Expanding the Spectrum of Antibiotics Capable of Killing Multidrug-Resistant Staphylococcus aureus and Pseudomonas aeruginosa

Infections from antibiotic-resistant Staphylococcus aureus and Pseudomonas aeruginosa are a serious threat because reduced antibiotic efficacy complicates treatment decisions and prolongs the disease state in many patients. To expand the arsenal of treatments against antimicrobial-resistant (AMR) pathogens, 600-Da branched polyethylenimine (BPEI) can overcome antibiotic resistance mechanisms and potentiate β-lactam antibiotics against Gram-positive bacteria. BPEI binds cell-wall teichoic acids and disables resistance factors from penicillin binding proteins PBP2a and PBP4. This study describes a new mechanism of action for BPEI potentiation of antibiotics generally regarded as agents effective against Gram-positive pathogens but not Gram-negative bacteria. 600-Da BPEI is able to reduce the barriers to drug influx and facilitate the uptake of a non-β-lactam co-drug, erythromycin, which targets the intracellular machinery. Also, BPEI can suppress production of the cytokine interleukin IL-8 by human epithelial keratinocytes. This enables BPEI to function as a broad-spectrum antibiotic potentiator, and expands the opportunities to improve drug design, antibiotic development, and therapeutic approaches against pathogenic bacteria, especially for wound care.     

Health economics and cost implications of anxiety and other mental disorders in the United States

BACKGROUND: Mental disorders impose a multi-billion dollar burden on the economy each year; translating the burden into economic terms is important to facilitate formulating policies about the use of resources. METHODS: For direct costs, data were obtained from national household interview and provider surveys; for morbidity costs, a timing model was used that measures the lifetime effect on current income of individuals with mental disorders, taking into account the timing of onset and the duration of these disorders, based on regression analysis of Epidemiologic Catchment Area study data. RESULTS: The total economic costs of mental disorders amounted to US$147.8 billion in 1990. Anxiety disorders are the most costly, amounting to $46.6 billion, or 31.5% of the total; schizophrenic disorders accounted for $32.5 billion, affective disorders for $30.4 billion, and other mental disorders for $38.4 billion. CONCLUSIONS: Mental illnesses, especially anxiety disorders, are costly to society. Although anxiety disorders have a higher prevalence than affective disorders and schizophrenia, use of medical care services is lowest for anxiety disorders. Anxiety disorders appear to be under-recognised and untreated even though treatment interventions have been shown to be effective and can be delivered in a cost-efficient manner.     

Protein thermostability above 100 degreesC: a key role for ionic interactions

The discovery of hyperthermophilic microorganisms and the analysis of hyperthermostable enzymes has established the fact that multisubunit enzymes can survive for prolonged periods at temperatures above 100 degreesC. We have carried out homology-based modeling and direct structure comparison on the hexameric glutamate dehydrogenases from the hyperthermophiles Pyrococcus furiosus and Thermococcus litoralis whose optimal growth temperatures are 100 degreesC and 88 degreesC, respectively, to determine key stabilizing features. These enzymes, which are 87% homologous, differ 16-fold in thermal stability at 104 degreesC. We observed that an intersubunit ion-pair network was substantially reduced in the less stable enzyme from T. litoralis, and two residues were then altered to restore these interactions. The single mutations both had adverse effects on the thermostability of the protein. However, with both mutations in place, we observed a fourfold improvement of stability at 104 degreesC over the wild-type enzyme. The catalytic properties of the enzymes were unaffected by the mutations. These results suggest that extensive ion-pair networks may provide a general strategy for manipulating enzyme thermostability of multisubunit enzymes. However, this study emphasizes the importance of the exact local environment of a residue in determining its effects on stability.     

Localization of dopamine1A receptor mRNA in different vascular beds in rat: a nonradioactive in situ hybridization study

In situ hybridization of a biotin-labeled specific dopamine1A (D1A) receptor gene oligonucleotide probe combined with computer-assisted image analyzer was used to directly visualize D1A receptor mRNA and quantify the relative mRNA levels in sections of rat aorta and pulmonary and caudal arteries. Positive D1A receptor mRNA signals were found in rat aorta and pulmonary arteries, while no specific signals could be detected in the caudal artery. D1A receptor mRNA was located mainly within the medial layer of aorta, with intimal distribution in the pulmonary artery. The density of D1A receptor mRNA in different vascular beds demonstrated heterogeneity. D1A receptor mRNA levels in the aorta were much higher than those in the pulmonary artery (p < 0.01). These results demonstrate the existence of D1A receptor mRNA in both aorta and pulmonary beds, although with different distribution and density. The results further support the heterogeneity of the D1A receptor in different vascular beds.     

The effects of catalyst surface heterogeneity on the fischer-tropsch synthesis

We find that the surface energetic heterogeneity of Fischer-Tropsch catalysts is either not important kinetically or may be masked by the effect of increasing molecular size, so that the classical Anderson-Schulz-Flory distribution is routinely observed in product distributions. The anomalous yields of C₁ and C₂ observed in many cases may also be due to surface heterogeneity but can in practice be readily, and more conveniently, accounted for by assigning individual rate constants to their formation. The “break” sometimes observed in ASF distributions cannot be explained by surface heterogeneity and is best explained by the presence of two distinct modes of product formation.     

No effect of creatine supplementation on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats

Background

Exacerbated oxidative stress is thought to be a mediator of arterial hypertension. It has been postulated that creatine (Cr) could act as an antioxidant agent preventing increased oxidative stress. The aim of this study was to investigate the effects of nine weeks of Cr or placebo supplementation on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats (SHR).

Findings

Lipid hydroperoxidation, one important oxidative stress marker, remained unchanged in the coronary artery (Cr: 12.6 ± 1.5 vs. Pl: 12.2 ± 1.7 nmol·mg^-1; p = 0.87), heart (Cr: 11.5 ± 1.8 vs. Pl: 14.6 ± 1.1 nmol·mg^-1; p = 0.15), plasma (Cr: 67.7 ± 9.1 vs. Pl: 56.0 ± 3.2 nmol·mg^-1; p = 0.19), plantaris (Cr: 10.0 ± 0.8 vs. Pl: 9.0 ± 0.8 nmol·mg^-1; p = 0.40), and EDL muscle (Cr: 14.9 ± 1.4 vs. Pl: 17.2 ± 1.5 nmol·mg^-1; p = 0.30). Additionally, Cr supplementation affected neither arterial blood pressure nor heart structure in SHR (p > 0.05).

Conclusions

Using a well-known experimental model of systemic arterial hypertension, this study did not confirm the possible therapeutic effects of Cr supplementation on oxidative stress and cardiovascular dysfunction associated with arterial hypertension.     

Composition of Chemical Attractants Affects Trap Catches of the Australian Sheep Blowfly, Lucilia cuprina, and Other Blowflies

Numbers of Lucilia cuprina (Australian sheep blowfly), Chrysomya spp., and Calliphora spp. blowflies caught on sticky traps baited with various synthetic attractants or a standard liver/sodium sulfide attractant in western Queensland were recorded. Numbers of each genus collected were influenced by the composition of the chemical attractants. Attractant mixtures based on 2-mercaptoethanol, indole, butanoic/pentanoic acid, and a sodium sulfide solution gave 5- to 20-fold higher L. cuprina catches than the liver standard. These blends attracted similar numbers of Chrysomya spp. (0.85-2.7x) and fewer Calliphora spp. (0.02-0.2x) compared to the liver standard. These synthetic attractants were more effective and selective for L. cuprina than the standard liver/sodium sulfide attractant, and they can be packaged in controlled-release dispensers to generate constant, prolonged release of the attractant.     

Color harmonies in packaging

The goal of this research was to determine whether or not there was a difference between consumer preferences for color harmonies for products where external labels and visible product existed simultaneously. Using established color theory, transparent packages containing visible products with colored labels were evaluated. Eye tracking metrics and overall preference testing were used to assess these products. Eye tracking data yielded quantitative data that was statistically analyzed using analysis of variance. A post experiment survey was given to participants to collect demographics and additional data was completed through chi‐squared tests for association. No significant difference was found between color harmonies and preference, nor was there significance for the eye tracking metrics. These results of no significance are ideal for designers because it gives them the freedom to use their judgment when designing packaging labels. © 2016 Wiley Periodicals, Inc. Col Res Appl, 42, 50–59, 2017     

GRAPHICAL TECHNIQUE FOR MODELING INTEGRATING (Non–SELF-REGULATING) PROCESSES WITHOUT STEADY-STATE PROCESS DATA

Model-fitting techniques for controller tuning that require the process to be initially at steady state cannot generally be used with integrating (non–self-regulating) processes. To address this issue, a graphical model-fitting technique is detailed and demonstrated for determination of first order plus dead time integrating model parameters from integrating process response plots. The resulting model parameters can be used directly in a range of tuning correlations designed specifically for integrating processes. The advantage of this technique is that it requires only two periods of constant manipulated and disturbance variables sustained just long enough for the process variable to respond and establish a clear slope. This is an important benefit because integrating processes generally cannot be maintained at an initial steady state as required when using techniques published for self-regulating processes. The result is an industry-friendly method. The method is demonstrated for level control in a pumped tank, a classical challenge in industrial practice. Both a simulation and a bench-scale experimental system are used in the demonstration studies.