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38 result(s) for "McIntosh, Kyle"
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Spatial and Temporal Variability of Saxitoxin-Producing Cyanobacteria in U.S. Urban Lakes
Harmful cyanobacterial blooms (HCBs) are of growing global concern due to their production of toxic compounds, which threaten ecosystems and human health. Saxitoxins (STXs), commonly known as paralytic shellfish poison, are a neurotoxic alkaloid produced by some cyanobacteria. Although many field studies indicate a widespread distribution of STX, it is understudied relative to other cyanotoxins such as microcystins (MCs). In this study, we assessed eleven U.S. urban lakes using qPCR, sxtA gene-targeting sequencing, and 16S rRNA gene sequencing to understand the spatio-temporal variations in cyanobacteria and their potential role in STX production. During the blooms, qPCR analysis confirmed the presence of the STX-encoding gene sxtA at all lakes. In particular, the abundance of the sxtA gene had a strong positive correlation with STX concentrations in Big 11 Lake in Kansas City, which was also the site with the highest quantified STX concentration. Sequencing analysis revealed that potential STX producers, such as Aphanizomenon, Dolichospermum, and Raphidiopsis, were present. Further analysis targeting amplicons of the sxtA gene identified that Aphanizomenon and/or Dolichospermum are the primary STX producer, showing a significant correlation with sxtA gene abundances and STX concentrations. In addition, Aphanizomenon was associated with environmental factors, such as conductivity, sulfate, and orthophosphate, whereas Dolichospermum was correlated with temperature and pH. Overall, the results herein enhance our understanding of the STX-producing cyanobacteria and aid in developing strategies to control HCBs.
Genomic Characterization and Wetland Occurrence of a Novel Campylobacter Isolate from Canada Geese
Populations of resident, non-migratory Canada geese are rapidly increasing. Canada geese are known to transmit viral and bacterial diseases, posing a possible threat to human health. The most prevalent pathogens vectored by geese are Campylobacter species, yet the current understanding of the identity and virulence of these pathogens is limited. In our previous study, we observed a high prevalence of Campylobacter spp. in the Banklick Creek wetland—a constructed treatment wetland (CTW) located in northern KY (USA) used to understand sources of fecal contamination originating from humans and waterfowl frequenting the area. To identify the types of Campylobacter spp. found contaminating the CTW, we performed genetic analyses of Campylobacter 16s ribosomal RNA amplified from CTW water samples and collected fecal material from birds frequenting those areas. Our results showed a high occurrence of a Campylobacter canadensis-like clade from the sampling sites. Whole-genome sequence analyses of an isolate from Canada goose fecal material, called MG1, were used to confirm the identity of the CTW isolates. Further, we examined the phylogenomic position, virulence gene content, and antimicrobial resistance gene profile of MG1. Lastly, we developed an MG1-specific real-time PCR assay and confirmed the presence of MG1 in Canada goose fecal samples surrounding the CTW. Our findings reveal that the Canada goose-vectored Campylobacter sp. MG1 is a novel isolate compared to C. canadensis that possesses possible zoonotic potential, which may be of human health concern.
A Novel Dialkylamino-Functionalized Chalcone, DML6, Inhibits Cervical Cancer Cell Proliferation, In Vitro, via Induction of Oxidative Stress, Intrinsic Apoptosis and Mitotic Catastrophe
In this study, we designed, synthesized and evaluated, in vitro, novel chalcone analogs containing dialkylamino pharmacophores in the cervical cancer cell line, OV2008. The compound, DML6 was selective and significantly decreased the proliferation of OV2008 and HeLa cells in sub-micromolar concentrations, compared to prostate, lung, colon, breast or human embryonic kidney cell line (HEK293). DML6, at 5 μM, arrested the OV2008 cells in the G2 phase. Furthermore, DML6, at 5 μM, increased the levels of reactive oxygen species and induced a collapse in the mitochondrial membrane potential, compared to OV2008 cells incubated with a vehicle. DML6, at 5 μM, induced intrinsic apoptosis by significantly (1) increasing the levels of the pro-apoptotic proteins, Bak and Bax, and (2) decreasing the levels of l the anti-apoptotic protein, Bcl-2, compared to cell incubated with a vehicle. Furthermore, DML6, at 5 and 20 μM, induced the cleavage of caspase-9, followed by subsequent cleavage of the executioner caspases, caspase-3 and caspase-7, which produced OV2008 cell death. Overall, our data suggest that DML6 is an apoptosis-inducing compound that should undergo further evaluation as a potential treatment for cervical cancer.
Estimation of impulse response between electromyogram signals for use in conduction delay distribution estimation
The time delay between two surface electromyograms (EMGs) acquired along the conduction path is used to estimate mean action potential conduction velocity. Modeling the linear impulse response between “upstream” and “downstream” EMG signals permits an estimate of the distribution of velocities, providing more information. In this work, we analyzed EMG from bipolar electrodes placed on the tibialis anterior of 36 subjects, using an inter-electrode distance of 10 mm. Regularized least squares was used to fit the coefficients of a finite impulse response model. We trained the model on one recording, then tested on two others. The optimum correlation between the model-predicted and actual EMG averaged 0.70. We also compared estimation of the mean conduction delay from the peak time of the impulse response to the “gold standard” peak time of the cross-correlation between the upstream and downstream EMG signals. Optimal models differed from the gold standard by 0.02 ms, on average. Model performance was influenced by the regularization parameters. The impulse responses, however, incorrectly contained substantive power at very low time delays, causing delay distribution estimates to exhibit high probabilities at very short conduction delays. Unrealistic distribution estimates resulted. Larger inter-electrode spacing may be required to alleviate this limitation.
Alkenones as a Promising Green Alternative for Waxes in Cosmetics and Personal Care Products
The move toward green, sustainable, natural products has been growing in the cosmetic and personal care industry. Ingredients derived from marine organisms and algae are present in many cosmetic products. In this study, a new green ingredient, a wax (i.e., long-chain alkenones) derived from Isochyrsis sp., was evaluated as an alternative for cosmetic waxes. First, the melting point was determined (71.1–77.4 °C), then the alkenones’ thickening capability in five emollients was evaluated and compared to microcrystalline wax and ozokerite. Alkenones were compatible with three emollients and thickened the emollients similarly to the other waxes. Then, lipsticks and lip balms were formulated with and without alkenones. All products remained stable at room temperature for 10 weeks. Lipstick formulated with alkenones was the most resistant to high temperature. Finally, alkenones were compared to three cosmetic thickening waxes in creams. Viscosity, rheology, and stability of the creams were evaluated. All creams had a gel-like behavior. Both viscosity and storage modulus increased in the same order: cream with alkenones < cetyl alcohol < stearic acid < glyceryl monostearate. Overall, alkenones’ performance was comparable to the other three waxes. Alkenones can thus offer a potential green choice as a new cosmetic structuring agent.
Neural, biomechanical, and physiological factors involved in sex-related differences in the maximal rate of isometric torque development
Objective Recent research has reported that lower maximal rate of torque development (dτ/d t max ) exhibited by females, relative to males, during knee extension can be accounted for by normalization to a maximal voluntary contraction (MVC); however, this was not seen in the upper limb. Purpose The aim of the current work was to examine the contribution of maximum strength (τ max ), twitch contraction time (CT), muscle fiber condition velocity (MFCV), and rate of muscle activation (Q 30 ) to sex-differences in the dτ/d t max during maximal isometric dorsiflexion. Methods Thirty-eight participants (20 males; 18 females) performed both maximal voluntary and evoked isometric contractions of the tibialis anterior across 3 days. Ten maximal compound muscle action potentials were elicited and subsequently followed by three, 5-s contractions. From the recordings, MFCV, dτ/d t max , τ max , CT, electromechanical delay (EMD), root-mean squared (RMS) amplitude, peak-to-peak voltage (Vpp), and Q 30 were calculated. Results An ANCOVA showed that τ max accounted for all the sex-differences in dτ/d t max ( p  = 0.96). There were no significant differences between groups with respect to MFCV, RMS amplitude, Vpp amplitude, or CT. However, there was a significant sex-difference in dτ/d t max , τ max , and Q 30 . Females had longer evoked EMD times compared with males (15.69 ± 10.57 ms versus 9.95 ± 3.46 ms; p  = 0.01), but the voluntary EMD times were not different. Conclusion The current research supports the work by Hannah et al. Exp Physiol 97:618–629, ( 2012 ) that normalization to MVC in the quadriceps is able to account for all sex-differences in rate of toque development in the lower limb.
Pharmaceutical Applications and Toxicity of Extracted Alkenones from Marine Isochrysis Algae
Isochrysis is a commercially available marine algae used for animal feed, human nutrient supplements, and biodiesel. The Isochrysis galbana species is one of four genera of haptophytes that produces unique, long-chain lipids known as alkenones. However, there is a lack of physical characteristics and toxicity data for alkenones in animals, thus, limiting their use in humans. In the first aim of this study, alkenones derived from Isochrysis sp. were evaluated for their chemical structure characteristics as an alternative for waxes used in personal care products. The melting point of the alkenone was determined (71.1–77.4°C), and their thickening capability in five emollients was evaluated and compared to microcrystalline wax and ozokerite. Alkenones showed compatibility with three emollients, isopropyl isostearate, C12-C15 alkyl benzoate, and ethylhexyl methyxycinnamate, and they thickened the emollients similar to the other tested waxes. Lipsticks and lip balms were formulated with and without alkenones. All products remained stable at room temperature for 10 weeks. Lipstick formulated with alkenones was the most resistant to high temperature. Finally, alkenones were compared to three cosmetic thickening waxes in creams. Viscosity, rheology and stability of the creams were evaluated. All creams had a gel-like behavior. Overall, the alkenones in these formulas were comparable to the other three waxes. Thus, alkenones can offer a potential green choice as a new personal care structuring compound.For the second aim of this study, we performed acute oral, acute dermal and repeated 28-day dermal toxicity studies using female SAS (an acronym for the company SASCO where the colony was bred) Sprague Dawley rats. Our behavioral studies (level of grooming, eye opening, walking, exploring, body posture, breathing, scratching, and nose flattening) indicated that the specific alkenones had no visible behavioral effects at oral doses up to 4000 mg/kg. In addition, there were no significant changes in food consumption or body weight, and there was no significant histopathological changes in the liver, kidneys, spleen, heart or skin compared to animals treated with vehicle. In the acute and chronic dermal toxicity studies, the alkenones produced less irritation and did not significantly damage the skin based on the Draize skin reaction scale and transepidermal water loss readings compared to the positive control, 1% sodium lauryl sulfate. Overall, our results indicated that alkenones are safe in female Sprague Dawley rats, suggesting that they could be used for both oral and dermal formulations, although additional studies would be required before these alkenones could be applied to human personal care products.
Genomic Characterization and Wetland Occurrence of a Novel ICampylobacter/I Isolate from Canada Geese
Populations of resident, non-migratory Canada geese are rapidly increasing. Canada geese are known to transmit viral and bacterial diseases, posing a possible threat to human health. The most prevalent pathogens vectored by geese are Campylobacter species, yet the current understanding of the identity and virulence of these pathogens is limited. In our previous study, we observed a high prevalence of Campylobacter spp. in the Banklick Creek wetland—a constructed treatment wetland (CTW) located in northern KY (USA) used to understand sources of fecal contamination originating from humans and waterfowl frequenting the area. To identify the types of Campylobacter spp. found contaminating the CTW, we performed genetic analyses of Campylobacter 16s ribosomal RNA amplified from CTW water samples and collected fecal material from birds frequenting those areas. Our results showed a high occurrence of a Campylobacter canadensis-like clade from the sampling sites. Whole-genome sequence analyses of an isolate from Canada goose fecal material, called MG1, were used to confirm the identity of the CTW isolates. Further, we examined the phylogenomic position, virulence gene content, and antimicrobial resistance gene profile of MG1. Lastly, we developed an MG1-specific real-time PCR assay and confirmed the presence of MG1 in Canada goose fecal samples surrounding the CTW. Our findings reveal that the Canada goose-vectored Campylobacter sp. MG1 is a novel isolate compared to C. canadensis that possesses possible zoonotic potential, which may be of human health concern.
A quality improvement initiative to improve adherence to national guidelines for empiric management of community-acquired pneumonia in emergency departments
Objective. The objective of this study was to improve the concordance of community-acquired pneumonia management in Australian emergency departments with national guidelines through a quality improvement initiative promoting concordant antibiotic use and use of a pneumonia severity assessment tool, the pneumonia severity index (PSI). Design and Interventions. Drug use evaluation, a quality improvement methodology involving data collection, evaluation, feedback and education, was undertaken. Educational interventions included academic detailing, group feedback presentations and prescribing prompts. Setting and Participants. Data were collected on 20 consecutive adult community-acquired pneumonia emergency department presentations by each hospital for each of three audits. Main Outcome Measures. Two process indicators measured the impact of the interventions: documented PSI use and concordance of antibiotic prescribing with guidelines. Comparisons were performed using a Chi-squared test. Results. Thirty-seven hospitals, including public, private, rural and metropolitan institutions, participated. Twenty-six hospitals completed the full study (range: 462—518 patients), incorporating two intervention phases and subsequent follow-up audits. The baseline audit of community-acquired pneumonia management demonstrated that practice was varied and mostly discordant with guidelines. Documented PSI use subsequently improved from 30/518 (6%, 95% confidence interval [CI] 4-8) at baseline to 125/503 (25%, 95% CI 21-29; P < 0.0001) and 102/462 (22%, 95% CI 18-26; P< 0.0001) in audits two and three, respectively, while concordant antibiotic prescribing improved from 101/518 (20%, 95% CI 16-23) to 132/462 (30%, 95% CI 26-34; P< 0.0001) and 132/462 (29%, 95% CI 24-33; P< 0.001), respectively. Conclusions. Improved uptake of guideline recommendations for community-acquired pneumonia management in emergency departments was documented following a multi-faceted education intervention.
The Role of Antioxidant Enzymes in the Induction of Phagocytic Activation by Dichloroacetate and Trichloroacetate Mixtures in Mice
The process of water chlorination results in production of different disinfection byproducts (DBPs), including dichloroacetate (DCA) and trichloroacetate (TCA). The compounds have been found to be hepatotoxic and hepatocarcinogenic in rodents. Previous studies have indicated the roles of oxidative stress (OS) and phagocytic activations in the induction of these effects in B6C3F1 mice. Also, previous studies have reported effects of DCA and TCA mixtures that ranged from additive to greater than additive on the induction of hepatic OS and additive to less than additive on the induction of phagocytic activation in mice. In this study, frozen peritoneal lavage cells collected from mice treated for those previous studies were used. In those studies, groups of mice were administered 7.5, 15, 30 mg/kg/day of DCA, 12.5, 25, 50 mg/kg/day of TCA, and 3 different mixtures of the compounds (Mix I, Mix II and Mix III) post orally for 13 weeks. The DCA: TCA ratios in Mix I, Mix II, Mix III corresponded to 7.5:12.5, 15:25, 30:50 mg/kg/day, respectively. Mice were then sacrificed and the peritoneal lavage cells (PLCs) were isolated and kept frozen at -80 C. Cells were assayed for the activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as for the amount of glutathione (GSH). DCA, TCA and mixtures administration resulted in dose-dependent increases in SOD activity. Also, DCA, TCA, and mixture I treatments resulted in no change in CAT or GSH-Px activities while Mix II and Mix III resulted in significant increases in those enzyme activities. While 50 mg/kg/day TCA, and Mix I and Mix. II resulted in significant increases in total GSH levels; the rest of the other treatments did not result in significant changes in the levels of that biomarker. Failure of phagocytic activation has been previously suggested to contribute to increases in the hepatotoxic/ hepatocarcinogenic effects of DCA and TCA, and mixtures of high concentrations. The results of this study suggest that antioxidant enzymes and GSH play significant roles, in controlling the process of phagocytic activation, and that it significantly contributes to failure of this process to respond to high mixture concentrations.