Microbial Community Response to Granular Peroxide-Based Algaecide Treatment of a Cyanobacterial Harmful Algal Bloom in Lake Okeechobee, Florida (USA).

Cyanobacterial harmful algal blooms (cyanoHABs) occur in fresh water globally. These can degrade water quality and produce toxins, resulting in ecological and economic damages. Thus, short-term management methods (i.e., algaecides) are necessary to rapidly mitigate the negative impacts of cyanoHABs. In this study, we assess the efficacy of a hydrogen peroxide-based algaecide (PAK® 27) on a Microcystis dominated bloom which occurred within the Pahokee Marina on Lake Okeechobee, Florida, USA. We observed a significant reduction in chlorophyll a (96.81%), phycocyanin (93.17%), and Microcystis cell counts (99.92%), and a substantial reduction in microcystins (86.7%) 48 h after treatment (HAT). Additionally, there was a significant shift in bacterial community structure 48 HAT, which coincided with an increase in the relative abundance of photosynthetic protists. These results indicate that hydrogen peroxide-based algaecides are an effective treatment method for cyanoHAB control and highlight their effects on non-target microorganisms (i.e., bacteria and protists).

Do variations in nasal irrigation recipes and storage effect the risk of bacterial contamination?

OBJECTIVE: Make-at-home nasal irrigation solutions are often recommended for treating chronic rhinosinusitis. Many patients will store pre-made solution for convenient use. This study investigated the microbiological properties of differing recipes and storage temperatures. METHOD: Three irrigation recipes (containing sodium chloride, sodium bicarbonate and sucrose) were stored at 5oC and 22oC. Further samples were inoculated with Staphylococcus aureus and Pseudomonas aeruginosa. Sampling and culturing were conducted at intervals from day 0-12 to examine for bacterial presence or persistence. RESULTS: No significant bacterial growth was detected in any control solution stored at 5oC. Saline solutions remained relatively bacterial free, with poor survival of inoculated bacteria, which may be related to either lower pH or lower osmolality. Storing at room temperature increased the risk of contamination in control samples, particularly from pseudomonas. CONCLUSION: If refrigerated, pre-made nasal irrigation solutions can be stored safely for up to 12 days without risking cross-contamination to irrigation equipment or patients.

Common genetic variants do not predict recurrent events in coronary heart disease patients.

BACKGROUND: It is unclear whether genetic variants identified from single nucleotide polymorphisms (SNPs) strongly associated with coronary heart disease (CHD) in genome-wide association studies (GWAS), or a genetic risk score (GRS) derived from them, can help stratify risk of recurrent events in patients with CHD. METHODS: Study subjects were enrolled at the close-out of the LIPID randomised controlled trial of pravastatin vs placebo. Entry to the trial had required a history of acute coronary syndrome 3-36 months previously, and patients were in the trial for a mean of 36 months. Patients who consented to a blood sample were genotyped with a custom designed array chip with SNPs chosen from known CHD-associated loci identified in previous GWAS. We evaluated outcomes in these patients over the following 10 years. RESULTS: Over the 10-year follow-up of the cohort of 4932 patients, 1558 deaths, 898 cardiovascular deaths, 727 CHD deaths and 375 cancer deaths occurred. There were no significant associations between individual SNPs and outcomes before or after adjustment for confounding variables and for multiple testing. A previously validated 27 SNP GRS derived from SNPs with the strongest associations with CHD also did not show any independent association with recurrent major cardiovascular events. CONCLUSIONS: Genetic variants based on individual single nucleotide polymorphisms strongly associated with coronary heart disease in genome wide association studies or an abbreviated genetic risk score derived from them did not help risk profiling in this well-characterised cohort with 10-year follow-up. Other approaches will be needed to incorporate genetic profiling into clinically relevant stratification of long-term risk of recurrent events in CHD patients.

Coping strategies in response to different levels of elevated water hardness in channel catfish (Ictalurus punctatus): Insight into ion-regulatory and histopathological modulations.

Water hardness above the optimal level can incite toxic effects in fish, which are often species specific. Hence, we aimed at obtaining insights on the potential effects of elevated water hardness as well as coping strategies in channel catfish (Ictalurus punctatus). First, a toxicity assay was performed where the 96 h-LC50 was calculated as 4939 mg/L CaCO3. Thereafter, to gain knowledge on the underlying adaptive strategies to high water hardness, fish were exposed to seven hardness levels (150, 600, 1000, 1500, 2000, 3000 and 4000 mg/L CaCO3 at pH 8.15) for 15 days. Results showed that branchial activities of Ca2+-ATPase and Na+/K+-ATPase, which facilitate Ca2+ uptake, reduced starting respectively from 1000 mg/L and 1500 mg/L CaCO3. Nevertheless, Ca2+ burden in plasma and tissue (gills, liver and intestine) remained elevated. Hardness exposure also disturbed cations (Na+, K+, Mg2+) and minerals (iron and phosphorus) homeostasis in a tissue-specific and dose-dependent manner. Both hemoglobin content and hematocrit dropped significantly at 3000-4000 mg/L CaCO3, with a parallel decline in iron content in plasma and gills. Muscle water content rose dramatically at 4000 mg/L CaCO3, indicating an osmo-regulation disruption. Higher hardness of 3000-4000 mg/L CaCO3 also incited a series of histopathological modifications in gills, liver and intestine; most likely due to excess Ca2+ accumulation. Overall, these data suggest that channel catfish can adapt to a wide range of elevated hardness by modulating Ca2+ regulatory pathways and histomorphological alterations, however, 1500 mg/L CaCO3 and above can impair the performance of this species.

Oesophageal cancer: The effect of early nutrition support on clinical outcomes.

BACKGROUND AND AIMS: Malnutrition is prevalent in oesophageal cancer. Evidence for the use of nutrition support and prehabilitation in this cohort is variable. The aim of this study was to examine the effect of early nutrition support and functional measures of nutritional status on post-operative outcomes in adult patients with oesophageal cancer. METHODS: Retrospective review of adults with oesophageal cancer undergoing oesophagectomy (n = 151). Early nutrition support was defined as: oral or enteral nutrition supplementation during neoadjuvant treatment. Late nutrition support defined as: oral or enteral nutrition supplementation prescribed post-operatively. Nutrition outcome measures were; percentage weight loss from 3 to 6 months prior to diagnosis, peri- and post-operatively, and pre-operative assessment of handgrip-strength (HGS). RESULTS: Pre-operative weight loss ≥10% was a significant predictor of mortality at 1 year (OR 2.84, 95%CI 1.03-7.83, p = 0.04) independent of tumour stage, adjuvant treatment, age and gender. Adults prescribed early nutrition support during neoadjuvant treatment experienced less weight loss at 12-months post-oesophagectomy compared to adults prescribed late oral nutrition support (p=<0.05). Pre-operative HGS measurements were not a useful predictor of postoperative complications (p = 0.2), length of stay (p = 0.9) or 90-day mortality (p = 0.6). CONCLUSIONS: Pre-operative weight loss ≥10% was associated with mortality. Early nutrition support was associated with less weight loss at 12-months post-operatively. Pre-operative HGS measures did not have prognostic value as a stand-alone measure. Future work should investigate the efficacy of early nutrition support in reducing both pre- and post-operative weight loss to improve nutritional status and surgical outcomes as part of a multimodal prehabilitation programme in adults with oesophageal cancer.

Standardising clinical outcomes measures for adult clinical trials in Fabry disease: A global Delphi consensus.

BACKGROUND: Recent years have witnessed a considerable increase in clinical trials of new investigational agents for Fabry disease (FD). Several trials investigating different agents are currently in progress; however, lack of standardisation results in challenges to interpretation and comparison. To facilitate the standardisation of investigational programs, we have developed a common framework for future clinical trials in FD. METHODS AND FINDINGS: A broad consensus regarding clinical outcomes and ways to measure them was obtained via the Delphi methodology. 35 FD clinical experts from 4 continents, representing 3389 FD patients, participated in 3 rounds of Delphi procedure. The aim was to reach a consensus regarding clinical trial design, best treatment comparator, clinical outcomes, measurement of those clinical outcomes and inclusion and exclusion criteria. Consensus results of this initiative included: the selection of the adaptative clinical trial as the ideal study design and agalsidase beta as ideal comparator treatment due to its longstanding use in FD. Renal and cardiac outcomes, such as glomerular filtration rate, proteinuria and left ventricular mass index, were prioritised, whereas neurological outcomes including cerebrovascular and white matter lesions were dismissed as a primary or secondary outcome measure. Besides, there was a consensus regarding the importance of patient-related outcomes such as general quality of life, pain, and gastrointestinal symptoms. Also, unity about lysoGb3 and Gb3 tissue deposits as useful surrogate markers of the disease was obtained. The group recognised that cardiac T1 mapping still has potential but requires further development before its widespread introduction in clinical trials. Finally, patients with end-stage renal disease or renal transplant should be excluded unless a particular group for them is created inside the clinical trial. CONCLUSION: This consensus will help to shape the future of clinical trials in FD. We note that the FDA has, coincidentally, recently published draft guidelines on clinical trials in FD and welcome this contribution.

Physio-biochemical, metabolic nitrogen excretion and ion-regulatory assessment in largemouth bass (Micropterus salmoides) following exposure to high environmental iron.

Iron overload is a significant water quality issue in many parts of the world. Therefore, we evaluated the potential toxic effects of waterborne elevated iron on largemouth bass (Micropterus salmoides), a highly valued sport and aquaculture fish species. First, a 96 h-LC50 toxicity assay was performed to understand the tolerance limit of this species to iron; and was determined to be 22.07 mg/L (as Fe3+). Thereafter, to get a better insight on the fish survival during long-term exposure to high environmental iron (HEI) (5.52 mg/L, 25% of the determined 96 h-LC50 value), a suite of physio-biochemical, nitrogenous metabolic and ion-regulatory compensatory responses were examined at 7, 14, 21 and 28 days. Results showed that oxygen consumption dropped significantly at 21 and 28 days of HEI exposure. Ammonia excretion rate (Jamm) was significantly inhibited from day 14 and remained suppressed until the last exposure period. The transcript concentration of Rhesus glycoproteins Rhcg2 declined; likely diminishing ammonia efflux out of gills. These changes were also reflected by a parallel increment in plasma ammonia levels. Under HEI exposure, ion-balance was negatively affected, manifested by reduced plasma [Na+] and parallel inhibition in branchial Na+/K+-ATPase activity. Muscle water content was elevated in HEI-exposed fish, signifying an osmo-regulatory compromise. HEI exposure also increased iron burden in plasma and gills. The iron accumulation pattern in gills was significantly correlated with a suppression of Jamm, branchial Rhcg2 expression and Na+/K+-ATPase activity. There was also a decline in the glycogen, protein and lipid reserves in the hepatic tissue from 14 days, 28 days and 21 days, respectively. Overall, we conclude that sub-lethal chronic iron exposure can impair normal physio-biochemical and ion-regulatory functions in largemouth bass. Moreover, this data set can be applied in assessing the environmental risk posed by a waterborne iron overload on aquatic life.

A qualitative investigation of school age children, their parents and school staff on their participation in the Digital Education to LImit Salt in the Home (DELISH) program.

This study explored the views of participants who completed a 5-week, online, interactive, family-based, salt reduction education program (Digital Education to LImit Salt in the Home). A secondary aim was to explore the views of school staff on the delivery of food and nutrition education in schools. Children aged 7-10 years, their parents and principals/teachers from participating schools located in Victoria, Australia, completed a semi-structured evaluation interview. Audio-recordings of interviews were transcribed verbatim and analysed using NVivo. Twenty-eight interviews (13 children; 11 parents; 4 school staff) were included. Thematic analysis revealed that the program was well received by all groups. Children reported that the interactivity of the education sessions helped them to learn. Parents thought the program was interesting and important, and reported learning skills to reduce salt in the family diet. School staff supported the delivery of nutrition education in schools but indicated difficulties in sourcing well-packed nutrition resources aligned with the curriculum. It appears that there is support from parents and teachers in the delivery of innovative, engaging, nutrition education in schools, however such programs need to be of high quality, aligned with the school curriculum and readily available for incorporation within the school's teaching program.

Why women are not small men: sex-related differences in perioperative cardiopulmonary exercise testing.

BACKGROUND: The use of preoperative cardiopulmonary exercise testing (CPET) to evaluate the risk of adverse perioperative outcomes is increasingly prevalent. CPET-derived information enables personalised perioperative care and enhances shared decision-making. Sex-related differences in physical fitness are reported in non-perioperative literature. However, little attention has been paid to sex-related differences in the context of perioperative CPET. AIM: We explored differences in the physical fitness variables reported in a recently published multi-centre study investigating CPET before colorectal surgery. We also report the inclusion rate of females in published perioperative CPET cohorts that are shaping guidelines and clinical practice. METHODS: We performed a post hoc analysis of the trial data of 703 patients who underwent CPET prior to major elective colorectal surgery. We also summarised the female inclusion rate in peer-reviewed published reports of perioperative CPET. RESULTS: Fitness assessed using commonly used perioperative CPET variables-oxygen consumption at anaerobic threshold (AT) and peak exercise-was significantly higher in males than in females both before and after correction for body weight. In studies contributing to the development of perioperative CPET, 68.5% of the participants were male. CONCLUSION: To our knowledge, this is the first study to describe differences between males and females in CPET variables used in a perioperative setting. Furthermore, there is a substantial difference between the inclusion rates of males and females in this field. These findings require validation in larger cohorts and may have significant implications for both sexes in the application of CPET in the perioperative setting.

Oxidative stress, histopathological alterations and anti-oxidant capacity in different tissues of largemouth bass (Micropterus salmoides) exposed to a newly developed sodium carbonate peroxyhydrate granular algaecide formulated with hydrogen peroxide.

Various strategies exist to control noxious cyanobacterial populations, although the application of a newly developed granular compound (sodium carbonate peroxyhydrate 'SCP', trade name 'PAK® 27' algaecide) containing hydrogen peroxide (H2O2) as the active ingredient, has been recently proven as an effective and ecofriendly treatment. However, in aquaculture settings the application of SCP to treat cynobacterial blooms may affect non-targeted biota, such as fish due to H2O2 being known to elicit toxic oxidative stress. Consequently, a better understanding of the side effects as a function of dosing concentrations would help to improve treatment efficacy and fish welfare. Thus, the aim of the current study is to assess the potential risks of SCP to largemouth bass (Micropterus salmoides), a high priced fish in the U.S. To this end, fish were exposed to two recommended doses of SCP corresponding to either 2.5 or 4.0 mg/L H2O2 for 6 days, with a control group in parallel. After 6 days, the effect of SCP exposure on oxidative stress, histopathological changes and anti-oxidant potential in the brain, liver, gills and muscle were investigated. Results show that exposure to 4.0 mg/L H2O2 -SCP incited oxidative damage, evidenced by an over-accumulation of H2O2 and malondialdehyde (MDA) in the brain and liver, which were accompanied by an increment in xanthine oxidase activity. Unlike 4.0 mg/L H2O2, these oxidative stress biomarkers in the brain and liver tissue of 2.5 mg/L H2O2-SCP exposed fish were restrained within control levels and concomitant with an increase in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione-s-transferase (GST) activity. In contrast, many of these anti-oxidants sentinels in the 4.0 mg/L H2O2 exposed fish were either unaffected or significantly inhibited, which resulted in over-accumulation of H2O2 and MDA. In addition, a series of histopathological alterations were observed, and the most severe brain injuries and liver inflammation were recorded in 4.0 mg/L H2O2-SCP exposed fish. Based on oxidative parameters, both SCP doses resulted in a relatively mild oxidative stress in gills but no effect in muscle, probably explaining the modest anti-oxidative responses in the former and almost complete lack of anti-oxidative responses in the latter. Overall, our findings suggests that the application of SCP at 4.0 mg/L H2O2 to control cyanobacterial blooms in aquaculture settings can possess potential risks to the farmed fish.

Biomass of the Cyanobacterium Lyngbya wollei Alters Copper Algaecide Exposure and Risks to a Non-target Organism.

Nuisance algal infestations are increasing globally in distribution and frequency. Copper-based algaecides are routinely applied to control these infestations, though there is an ever-present concern of risks to non-target species. This research evaluated risks associated with a commonly applied chelated copper algaecide (Captain® XTR; SePRO Corporation) to a sentinel non-target species (Daphnia magna) and further assessed alteration of the exposure and toxicity when a nuisance mat-forming cyanobacterium, Lyngbya wollei, was present in exposures. Aqueous copper concentrations in treatments with algae significantly decreased within 1 h after treatment and averaged 57.5% of nominal amended Cu through the experiment duration. The 48 h LC50 values were 371 µg Cu/L with no algae present in exposures and increased significantly to 531 µg Cu/L when L. wollei was simultaneously exposed. This research provides information on the short-term fate of copper and hazard assessment by incorporating targeted binding ligands, as present in operational treatments.

Exercise prehabilitation may lead to augmented tumor regression following neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

  Purpose: We evaluate the effect of an exercised prehabilitation programme on tumour response in rectal cancer patients following neoadjuvant chemoradiotherapy (NACRT). Patients and Methods: Rectal cancer patients with (MRI-defined) threatened resection margins who completed standardized NACRT were prospectively studied in a post hoc, explorative analysis of two previously reported clinical trials. MRI was performed at Weeks 9 and 14 post-NACRT, with surgery at Week 15. Patients undertook a 6-week preoperative exercise-training programme. Oxygen uptake (VO2) at anaerobic threshold (AT) wasmeasured at baseline (pre-NACRT), after completion of NACRT and at week 6 (post-NACRT). Tumour related outcome variables: MRI tumour regression grading (ymrTRG) at Week 9 and 14; histopathological T-stage (ypT); and tumour regression grading (ypTRG)) were compared. Results: 35 patients (26 males) were recruited. 26 patients undertook tailored exercise-training with 9 unmatched controls. NACRT resulted in a fall in VO2 at AT -2.0 ml/kg-1/min-1(-1.3,-2.6), p < 0.001. Exercise was shown to reverse this effect. VO2 at AT increased between groups, (post-NACRT vs. week 6) by +1.9 ml/kg-1/min-1(0.6, 3.2), p = 0.007. A significantly greater ypTRG in the exercise group at the time of surgery was found (p = 0.02). Conclusion: Following completion of NACRT, exercise resulted in significant improvements in fitness and augmented pathological tumour regression.

Exact Variance-Reduced Simulation of Lattice Continuous-Time Markov Chains with Applications in Reaction Networks.

We propose an algorithm to reduce the variance of Monte Carlo simulation for the class of countable-state, continuous-time Markov chains, or lattice CTMCs. This broad class of systems includes all processes that can be represented using a random-time-change representation, in particular reaction networks. Numerical studies demonstrate order-of-magnitude reduction in MSE for Monte Carlo mean estimates using our approach for both linear and nonlinear systems. The algorithm works by simulating pairs of negatively correlated, identically distributed sample trajectories of the stochastic process and using them to produce variance-reduced, unbiased Monte Carlo estimates, effectively generalizing the method of antithetic variates into the domain of stochastic processes. We define a method to simulate anticorrelated, unit-rate Poisson process paths. We then show how these antithetic Poisson process pairs can be used as the input for random time-change representations of any lattice CTMC, in order to produce anticorrelated trajectories of the desired process. We present three numerical parameter studies. The first examines the algorithm's performance for the unit-rate Poisson process, and the next two demonstrate the effectiveness of the algorithm in simulating reaction network systems: a gene expression system with affine rate functions and an aerosol particle coagulation system with nonlinear rates. We also prove exact, analytical expressions for the time-resolved and integrated covariance between our antithetic Poisson processes for one technique.

Causes of volcanic unrest at Mt. Spurr in 2004-2005 inferred from repeated tomography.

Mt. Spurr is the largest active volcano in Alaska of high explosive potential. The most recent activity, including two recent magmatic eruptions in 1953 and 1992, has occurred via the flanking Crater Peak. From 2004 to 2006, strong seismicity, gas flux, and heating were observed in the summit area, which had remained inactive for more than 5 Ka. To understand the cause of this reactivation, we performed repeated tomography inversions that clearly imaged the magma reservoir beneath Mt. Spurr and showed temporal changes in its shape and intensity. During the two years preceding the unrest, we observed ascension of the upper limit of the reservoir-related anomaly from a depth of 5 to 3 km below the surface, accompanied by strong seismicity. During the following years, the shape of the anomaly remained unchanged, but its intensity weakened. These observations may indicate the release of fluids from the ductile reservoir and fast upward ascent through the brittle cover that caused intensive seismicity and gas flux during the unrest from 2004 to 2006. The origin of this zone will possibly cause a resumption of explosive eruptions in the summit area of Mt. Spurr.

A systematic review of the safety and efficacy of aerobic exercise during cytotoxic chemotherapy treatment.

PURPOSE: Aerobic exercise improves prognosis and quality of life (QoL) following completion of chemotherapy. However, the safety and efficacy of aerobic exercise during chemotherapy is less certain. A systematic review was performed of randomised trials of adult patients undergoing chemotherapy, comparing an exercise intervention with standard care. METHOD: From 253 abstracts screened, 33 unique trials were appraised in accordance with PRISMA guidance, including 3257 patients. Interventions included walking, jogging or cycling, and 23 were of moderate intensity (50-80% maximum heart rate). RESULTS: Aerobic exercise improved, or at least maintained fitness during chemotherapy. Moderately intense exercise, up to 70-80% of maximum heart rate, was safe. Any reported adverse effects of exercise were mild and self-limiting, but reporting was inconsistent. Adherence was good (median 72%). Exercise improved QoL and physical functioning, with earlier return to work. Two out of four studies reported improved chemotherapy completion rates. Four out of six studies reported reduced chemotherapy toxicity. There was no evidence that exercise reduced myelosuppression or improved response rate or survival. CONCLUSIONS: Exercise during chemotherapy is safe and should be encouraged because of beneficial effects on QoL and physical functioning. More research is required to determine the impact on chemotherapy completion rates and prognosis.

The presence of algae mitigates the toxicity of copper-based algaecides to a nontarget organism.

Copper-based algaecides are routinely applied to target noxious algal blooms in freshwaters. Standard toxicity testing data with copper suggest that typical concentrations used to control algae can cause deleterious acute impacts to nontarget organisms. These "clean" water experiments lack algae, which are specifically targeted in field applications of algaecides and contain competing ligands. The present research measured the influence of algae on algaecide exposure and subsequent response of the nontarget species Daphnia magna to copper sulfate and an ethanolamine-chelated copper algaecide (Captain®). Significant shifts (p < 0.05) in D. magna 48-h median lethal concentration (LC50) values were found when algae were present in exposures along with a copper salt or a chelated copper formulation. Copper sulfate 48-h LC50 values shifted from 75.3 to 317.8 and 517.8 µg Cu/L, whereas Captain increased from 353.8 to 414.2 and 588.5 µg Cu/L in no algae, 5 × 105 , and 5 × 106 cells/mL algae treatments, respectively. Larger shifts were measured with copper sulfate exposures, although Captain was less toxic to D. magna in all corresponding treatments. Captain was more effective at controlling Scenedesmus dimorphus at most concentrations, and control was inversely proportional to toxicity to D. magna. Overall, incorporating target competing ligands (i.e., algae) into standard toxicity testing is important for accurate risk assessment, and copper formulation can significantly alter algaecidal efficacy and risks to nontarget organisms. Environ Toxicol Chem 2018;37:2132-2142. © 2018 SETAC.