The Behavioral Cost of Care: Changes in Maintenance Behavior during Equine-Assisted Interventions.

This study examined human-animal symbiosis in an animal-assisted intervention through observations of animal maintenance behaviors. The rise of psychotherapy, learning, and recreation incorporating animals warrants exploration of the welfare of the animals involved in these interventions. The analysis of welfare in multispecies engagements can be discussed in terms of symbiosis. Regarding an intervention's animal provider (e.g., therapy horse) and human recipient (psychotherapy client), the balance of cost and benefit is important. Research describing human and animal interactive behavior during interventions is limited, whether focusing on client outcomes or animal welfare. The present study adapted ethological methods to study humans and animals in an equine-assisted intervention, observing equine maintenance behaviors and equid-human interactive behavior. Maintenance behaviors were recorded before, during, and after equine-assisted (psychosocial) learning sessions with youth, providing 1600 observations. Equine alertness, eating behavior, and ambulation varied significantly before, during, and after the equine-assisted sessions. Such interruptions of typical behavior are an important aspect of welfare and unit of analysis when examining symbiotic relationships. A total of 267 sequences of equid-human approach-response behavior were also recorded, indicating that human-animal interaction was predominantly from humans toward equids. Equids' dominant response to human approach was no response, followed by avoidance, while humans' dominant response to equid approach was reciprocation. The findings are discussed in terms of symbiosis and animal welfare.

A novel treatment strategy to prevent Parkinson's disease: focus on iron regulatory protein 1 (IRP1).

We propose that neural damage in Parkinson's disease (PD) is due to dysregulation of iron utilization rather than to high iron levels per se. Iron deposits are associated with neuronal cell death in substantia nigra (SN) resulting in PD where high levels of iron in SNs are due to dysregulation of iron utilization. Cytosolic aconitase (ACO1) upon losing an iron-sulfur cluster becomes iron regulatory protein 1 (IRP1). Rotenone increases levels of IRP1 and induces PD in rats. An increase in iron leads to inactivation of IRP1. We propose a novel treatment strategy to prevent PD. Specifically in rats given rotenone by subcutaneous injections, iron, from iron carbonyl from which iron is slowly absorbed, given three times a day by gavage will keep iron levels constant in the gut whereby iron levels and iron utilization systematically can be tightly regulated. Rotenone adversely affects complex 1 iron-sulfur proteins. Iron supplementation will increase iron-sulfur cluster formation switching IRP1 to ACO1. With IRP1 levels kept constantly low, iron utilization will systematically be tightly regulated stopping dysregulation of complex 1 and the neural damage done by rotenone preventing PD.

Activation analysis and evaluation of the radionuclide inventories, decay heat for European DEMO divertor components.

This work presents neutron flux calculation results and specific decay heat and activity for the European DEMO reactor divertor structure. Two DEMO 2017 models were used in calculations; one with a homogenised WCLL breeder blanket and the other with a homogenised HCPB breeder blanket. The neutron flux calculations were performed using MCNP6 code with JEFF 3.2 nuclear data. Activation and decay heat calculations were performed using the FISPACT-II code with TENDL - 2017 nuclear data library.

Bernstein Polynomial-Based Method for Solving Optimal Trajectory Generation Problems.

This paper presents a method for the generation of trajectories for autonomous system operations. The proposed method is based on the use of Bernstein polynomial approximations to transcribe infinite dimensional optimization problems into nonlinear programming problems. These, in turn, can be solved using off-the-shelf optimization solvers. The main motivation for this approach is that Bernstein polynomials possess favorable geometric properties and yield computationally efficient algorithms that enable a trajectory planner to efficiently evaluate and enforce constraints along the vehicles' trajectories, including maximum speed and angular rates as well as minimum distance between trajectories and between the vehicles and obstacles. By virtue of these properties and algorithms, feasibility and safety constraints typically imposed on autonomous vehicle operations can be enforced and guaranteed independently of the order of the polynomials. To support the use of the proposed method we introduce BeBOT (Bernstein/Bézier Optimal Trajectories), an open-source toolbox that implements the operations and algorithms for Bernstein polynomials. We show that BeBOT can be used to efficiently generate feasible and collision-free trajectories for single and multiple vehicles, and can be deployed for real-time safety critical applications in complex environments.

Osteoporosis and the effect of dysregulation of the transsulfuration pathway via taurine on intracellular calcium homeostasis, vitamin D absorption and vitamin K absorption.

BACKGROUND & AIMS: In this article we connect the dysregulation of the transsulfuration pathway to bone dysregulations and propose a novel treatment for osteoporosis. Current treatments for osteoporosis are very frequently inadequate. In osteoporosis, the risk of fractures increases with increased homocysteine (Hcy). METHODS: Here, we conduct a review on the relationship between osteoporosis and the dysregulation of the transsulfuration pathway. RESULTS: we show that the transsulfuration pathway metabolizes Hcy to L-cysteine. Increased Hcy levels point to the transsulfuration pathway being dysregulated. With the transsulfuration pathway dysregulated, there will be decreased levels of L-cysteine and decreased levels of taurine, which is synthesized from L-cysteine. Taurine levels are decreased in patients with osteoporosis. Taurine regulates intracellular calcium homeostasis. Taurine, also, when conjugated with bile acids assists with absorption of fats and fat-soluble vitamins such as vitamin D and vitamin K. Dysregulated calcium homeostasis, decreased calcium absorption and decreased absorption of vitamin D and vitamin K due to low levels of taurine negatively affect bone mineral density (BMD) leading to osteoporosis and fractures. CONCLUSIONS: In this article, we propose that a combination of taurine, calcium, vitamin D and vitamin K, could increase BMD reducing number of years spent in disability and reducing deaths due to fractures in patients with osteoporosis.

A disease-modifying treatment for Alzheimer's disease: focus on the trans-sulfuration pathway.

High homocysteine levels in Alzheimer's disease (AD) result from low activity of the trans-sulfuration pathway. Glutathione levels are also low in AD. L-cysteine is required for the synthesis of glutathione. The synthesis of coenzyme A (CoA) requires L-cysteine, which is synthesized via the trans-sulfuration pathway. CoA is required for the synthesis of acetylcholine and appropriate cholinergic neurotransmission. L-cysteine is required for the synthesis of molybdenum-containing proteins. Sulfite oxidase (SUOX), which is a molybdenum-containing protein, could be dysregulated in AD. SUOX detoxifies the sulfites. Glutaminergic neurotransmission could be dysregulated in AD due to low levels of SUOX and high levels of sulfites. L-cysteine provides sulfur for iron-sulfur clusters. Oxidative phosphorylation (OXPHOS) is heavily dependent on iron-sulfur proteins. The decrease in OXPHOS seen in AD could be due to dysregulations of the trans-sulfuration pathway. There is a decrease in aconitase 1 (ACO1) in AD. ACO1 is an iron-sulfur enzyme in the citric acid cycle that upon loss of an iron-sulfur cluster converts to iron regulatory protein 1 (IRP1). With the dysregulation of iron-sulfur cluster formation ACO1 will convert to IRP1 which will decrease the 2-oxglutarate synthesis dysregulating the citric acid cycle and also dysregulating iron metabolism. Selenomethionine is also metabolized by the trans-sulfuration pathway. With the low activity of the trans-sulfuration pathway in AD selenoproteins will be dysregulated in AD. Dysregulation of selenoproteins could lead to oxidant stress in AD. In this article, we propose a novel treatment for AD that addresses dysregulations resulting from low activity of the trans-sulfuration pathway and low L-cysteine.

Treatment-resistant schizophrenia: focus on the transsulfuration pathway.

Treatment-resistant schizophrenia (TRS) is a severe form of schizophrenia. The severity of illness is positively related to homocysteine levels, with high homocysteine levels due to the low activity of the transsulfuration pathway, which metabolizes homocysteine in synthesizing L-cysteine. Glutathione levels are low in schizophrenia, which indicates shortages of L-cysteine and low activity of the transsulfuration pathway. Hydrogen sulfide (H2S) levels are low in schizophrenia. H2S is synthesized by cystathionine ß-synthase and cystathionine γ-lyase, which are the two enzymes in the transsulfuration pathway. Iron-sulfur proteins obtain sulfur from L-cysteine. The oxidative phosphorylation (OXPHOS) pathway has various iron-sulfur proteins. With low levels of L-cysteine, iron-sulfur cluster formation will be dysregulated leading to deficits in OXPHOS in schizophrenia. Molybdenum cofactor (MoCo) synthesis requires sulfur, which is obtained from L-cysteine. With low levels of MoCo synthesis, molybdenum-dependent sulfite oxidase (SUOX) will not be synthesized at appropriate levels. SUOX detoxifies sulfite from sulfur-containing amino acids. If sulfites are not detoxified, there can be sulfite toxicity. The transsulfuration pathway metabolizes selenomethionine, whereby selenium from selenomethionine can be used for selenoprotein synthesis. The low activity of the transsulfuration pathway decreases selenoprotein synthesis. Glutathione peroxidase (GPX), with various GPXs being selenoprotein, is low in schizophrenia. The dysregulations of selenoproteins would lead to oxidant stress, which would increase the methylation of genes and histones leading to epigenetic changes in TRS. An add-on treatment to mainline antipsychotics is proposed for TRS that targets the dysregulations of the transsulfuration pathway and the dysregulations of other pathways stemming from the transsulfuration pathway being dysregulated.

The Use of Tethered Bilayer Lipid Membranes to Identify the Mechanisms of Antimicrobial Peptide Interactions with Lipid Bilayers.

This review identifies the ways in which tethered bilayer lipid membranes (tBLMs) can be used for the identification of the actions of antimicrobials against lipid bilayers. Much of the new research in this area has originated, or included researchers from, the southern hemisphere, Australia and New Zealand in particular. More and more, tBLMs are replacing liposome release assays, black lipid membranes and patch-clamp electrophysiological techniques because they use fewer reagents, are able to obtain results far more quickly and can provide a uniformity of responses with fewer artefacts. In this work, we describe how tBLM technology can and has been used to identify the actions of numerous antimicrobial agents.

Lipid Membrane Interactions of the Cationic Antimicrobial Peptide Chimeras Melimine and Cys-Melimine.

Melimine and its derivatives are synthetic chimeric antimicrobial agents based on protamine and melittin. The binding of solubilized melimine and its derivative, with a cysteine on N-terminus, (cys-melimine) on tethered bilayer lipid membranes (tBLMs) was examined using ac electrical impedance spectroscopy. The addition of melimine and cys-melimine initially increased membrane conduction, which subsequently falls over time. The results were obtained for tBLMs comprising zwitterionic phosphatidylcholine, anionic phosphatidylglycerol, or tBLMs made using purified lipids from Escherichia coli. The effect on conduction is more marked with the cysteine variant than the noncysteine variant. The variation in membrane conduction most probably arises from individual melimines inducing increased ionic permeability, which is then reduced as the melimines aggregate and phase-separate within the membrane. The actions of these antimicrobials are modeled in terms of altering the critical packing parameter (CPP) of the membranes. The variations in the peptide length of cys-melimine were compared with a truncated version of the peptide, cys-mel4. The results suggest that the smaller molecule impacts the membrane by a mechanism that increases the average CPP, reducing membrane conduction. Alternatively, an uncharged alanine-replacement version of melimine still produced an increase in membrane conduction, further supporting the CPP model of geometry-induced toroidal pore alterations. All the data were then compared to their antimicrobial effectiveness for the Gram-positive and Gram-negative strains of bacteria, and their fusogenic properties were examined using dynamic light scattering in 1-oleoyl-2-hydroxy- sn-glycero-3-phosphocholine lipid spheroids. We conclude that a degree of correlation exists between the antimicrobial effectiveness of the peptides studied here and their modulation of membrane conductivity.

Design and synthesis of short amphiphilic cationic peptidomimetics based on biphenyl backbone as antibacterial agents.

Antimicrobial peptides (AMPs) and their synthetic mimics have received recent interest as new alternatives to traditional antibiotics in attempts to overcome the rise of antibiotic resistance in many microbes. AMPs are part of the natural defenses of most living organisms and they also have a unique mechanism of action against bacteria. Herein, a new series of short amphiphilic cationic peptidomimetics were synthesized by incorporating the 3'-amino-[1,1'-biphenyl]-3-carboxylic acid backbone to mimic the essential properties of natural AMPs. By altering hydrophobicity and charge, we identified the most potent analogue 25g that was active against both Gram-positive Staphylococcus aureus (MIC = 15.6 µM) and Gram-negative Escherichia coli (MIC = 7.8 µM) bacteria. Cytoplasmic permeability assay results revealed that 25g acts primarily by depolarization of lipids in cytoplasmic membranes. The active compounds were also investigated for their cytotoxicity to human cells, lysis of lipid bilayers using tethered bilayer lipid membranes (tBLMs) and their activity against established biofilms of S. aureus and E. coli.

Amphipathic guanidine-embedded glyoxamide-based peptidomimetics as novel antibacterial agents and biofilm disruptors.

Antimicrobial resistance in bacteria is becoming increasingly prevalent, posing a critical challenge to global health. Bacterial biofilm formation is a common resistance mechanism that reduces the effectiveness of antibiotics. Thus, the development of compounds that can disrupt bacterial biofilms is a potential strategy to combat antimicrobial resistance. We report herein the synthesis of amphipathic guanidine-embedded glyoxamide-based peptidomimetics via ring-opening reactions of N-naphthoylisatins with amines and amino acids. These compounds were investigated for their antibacterial activity by the determination of minimum inhibitory concentration (MIC) against S. aureus and E. coli. Compounds 35, 36, and 66 exhibited MIC values of 6, 8 and 10 µg mL-1 against S. aureus, respectively, while compounds 55 and 56 showed MIC values of 17 and 19 µg mL-1 against E. coli, respectively. Biofilm disruption and inhibition activities were also evaluated against various Gram-positive and Gram-negative bacteria. The most active compound 65 exhibited the greatest disruption of established biofilms by 65% in S. aureus, 61% in P. aeruginosa, and 60% in S. marcescens respectively, at 250 µM concentration, while compound 52 inhibited the formation of biofilms by 72% in S. marcescens at 250 µM. We also report here the in vitro toxicity against MRC-5 human lung fibroblast cells. Finally, the pore forming capability of the three most potent compounds were tested using tethered bilayer lipid membrane (tBLM) technology.

Evidence of the Key Role of H3O+ in Phospholipid Membrane Morphology.

This study explains the importance of the phosphate moiety and H3O+ in controlling the ionic flux through phospholipid membranes. We show that despite an increase in the H3O+ concentration when the pH is decreased, the level of ionic conduction through phospholipid bilayers is reduced. By modifying the lipid structure, we show the dominant determinant of membrane conduction is the hydrogen bonding between the phosphate oxygens on adjacent phospholipids. The modulation of conduction with pH is proposed to arise from the varying H3O+ concentrations altering the molecular area per lipid and modifying the geometry of conductive defects already present in the membrane. Given the geometrical constraints that control the lipid phase structure of membranes, these area changes predict that organisms evolving in environments with different pHs will select for different phospholipid chain lengths, as is found for organisms near highly acidic volcanic vents (short chains) or in highly alkaline salt lakes (long chains). The stabilizing effect of the hydration shells around phosphate groups also accounts for the prevalence of phospholipids across biology. Measurement of ion permeation through lipid bilayers was made tractable using sparsely tethered bilayer lipid membranes with swept frequency electrical impedance spectroscopy and ramped dc amperometry. Additional evidence of the effect of a change in pH on lipid packing density is obtained from neutron reflectometry data of tethered membranes containing perdeuterated lipids.

It can W8: A community intervention to decrease distracted driving.

Researchers tested an intervention to decrease cell-phone use while driving on a university campus. A total of 3,827 driving observations were recorded on a campus roadway over a three-week period. The campus intervention, consisting of fear appeals, pledges, and behavioral prompts, was tested using an ABA reversal design (Baseline-Intervention-Baseline) with observed cell-phone use as the dependent measure. A Chi-Square test of independence indicated the percentage of drivers talking on a cell phone decreased significantly from 8.5% of 945 drivers at Baseline to 5.5% of 1,428 drivers following the Intervention. In contrast, the percentage of drivers observed texting increased significantly from 4% of 945 drivers at Baseline to 6.2% of 1,428 drivers following the Intervention. Additionally, safety-belt use was associated with the type of phone use observed. Findings were significantly different for women versus men. Results are discussed in the context of behavioral community intervention and gender differences in traffic-safety behavior.

Synthesis and biological evaluation of N-naphthoyl-phenylglyoxamide-based small molecular antimicrobial peptide mimics as novel antimicrobial agents and biofilm inhibitors.

Antimicrobial peptides (AMPs) are a key component of the human immune system. Synthetic AMP mimics represent a novel strategy to counteract the increasing incidence of antimicrobial resistance. Here, we describe the synthesis of novel glyoxamide derivatives via ring-opening reactions of N-hexanoyl, N-benzoyl and N-naphthoylisatins with N,N-dimethylethane-1,2-diamine and N,N-dimethylpropane-1,3-diamine. These were converted to both the hydrochloric acid (HCl) or quaternary ammonium iodide (MeI) salts and their antibacterial activity against Staphylococcus aureus was investigated by their zone-of-inhibition and minimum inhibitory concentration (MIC). The HCl salt 22b exhibited the lowest MIC of 16 µg mL(-1), whereas the corresponding MeI salt 22c had a MIC of 39 µg mL(-1). We also investigated the in vitro toxicity of active compounds against the MRC-5 normal human lung fibroblasts and their activity against established biofilm in S. aureus.

Influence of different etching modes on bond strength and fatigue strength to dentin using universal adhesive systems.

OBJECTIVES: The purpose of this study was to determine the dentin bonding ability of three new universal adhesive systems under different etching modes using fatigue testing. METHOD: Prime & Bond elect [PE] (DENTSPLY Caulk), Scotchbond Universal [SU] (3M ESPE), and All Bond Universal [AU] (Bisco) were used in this study. A conventional single-step self-etch adhesive, Clearfil Bond SE ONE [CS] (Kuraray Noritake Dental) was also included as a control. Shear bond strengths (SBS) and shear fatigue strength (SFS) to human dentin were obtained in the total-etch mode and self-etch modes. For each test condition, 15 specimens were prepared for the SBS and 30 specimens for SFS. SEM was used to examine representative de-bonded specimens, treated dentin surfaces and the resin/dentin interface for each test condition. RESULTS: Among the universal adhesives, PE in total-etch mode showed significantly higher SBS and SFS values than in self-etch mode. SU and AU did not show any significant difference in SBS and SFS between the total-etch mode and self-etch mode. However, the single-step self-etch adhesive CS showed significantly lower SBS and SFS values in the etch-and-rinse mode when compared to the self-etch mode. Examining the ratio of SFS/SBS, for PE and AU, the etch-and-rinse mode groups showed higher ratios than the self-etch mode groups. SIGNIFICANCE: The influence of different etching modes on dentin bond quality of universal adhesives was dependent on the adhesive material. However, for the universal adhesives, using the total-etch mode did not have a negative impact on dentin bond quality.

Mass gathering medicine: event factors predicting patient presentation rates.

This study was conducted to identify the event characteristics of mass gatherings that predict patient presentation rates held in a southeastern US university community. We conducted a retrospective review of all event-based emergency medical services (EMS) records from mass gathering patient presentations over an approximate 23 month period, from October 24, 2009 to August 27, 2011. All patrons seen by EMS were included. Event characteristics included: crowd size, venue percentage filled seating, venue location (inside/outside), venue boundaries (bounded/unbounded), presence of free water (i.e., without cost), presence of alcohol, average heat index, presence of climate control (i.e., air conditioning), and event category (football, concerts, public exhibitions, non-football athletic events). We identified 79 mass gathering events, for a total of 670 patient presentations. The cumulative patron attendance was 917,307 persons. The patient presentation rate (PPR) for each event was calculated as the number of patient presentations per 10,000 patrons in attendance. Overdispersed Poisson regression was used to relate this rate to the event characteristics while controlling for crowd size. In univariate analyses, increased rates of patient presentations were strongly associated with outside venues [rate ratio (RR) = 3.002, p < 0.001], unbounded venues (RR = 2.839, p = 0.001), absence of free water (RR = 1.708, p = 0.036), absence of climate control (RR = 3.028, p < 0.001), and a higher heat index (RR = 1.211 per 10-unit heat index increase, p = 0.003). The presence of alcohol was not significantly associated with the PPR. Football events had the highest PPR, followed sequentially by public exhibitions, concerts, and non-football athletic events. In multivariate models, the strong predictors from the univariate analyses retained their predictive significance for the PPR, together with heat index and percent seating. In the setting of mass event medical care, we note that several factors are strongly associated with an increased patient census, including outside (external) or unbounded venues, the absence of fee water (i.e., without cost), no climate control, percent (occupied) seating, and increasing heat index. Although the presence of alcohol is noted to increase patient needs, it does not do so significantly. Regarding event type, collegiate football games have the highest patient census among the range of other events studied. These findings should be considered during the process of EMS resource planning for mass gatherings.

Effect of a functional monomer (MDP) on the enamel bond durability of single-step self-etch adhesives.

The present study aimed to determine the effect of the functional monomer, 10-methacryloxydecyl dihydrogen phosphate (MDP), on the enamel bond durability of single-step self-etch adhesives through integrating fatigue testing and long-term water storage. An MDP-containing self-etch adhesive, Clearfil Bond SE ONE (SE), and an experimental adhesive, MDP-free (MF), which comprised the same ingredients as SE apart from MDP, were used. Shear bond strength (SBS) and shear fatigue strength (SFS) were measured with or without phosphoric acid pre-etching. The specimens were stored in distilled water for 24 h, 6 months, or 1 yr. Although similar SBS and SFS values were obtained for SE with pre-etching and for MF after 24 h of storage in distilled water, SE with pre-etching showed higher SBS and SFS values than MF after storage in water for 6 months or 1 yr. Regardless of the pre-etching procedure, SE showed higher SBS and SFS values after 6 months of storage in distilled water than after 24 h or 1 yr. To conclude, MDP might play an important role in enhancing not only bond strength but also bond durability with respect to repeated subcritical loading after long-term water storage.

Examining university students' sneezing and coughing etiquette.

University students' cough etiquette (CE) was observed and compared with the standards of the Centers for Disease Control and Prevention (CDC). Contrary to the CDC's recommendations, most students covered their mouth with their hands (53.3%) or did not cover at all (23.5%). Less than one-quarter of students used a sleeve arm, elbow, or tissue as advised by the CDC. Sex analysis revealed women were more likely to use a hand cover than men, whereas men were twice as likely to sneeze or cough into the air. Future research to study and improve student CE is encouraged.

Mass-gathering medicine: a descriptive analysis of a range of mass-gathering event types.

OBJECTIVE: To identify and evaluate the volume, nature, and severity of patient presentations encountered by emergency medical services (EMS) at all mass-gathering events held at or near a southeastern US university. In addition, to compare the existing literature base (single mass-gathering event held in large urban population centers) with a broader variety of events varying in crowd size and locations. METHODS: This was a retrospective review of all EMS records from mass-gathering patient presentations (individual-patient cases) between October 24, 2009, and August 27, 2011. All patrons seen by event-based EMS were included. Events categories included the following: football, concerts, public exhibitions, and nonfootball athletic events. Event volumes were defined as follows: low (<1000 patrons), medium (between 1001 and 15 000 patrons), and large (>15 000 patrons). Case presentation-management categories included the following: trauma, medical, and support (minimal medical intervention required, eg, minor dressing for abrasion, water, etc). Severity categories included the following: mild, moderate, and severe based on the following definitions using both provider assessment and the use of transport to a hospital: minor cases were considered non-life threats and did not result in a transport to a hospital; moderate cases were associated with transports to a hospital; and severe cases were life threats with transport to a hospital. RESULTS: We studied 79 events over the study period. Event volumes were 16.45% high, 79.75% medium, and 3.80% low. A total of 670 cases presented, with a mean of 8.48 cases/event. The football category had the highest mean number of cases with 37.09 cases/event, for a total of 408 cases. The nonfootball, athletic event category had the lowest mean number of cases at 1.83 cases/event. Most (81.82%) of the football events were classified as large volume. Support cases were the most common presentation (43.13%), followed closely by medical complaints (41.94%). Most cases were mild in severity (95.97%). There were 27 cases requiring transport to hospital, with 3 cases being life-threatening. The average patient age was 33 years, with 60.3% female sex. These features are similar to the published information on large event medical attendance. CONCLUSIONS: In this retrospective, descriptive study of a broad range of event type, the most common patient presentations at mass-gathering events were mild in severity, requiring minimal medical intervention. Both transports from the event to a hospital and the occurrence of life threats were uncommon. Our findings are similar to the data found in the existing medical literature.