an autosomal recessive neuro- and cardiodegenerative disorder for which there are no proven effective treatments. FRDA is caused by decreased expression and/or function of the protein frataxin. Frataxin chaperones iron in the mitochondrial matrix for the assembly of iron-sulfur clusters (ISCs), which are prosthetic groups critical for the function of the Krebs cycle and the mitochondrial electron transport chain (ETC). Decreased expression of frataxin or the yeast frataxin orthologue, Yfh1p, is associated with decreased ISC assembly, mitochondrial iron accumulation, and increased oxidative stress, all of which contribute to mitochondrial dysfunction. Using yeast depleted of Yfh1p, a high-throughput screening (HTS) assay was developed in which mitochondrial function was monitored by reduction of the tetrazolium dye WST-1 in a growth medium with a respiration-only carbon source. Of 101 200 compounds screened, 302 were identified that effectively rescue mitochondrial function. To confirm activities in mammalian cells and begin understanding mechanisms of action, secondary screening assays were developed using murine C2C12 cells and yeast mutants lacking specific complexes of the ETC, respectively. The compounds identified in this study have potential relevance for other neurodegenerative disorders associated with mitochondrial dysfunction, such as Parkinson disease.