Mechanism of sporicidal activity for the synergistic combination of peracetic acid and hydrogen peroxide

There is still great interest in controlling bacterial endospores. The use of chemical disinfectants and, notably, oxidizing agents to sterilize medical devices is increasing. With this in mind, hydrogen peroxide (H2O2) and peracetic acid (PAA) have been used in combination, but until now there has been no explanation for the observed increase in sporicidal activity. This study provides information on the mechanism of synergistic interaction of PAA and H2O2 against bacterial spores. We performed investigations of the efficacies of different combinations, including pretreatments with the two oxidizers, against wild-type spores and a range of spore mutants deficient in the spore coat or small acid-soluble spore proteins. The concentrations of the two biocides were also measured in the reaction vessels, enabling the assessment of any shift from H2O2 to PAA formation. This study confirmed the synergistic activity of the combination of H2O2 and PAA. However, we observed that the sporicidal activity of the combination is largely due to PAA and not H2O2. Furthermore, we observed that the synergistic combination was based on H2O2 compromising the spore coat, which was the main spore resistance factor, likely allowing better penetration of PAA and resulting in the increased sporicidal activity

Responsibility loadings for dental services by general dentists

Extent: 6p.BACKGROUND: Responsibility loadings determine relative value units of dental services that translate services into a common scale of work effort. The aims of this paper were to elicit responsibility loadings for a subset of dental services and to relate responsibility loadings to ratings of importance of the components of responsibility. METHODS: Responsibility loadings and ratings of components of responsibility were collected using mailed questionnaires from a random sample of Australian private general practice dentists in 2007 (response rate = 77%). RESULTS: Median responsibility loadings were 1.25 for an initial oral examination and for a 3+-surface amalgam restoration, 1.50 for a simple extraction and for root canal obturation (single canal), and 1.75 for subgingival curettage (per quadrant). Across the five services coefficients from a multivariate logit model showed that ratings of importance of knowledge (0.34), dexterity (0.24), physical effort (0.28) and mental effort (0.48) were associated with responsibility loadings (P < 0.05). CONCLUSIONS: The elicited median responsibility loadings showed agreement with previous estimates indicating convergent validity. Components of responsibility were associated with loadings indicating that components can explain and predict responsibility aspects of dental service provision.David S. Brennan and A. John Spence

Correcting the Bias of Empirical Frequency Parameter Estimators in Codon Models

Markov models of codon substitution are powerful inferential tools for studying biological processes such as natural selection and preferences in amino acid substitution. The equilibrium character distributions of these models are almost always estimated using nucleotide frequencies observed in a sequence alignment, primarily as a matter of historical convention. In this note, we demonstrate that a popular class of such estimators are biased, and that this bias has an adverse effect on goodness of fit and estimates of substitution rates. We propose a “corrected” empirical estimator that begins with observed nucleotide counts, but accounts for the nucleotide composition of stop codons. We show via simulation that the corrected estimates outperform the de facto standard estimates not just by providing better estimates of the frequencies themselves, but also by leading to improved estimation of other parameters in the evolutionary models. On a curated collection of sequence alignments, our estimators show a significant improvement in goodness of fit compared to the approach. Maximum likelihood estimation of the frequency parameters appears to be warranted in many cases, albeit at a greater computational cost. Our results demonstrate that there is little justification, either statistical or computational, for continued use of the -style estimators

Neonatal overfeeding by small-litter rearing sensitises hippocampal microglial responses to immune challenge:Reversal with neonatal repeated injections of saline or minocycline

The early-life period is extremely vulnerable to programming effects from the environment, many of which persist into adulthood. We have previously demonstrated that adult rats overfed as neonates have hypothalamic microglia that are hyper-responsive to an immune challenge, as well as hippocampal microglia that respond less efficiently to learning. We therefore hypothesised that neonatal overfeeding would alter the ability of hippocampal microglia to respond to an immune challenge with lipopolysaccharide (LPS) and that concomitant minocycline, a tetracycline antibiotic that suppresses microglial activity, could restore these responses. We induced neonatal overfeeding by manipulating the litter sizes in which Wistar rat pups were raised, so the pups were suckled in litters of four (neonatally overfed) or 12 (control-fed). We then examined the hippocampal microglial profiles 24 hour after an immune challenge with LPS and found that the neonatally overfed rats had dramatically increased microglial numbers in the hippocampus after immune challenge compared to control-fed rats. Attempts to reverse these effects with minocycline revealed repeated that neonatal injections, whether with minocycline or with saline, markedly suppressed microglial number and density throughout the hippocampus and abolished the difference between the groups in their responses to LPS. These data suggest that neonatal overfeeding not only can have lasting effects on hippocampal immune responses, but also that neonatal exposure to a protocol of repeated injections, irrespective of treatment, has a pronounced long-term impact, highlighting the importance of considering these effects when interpreting experimental data

Why going green feels good

Re​cent re​search found that when asked ex​plic​itly, peo​ple as​so​ci​ate (fu​ture) sus​tain​able ac​tions with pos​i​‐ tive in​stead of neg​a​tive emo​tions. This em​pir​i​cal find​ing im​plies that pol​icy mak​ers could har​ness peo​ple's in​trin​sic mo​ti​va​tion to pro​mote sus​tain​able ac​tions. It is how​ever not clear where this as​so​ci​a​tion be​tween sus​tain​able ac​tions and pos​i​tive emo​tions stems from. Why would peo​ple re​port that go​ing green feels good, given that such ac​tions of​ten re​quire more ef​fort or in​con​ve​nience? We ar​gue and show that the pre​‐ vi​ously found re​la​tion​ship be​tween sus​tain​able ac​tions and an​tic​i​pated pos​i​tive emo​tions is not merely a mat​ter of so​cial de​sir​abil​ity, but rather a mat​ter of mean​ing: act​ing sus​tain​ably is of​ten per​ceived as a moral choice and thus as a mean​ing​ful course of ac​tion, which can elicit pos​i​tive emo​tions. Specif​i​cally, we found that par​tic​i​pants also as​so​ci​ate sus​tain​able ac​tions with pos​i​tive in​stead of neg​a​tive emo​tions when us​ing an im​plicit as​so​ci​a​tion mea​sure – one that re​duces the like​li​hood of so​cially de​sir​able re​sponses (Study 1). More​over, par​tic​i​pants an​tic​i​pated more in​tense emo​tions when those ac​tions were mean​ing​ful to them: they felt more pos​i​tive about sus​tain​able ac​tions, and more neg​a​tive about un​sus​tain​able ac​tions, when they chose to en​gage in those ac​tions and when those ac​tions are con​sid​ered per​son​ally rel​e​vant to the in​di​vid​ual (Study 2). To​gether, these stud​ies ex​plain why act​ing green feels good, and sup​port the no​‐ tion that sus​tain​able ac​tions are in​deed ex​pected (not merely re​ported) to be in​trin​si​cally mo​ti​vat​ing

Eine verbesserte fluorimetrische Cortisolbestimmung im Serum

Die fluorimetrische Methode zur Bestimmung von Serumcortisol wurde durch blasenfreie Füllung einer Spezialküvette mittels Pumpvorrichtung, durch Benützung eines Spectralfluorimeters, sowie Verlegung des Meßzeitpunktes (80 min) und durch optimale Anregung (464 nm) und Emissionsmessung (522 nm) verbessert. Empfindlichkeit (<1 µg Cortisol/100 ml), Richtigkeit, Genauigkeit, Reproduzierbarkeit von Tag zu Tag (VK=6–7%) und Störfaktoren der Methode werden angegeben. Mit dieser Methode wurden Normalberciche für die 9 Uhr-Nüchterncortisolwerte und die i.v. ACTH-Belastung ermittelt. Bei NNR-insuffizienten Patienten (M. Addison; Zustand nach Operation eines Hypophysentumors; total Adrenalektomierte) wurden i.v. ACTH-Belastungen durchgeführt, wobei sich bereits beim 9 Uhr-Nüchterncortisolwert eine diagnostisch gut brauchbare Trennung gegenüber dem Normalbereich ergab. Unter Dexamethasonsubstitution wurden bei NNR-Insuffizienz sehr niedrige Cortisolspiegel gemessen, was für die Spezifität der Methode spricht. Dic Bestimmung des 24 Std-Rhythmus der Cortisolwerte bei NNR-Insuffizienten zeigte, daß besonders in den frühen Morgenstunden im Vergleich zu Normalpersonen erniedrigte Cortisolspiegel bestehen. Daraus wird ein besserer Verteilungsvorschlag für die Cortisol-substitution abgeleitet.The fluorimetric determination of serum cortisol was improved 1. using a pumpdevice to fill a special microcuvette avoiding the development of small bubbles, 2. using a recording spectrofluorometer with optimal absorption (464 nm) and emission (522 nm), and 3. allowing for maximal fluorescence of cortisol (80 min). Sensitivity (<1 µg cortisol/100 ml), accuracy, precision and specificity of the method are reported. Normal values of 9.00 a.m. serum cortisol (9.7–32.0 µg/100 ml) and of values before and after ACTH infusion tests were determined. For adrenal insufficiency (Addisons disease, total adrenalectomy, or after hypophysectomy) the 9.00 a.m. values of serum cortisol were generally satisfactory for diagnosis. In partial adrenal insufficiency ACTH infusion tests had to be performed. Very low levels of serum cortisol (2–4 µg/100 ml) were obtained, when patients with adrenal insufficiency were substituted with dexamethasone for three days, proving the specificity of the method. Determination of circadian rhythms of serum cortisol in patients with adrenal insufficiency on cortisol substitutive therapy in divided doses demonstrated cortisol levels far below the normal values during the carly morning hours. This situation should be improved by dividing the cortisol dose as follows: 6 a.m.: 10 mg, 10 a.m.: 5 mg, 2 p.m.: 5 mg and 8 p.m. or later: 10 mg cortisol

Passive Transdermal Systems Whitepaper Incorporating Current Chemistry, Manufacturing and Controls (CMC) Development Principles

In this whitepaper, the Manufacturing Technical Committee (MTC) of the Product Quality Research Institute has updated the 1997 Transdermal Drug Delivery Systems Scale-Up and Post Approval Change workshop report findings to add important new product development and control principles. Important topics reviewed include ICH harmonization, quality by design, process analytical technologies, product and process validation, improvements to control of critical excipients, and discussion of Food and Drug Administration’s Guidance on Residual Drug in Transdermal and Related Drug Delivery Systems as well as current thinking and trends on in vitro–in vivo correlation considerations for transdermal systems