bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers and facilitators to undertaking nutritional screening of patients: a systematic review
Authors: Green S. M. , James E. P.
Published: January 2013

Background

Recent reports have suggested that registered nurses may not screen patients admitted to their care for malnutrition. The objective of this integrative review was to locate and review published research investigating barriers and facilitators to nutritional screening by nurses.

Methods

A systematic search for relevant English language publications was conducted through CINAHL®, Web of Science, MEDLINE® and EMBASE and an Internet search engine (completed November 2011). Reference lists of relevant publications were also searched. Search terms included nursing, dietetics, nutrition disorders and screening, as well as associated MeSH® terms and Subject Headings. Six hundred and sixteen publications were identified and 605 were excluded. Publications reporting research concerning barriers and facilitators to nutritional screening by nurses were selected using exclusion and inclusion criteria. These were reviewed and the key findings described, categorised, combined, reviewed and refined to create themes.

Results

Eleven publications were reviewed. Publications primarily reported hospital‐based studies undertaken in three continents and considered barriers rather than facilitators. Five themes emerged: organisational culture, competing priorities, the value of clinical judgement, training and education, and discrepancy between attitudes and practice.

Conclusions

Studies primarily involved acute care and indicated that routine screening for malnutrition will not take place unless it is considered an integral part of nursing assessment that is required by policy and resourced appropriately. Qualitative studies investigating barriers and facilitators to screening for malnutrition in community settings are needed and research is required to test interventions designed to modify or remove barriers and facilitate screening.
Systematic review of randomised controlled trials of the effects of caffeine or caffeinated drinks on blood glucose concentrations and insulin sensitivity in people with diabetes mellitus
Authors: Whitehead N. , White H.
Published: January 2013

Background

Compounds other than macronutrients have been shown to influence blood glucose concentrations and insulin sensitivity in people with diabetes, with caffeine being one such substance. The present study systematically reviewed the evidence of the effects of caffeine on blood glucose concentrations and/or insulin sensitivity in people with diabetes.

Methods

Four databases, including MEDLINE and EMBASE, were searched up to 1 February 2012. Randomised controlled trials (RCTs) investigating the effects of caffeine on blood glucose and/or insulin sensitivity in humans, diagnosed with type I, type II or gestational diabetes mellitus (GDM), were included. Quality assessment and data extraction were conducted and agreed by both authors.

Results

Of 253 articles retrieved, nine trials (134 participants) were identified. Trials in people with type II diabetes demonstrated that the ingestion of caffeine (approximately 200–500 mg) significantly increased blood glucose concentrations by 16–28% of the area under the curve (AUC) and insulin concentrations by 19–48% of the AUC when taken prior to a glucose load, at the same time as decreasing insulin sensitivity by 14–37%. In type I diabetes, trials indicated enhanced recognition and a reduced duration of hypoglycaemic episodes following ingestion of 400–500 mg caffeine, without altering glycated haemoglobin. In GDM, a single trial demonstrated that approximately 200 mg of caffeine induced a decrease in insulin sensitivity by 18% and a subsequent increase in blood glucose concentrations by 19% of the AUC.

Conclusions

Evidence indicates a negative effect of caffeine intake on blood glucose control in individuals with type II diabetes, as replicated in a single trial in GDM. Larger‐scale RCTs of longer duration are needed to determine the effects of timing and dose. Early indications of a reduced duration and an improved awareness of hypoglycaemia in type I diabetes require further confirmation.
The transcription factor Pitx3 is expressed selectively in midbrain dopaminergic neurons susceptible to neurodegenerative stress
Authors: Luk Kelvin C. , Rymar Vladimir V. , van den Munckhof Pepijn , Nicolau Stefan , Steriade Claude , Bifsha Panojot , Drouin Jacques , Sadikot Abbas F.
Published: January 2013

The homeodomain transcription factor Pitx3 is critical for the survival of midbrain dopaminergic (mDA) neurons. Pitx3‐deficient mice exhibit severe but selective developmental loss of mDA neurons, with accompanying locomotor deficits resembling those seen in Parkinson's disease (PD) models. Here, we identify specific mDA cell subpopulations that are consistently spared in adult Pitx3‐hypomorphic (aphakia) mice, demonstrating that Pitx3 is not indiscriminately required by all mDA neurons for their survival. In aphakia mice, virtually all surviving mDA neurons in the substantia nigra (SN) and the majority of neurons in the adjacent ventral tegmental area (VTA) also express calbindin‐D28k, a calcium‐binding protein previously associated with resistance to injury in PD and in animal models. Cell‐mapping studies in wild‐type mice revealed that Pitx3 is primarily expressed in the ventral SN, a region particularly susceptible to MPTP and other dopaminergic neurotoxins. Furthermore, Pitx3‐expressing SN cells are preferentially lost following MPTP treatment. Finally, SN mDA neurons in Pitx3 hemizygous mice show increased sensitivity when exposed to MPTP. Thus, SN mDA neurons are represented by at least two distinct subpopulations including MPTP‐resistant Pitx3‐autonomous, calbindin‐positive neurons, and calbindin‐negative Pitx‐3‐dependent cells that display elevated vulnerability to toxic injury, and probably correspond to the subpopulation that degenerates in PD. Impairment of Pitx3‐dependent pathways therefore increases vulnerability of mDA neurons to toxic injury. Together, these data suggest a novel link between Pitx3 function and the selective pattern of mDA cell loss observed in PD.
nAChR‐induced octopamine release mediates the effect of nicotine on a startle response in Drosophila melanogaster
Authors: Fuenzalida‐Uribe Nicolás , Meza Rodrigo C. , Hoffmann Hernán A. , Varas Rodrigo , Campusano Jorge M.
Published: January 2013

Biogenic amines (BAs) play a central role in the generation of complex behaviors in vertebrates and invertebrates, including the fly Drosophila melanogaster. The comparative advantages of Drosophila as a genetic model to study the contribution of BAs to behaviors stumble upon the difficulty to access the fly brain to ask relevant physiological questions. For instance, it is not known whether the activation of nicotinic acetylcholine receptors (nAChRs) induces the release of BAs in fly brain, a phenomenon associated to several behaviors in vertebrates. Here, we describe a new preparation to study the efflux of BAs in the adult fly brain by in vitro chronoamperometry. Using this preparation we show that nAChR agonists including nicotine induce a fast, transient, dose‐dependent efflux of endogenous BAs, an effect mediated by α‐bungarotoxin‐sensitive nAChRs. By using different genetic tools we demonstrate that the BA whose efflux is induced by nAChR activation is octopamine (Oct). Furthermore, we show that the impairment of a mechanically induced startle response after nicotine exposure is not observed in flies deficient in Oct transmission. Thus, our data show that the efflux of BAs in Drosophila brain is increased by nAChR activation as in vertebrates, and that then AChR‐induced Oct release could have implications in a nicotine‐induced behavioral response.
Methodological quality and descriptive characteristics of prosthodontic‐related systematic reviews
Authors: Aziz T. , Compton S. , Nassar U. , Matthews D. , Ansari K. , Flores‐Mir C.
Published: January 2013

Ideally, healthcare systematic reviews (SRs) should be beneficial to practicing professionals in making evidence‐based clinical decisions. However, the conclusions drawn from SRs are directly related to the quality of the SR and of the included studies. The aim was to investigate the methodological quality and key descriptive characteristics of SRs published in prosthodontics. Methodological quality was analysed using the Assessment of Multiple Reviews (AMSTAR) tool. Several electronic resources (MEDLINE, EMBASE, Web of Science and American Dental Association's Evidence‐based Dentistry website) were searched. In total 106 SRs were located. Key descriptive characteristics and methodological quality features were gathered and assessed, and descriptive and inferential statistical testing performed. Most SRs in this sample originated from the European continent followed by North America. Two to five authors conducted most SRs; the majority was affiliated with academic institutions and had prior experience publishing SRs. The majority of SRs were published in specialty dentistry journals, with implant or implant‐related topics, the primary topics of interest for most. According to AMSTAR, most quality aspects were adequately fulfilled by less than half of the reviews. Publication bias and grey literature searches were the most poorly adhered components. Overall, the methodological quality of the prosthodontic‐related systematic was deemed limited. Future recommendations would include authors to have prior training in conducting SRs and for journals to include a universal checklist that should be adhered to address all key characteristics of an unbiased SR process.
Changes in activity and structure of jaw muscles in Parkinson's disease model rats
Authors: Nakamura S. , Kawai N. , Ohnuki Y. , Saeki Y. , Korfage J. A. M. , Langenbach G. E. J. , Kitayama T. , Watanabe M. , Sano R. , Tanne K. , Tanaka E.
Published: January 2013

Parkinson's disease (PD), a major neurological disease, is characterised by a marked loss of dopaminergic neurons in the substantia nigra. Patients with PD frequently show chewing and swallowing dysfunctions, but little is known about the characteristics of their stomatognathic functions. The purpose of this study was to evaluate the influence of PD on jaw muscle fibre and functions. PD model rats were made by means of the injection of 6‐hydroxydopamine (6‐OHDA) into the striatum of 8‐week‐old Sprague‐Dawley male rats. Five weeks after the injection, a radio‐telemetric device was implanted to record muscle activity continuously from the superficial masseter and anterior belly of digastric muscles. Muscle activity was recorded for 3 days and was evaluated by the total duration of muscle activity per day (duty time). After recording the muscle activities, jaw muscles were isolated for immunohistochemical and PCR analyses. In PD model rats, the following findings of the digastrics muscles verify that compared to the control group: (i) the higher duty time exceeding 5% of the peak activity level, (ii) the higher expression of the mRNA of myosin heavy chain type I, and (iii) the tendency for fast to slow fibre‐type transition. With respect to the masseter muscle, there were no significant differences in all analyses. In conclusion, PD leads to the changes in the jaw behaviours, resulting in a PD‐specific chewing and swallowing dysfunctions.
Expression of αvβ6 integrin and collagen fibre in oral squamous cell carcinoma: association with clinical outcomes and prognostic implications
Authors: Li Hai‐Xia , Zheng Jin‐Hua , Fan Hai‐Xia , Li Hui‐Ping , Gao Zhong‐Xiuzi , Chen Dong
Published: January 2013

Background

This study aims to investigate the expression and significance of the αvβ6 integrin, collagen fibres and matrix metalloproteinases (MMP)‐3 in oral squamous cell carcinoma (OSCC) and to analyse the possible regulatory relationships between αvβ6, collagen fibres and MMP‐3.

Materials and Methods

A series of 80 patients (mean age 56.4 years) diagnosed with OSCC were enrolled. Associations between αvβ6, MMP‐3, collagen fibre expression levels and clinicopathological parameters were evaluated using the Fisher exact test. Survival analysis was performed with Kaplan–Meier curves. Spearman rank correlation was used to analyse interactions between αvβ6, MMP‐3 and collagen fibres.

Results

αvβ6 and MMP‐3 were strongly expressed in human OSCC, especially at the peripheral borders of invasive tumour islands, and collagen fibres were generally disrupted and degraded in the same areas. The expression intensity of αvβ6 was associated with the differentiation state of cells. β6 mRNA was expressed in almost all cancer cells. In carcinomas, αvβ6 and MMP‐3 expression were correlated with the distribution of collagen fibres.

Conclusions

Tumour cells highly expressing αvβ6 have a strong capability for invasion and migration, due to concomitant protease production and the destruction and remodelling of collagen fibres. Increased αvβ6 integrin and MMP‐3 expression and collagen fibre changes in human OSCCs are related to unfavourable clinical prognostic factors and decreased survival.
Effect of mineral mixture and antioxidant supplementation on growth, reproductive performance and adaptive capability of Malpura ewes subjected to heat stress
Authors: Sejian V. , Singh A. K. , Sahoo A. , Naqvi S. M. K.
Published: January 2013

This study was conducted to evaluate the effect of mineral and antioxidant supplementation on growth, reproductive performance and physiological adaptability of heat‐stressed Malpura ewes. The study was conducted for a period of 21 days in 21 adult Malpura ewes. The ewes were randomly divided into three groups with seven animals each viz. GI (control; n = 7), GII (heat stress; n = 7) and GIII (heat stress + mineral and antioxidant supplementation; n = 7). The animals were stall fed ad libitum with the diet consisting of 70% roughage and 30% concentrate. GI ewes were maintained under normal controlled condition in the shed, while GII and GIII ewes were subjected to heat stress by exposing them to 42 °C in the climatic chamber. The parameters studied were feed intake (FI), water intake (WI), body weight, body condition score (BCS), physiological, biochemical and endocrine responses. Heat stress significantly altered FI, water intake, BCS, respiration rate and rectal temperature in the afternoon, oestrus duration, estradiol, progesterone, Hb, PCV, plasma glucose, total protein, cortisol, T3 and T4 levels while mineral and antioxidant supplementation ameliorated this heat stress effect on the parameters studied. Further, the adverse effect of heat stress on the productive and reproductive efficiency of Malpura ewes was reduced considerably by mineral mixture and antioxidant supplementation. This is evident from the non‐significant difference in BCS, oestrus duration and plasma estradiol between GI and GIII in this study. Hence, it is very pertinent to conclude from this study that mineral mixture and antioxidant supplementation were able to protect Malpura ewes against heat stress.
Ecological momentary assessment of daytime symptoms during sleep restriction therapy for insomnia
Authors: Miller Christopher B. , Kyle Simon D. , Marshall Nathaniel S. , Espie Colin A.
Published: January 2013

This study profiles changes in self‐reported daytime functioning during sleep restriction therapy (SRT) for insomnia. Ecological momentary assessment (EMA) captured point‐in‐time symptomatology to map the time–course of symptoms. We hypothesized a deterioration (week 1) followed by improvements at week 3 of therapy relative to baseline. Nine patients with psychophysiological insomnia completed the Daytime Insomnia Symptom Scale (DISS) at rise‐time, 12:00 hours, 18:00 hours and bedtime for 1 week before and 3 weeks during SRT. Four validated factors from the DISS were analyzed (alert cognition, positive mood, negative mood and sleepiness/fatigue) across 28 days yielding 17 170 data points. Factors evaluated week (baseline versus weeks 1 and 3) and time of day symptomatology. Insomnia Severity Index scores decreased significantly pre‐to‐post treatment (mean 18 versus 7). Reflecting acute effects of SRT, significant differences were found for all factors, except negative mood, between baseline and week 1 of SRT, suggesting adverse effects. By week 3, sleepiness/fatigue and negative mood decreased significantly compared to baseline, and positive mood showed a trend towards improvement (P = 0.06). Sleepiness/fatigue displayed a significant week × time of day interaction, explained by a reduction in sleepiness/fatigue at every daytime assessment point (except bedtime, which remained high). A significant interaction for alert cognition was associated with reduction in alertness at bedtime by week 3 and an increase in alertness at rise‐time, suggesting that SRT not only improves sleep, but moderates alertness and sleepiness in therapeutic ways. Initial SRT is associated with an increase in sleepiness/fatigue and a decrease in alert cognition.
Association between obstructive sleep apnea severity and endothelial dysfunction in an increased background of cardiovascular burden
Authors: Seif Fadi , Patel Sanjay R. , Walia Harneet , Rueschman Michael , Bhatt Deepak L. , Gottlieb Daniel J. , Lewis Eldrin F. , Patil Susheel P. , Punjabi Naresh M. , Babineau Denise C. , Redline Susan , Mehra Reena
Published: January 2013

The objective of this study is to examine whether increasing obstructive sleep apnea (OSA) severity is associated with worsening endothelial function. The design is a cross‐sectional examination of the baseline assessment of a multi‐centre randomized controlled clinical trial examining the effects of oxygen, continuous positive airway pressure (CPAP) therapy or lifestyle modifications on cardiovascular biomarkers. Participants were recruited from cardiology clinics at four sites. Participants with an apnea–hypopnea index (AHI) of 15–50 and known cardio/cerebrovascular disease (CVD) or CVD risk factors were included. OSA severity indices [oxygen desaturation index (ODI), AHI and percentage of sleep time below 90% oxygen saturation (total sleep time <90)] and a measure of endothelium‐mediated vasodilatation [Framingham reactive hyperaemia index (F‐RHI) derived from peripheral arterial tonometry (PAT)] were assessed. The sample included 267 individuals with a mean AHI of 25.0 ± 8.5 SD and mean F‐RHI 0.44 ± 0.38. In adjusted models, the slope of the relationship between ODI and F‐RHI differed above and below an ODI of 24.6 (P = 0.04), such that above an ODI of 24.6 there was a marginally significant decline in the geometric mean of the PAT ratio by 3% [95% confidence interval (CI): 0%, 5%; P = 0.05], while below this point, there was a marginally significant incline in the geometric mean of the PAT ratio by 13% (95% CI: 0%, 27%; P = 0.05) per 5‐unit increase in ODI. A similar pattern was observed between AHI and F‐RHI. No relation was noted with total sleep time <90 and F‐RHI. There was evidence of a graded decline in endothelial function in association with higher levels of intermittent hypoxaemia.
The effects of testosterone on ventilatory responses in men with obstructive sleep apnea: a randomised, placebo‐controlled trial
Authors: Killick Roo , Wang David , Hoyos Camilla M. , Yee Brendon J. , Grunstein Ronald R. , Liu Peter Y.
Published: January 2013

We recently showed that testosterone therapy worsens sleep‐disordered breathing at 6–7 weeks, but not after 18 weeks, in men with obstructive sleep apnea. Changes in ventilatory chemoreflexes may be responsible. The effect of testosterone on ventilatory chemoreflexes in men with obstructive sleep apnea has not been systematically studied before. Twenty‐one obese men with obstructive sleep apnea, a subgroup of our recent report, were randomised in an 18‐week, randomised, double‐blind, placebo‐controlled, parallel group trial to three intramuscular injections (0, 6, 12 weeks) of either 1000 mg testosterone undecanoate (n = 10) or placebo (n = 11). Awake ventilatory chemoreflex testing was performed before (week 0), during (week 6) and at the end of treatment (week 18) to determine the ventilatory carbon dioxide recruitment threshold and chemosensitivity. Sleep and breathing was assessed by overnight polysomnography at 0, 7 and 18 weeks. Serum hormones levels were measured at every visit. A significant increase in blood testosterone levels (5.65 nmol L−1, 0.51–10.8 nmol L−1, P = 0.03) and lean muscle mass (2.36 kg, 0.8–3.9 kg, P = 0.007) between the two groups was observed as expected. No significant differences were seen in ventilatory chemoreflexes between the two groups at 6 weeks or at 18 weeks. However, positive correlations were observed between changes in serum testosterone and hyperoxic ventilatory recruitment threshold (r = 0.55, P = 0.03), and between changes in hyperoxic ventilatory recruitment threshold and time spent with oxygen saturations during sleep <90% (r = 0.57, P = 0.03) at 6–7 weeks, but not at 18 weeks. Time‐dependent alterations in ventilatory recruitment threshold may therefore mediate the time‐dependent changes in sleep breathing observed with testosterone.
T‐Type Ca2+ Channels in Cerebral Arteries: Approaches, Hypotheses, and Speculation
Authors: Harraz Osama F. , Welsh Donald G.
Published: January 2013

Cerebral blood flow is controlled by a network of resistance arteries that dilate and constrict to mechanical and chemical stimuli. Vasoactive stimuli influence arterial diameter through alterations in resting membrane potential and the influx of Ca2+ through voltage‐gated Ca2+ channels. Historically, L‐type Ca2+ channels were thought to be solely expressed in cerebral arterial smooth muscle. Recent studies have, however, challenged this perspective, by providing evidence of T‐type Ca2+ channels in vascular tissues. This perspective piece will introduce T‐type Ca2+ channels, their electrophysiological properties, and potential roles in arterial tone development. We begin with a brief overview of Ca2+ channels and a discussion of the approaches used to isolate this elusive conductance. We will then speculate on how the two T‐type Ca2+ channels expressed in cerebral arterial smooth muscle might differentially influence arterial tone. This discovery of T‐type Ca2+ channels alters our traditional understanding of Ca2+ dynamics in vascular tissue and fosters new avenues of research and insight into the basis of arterial tone development.
Fermentative 2‐carbon metabolism produces carcinogenic levels of acetaldehyde in Candida albicans
Authors: Marttila E. , Bowyer P. , Sanglard D. , Uittamo J. , Kaihovaara P. , Salaspuro M. , Richardson M. , Rautemaa R.
Published: January 2013

Acetaldehyde is a carcinogenic product of alcohol fermentation and metabolism in microbes associated with cancers of the upper digestive tract. In yeast acetaldehyde is a by‐product of the pyruvate bypass that converts pyruvate into acetyl‐Coenzyme A (CoA) during fermentation. The aims of our study were: (i) to determine the levels of acetaldehyde produced by Candida albicans in the presence of glucose in low oxygen tension in vitro; (ii) to analyse the expression levels of genes involved in the pyruvate‐bypass and acetaldehyde production; and (iii) to analyse whether any correlations exist between acetaldehyde levels, alcohol dehydrogenase enzyme activity or expression of the genes involved in the pyruvate‐bypass. Candida albicans strains were isolated from patients with oral squamous cell carcinoma (n = 5), autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) patients with chronic oral candidosis (n = 5), and control patients (n = 5). The acetaldehyde and ethanol production by these isolates grown under low oxygen tension in the presence of glucose was determined, and the expression of alcohol dehydrogenase (ADH1 and ADH2), pyruvate decarboxylase (PDC11), aldehyde dehydrogenase (ALD6) and acetyl‐CoA synthetase (ACS1 and ACS2) and Adh enzyme activity were analysed. The C. albicans isolates produced high levels of acetaldehyde from glucose under low oxygen tension. The acetaldehyde levels did not correlate with the expression of ADH1, ADH2 or PDC11 but correlated with the expression of down‐stream genes ALD6 and ACS1. Significant differences in the gene expressions were measured between strains isolated from different patient groups. Under low oxygen tension ALD6 and ACS1, instead of ADH1 or ADH2, appear the most reliable indicators of candidal acetaldehyde production from glucose.
Clinical evidence on the efficacy and safety of an antioxidant optimized 1.5% salicylic acid (SA) cream in the treatment of facial acne: an open, baseline‐controlled clinical study
Authors: Zheng Yue , Wan Miaojian , Chen Haiyan , Ye Congxiu , Zhao Yue , Yi Jinling , Xia Yue , Lai Wei
Published: January 2013

Background/purpose

Acne pathogenesis is multifactorial and includes inflammation. Combining active ingredients targeting multiple components of acne pathogenesis may yield optimal outcomes. This study investigates the safety and efficacy of an antioxidant optimized topical salicylic acid (SA) 1.5% cream containing natural skin penetration enhancers in combination with antioxidant activity for treatment of facial acne.

Methods

A total of 20 patients with facial acne, aged 19–32 years (2 males, 18 females; mean age 26.1 ± 3.2), were enrolled. Patients were treated with topical 1.5% SA cream and instructed to apply the cream as a thin film over the affected area twice daily (in the morning and evening) for 4 weeks. Inflammatory severity, numbers of papules and pustules were evaluated by investigators at day 0 and weekly, and patients ranked their improvement.

Results

In all, 95% of patients improved: 20% had complete clearing, 30% had significantly improved, 15% had moderate improvement, 30% had mild improved, and there was no response in 5% of the patients by 4 weeks of treatment. No side effects were observed.

Conclusion

This study demonstrates the efficacy and safety of this optimized topical 1.5% SA cream containing natural skin penetration enhancers in combination with antioxidant activity when applied twice daily for the reduction of facial acne; in particular, it is most effective for mild‐to‐moderate acne.
Comparing the rates of absorption and weight loss during a desorption test using near infrared spectroscopy
Authors: Qassem M. , Kyriacou P. A.
Published: January 2013

The importance of determining skin hydration has over the years prompt the development of many instruments and methods, specifically designed to assess this parameter or water contents especially in the stratum corneum, and have greatly matured to suit different anatomical sites and measure multiple attributes. Of those, Near Infrared Spectroscopy (NIRS) has gained wide interest as a precise, safe, fast and noninvasive technique for determining skin hydration due to its high sensitivity to hydrogen bonding and ability to measure the amount of water in skin directly using the intensities of overtone and combination bands of OH and HOH water bonds occurring in the NIR region, that are good indicators of the state of skin hydration. This paper reports near infrared spectrophotometric measurements using a highly sophisticated spectrophotometer in the region of 1000‐2500 nm to study the water uptake and dehydration properties of skin in vitro using samples of porcine skin. Initial results of pure liquid water and skin samples have clearly displayed the prominent bands associated with water content, and desorption tests have been able to verify changes in these bands associated with water content, although a clear correlation between the rates of weight loss and absorbance loss at various hydration periods has not yet been established. These preliminary results are expected to further explain the relationship between water and skin, and its role within, in hope to aid the future development of a portable instrument based on near infrared spectroscopy that would be capable of directly measuring skin hydration and/or water content in a fast and noninvasive manner.
International guidelines for thein vivoassessment of skin properties in non‐clinical settings: Part 2. transepidermal water loss and skin hydration
Authors: Plessis Johan du , Stefaniak Aleksandr , Eloff Fritz , John Swen , Agner Tove , Chou Tzu‐Chieh , Nixon Rosemary , Steiner Markus , Franken Anja , Kudla Irena , Holness Linn
Published: January 2013

Background

There is an emerging perspective that it is not sufficient to just assess skin exposure to physical and chemical stressors in workplaces, but that it is also important to assess the condition, i.e. skin barrier function of the exposed skin at the time of exposure. The workplace environment, representing a non‐clinical environment, can be highly variable and difficult to control, thereby presenting unique measurement challenges not typically encountered in clinical settings.

Methods

An expert working group convened a workshop as part of the 5th International Conference on Occupational and Environmental Exposure of Skin to Chemicals (OEESC) to develop basic guidelines and best practices (based on existing clinical guidelines, published data, and own experiences) for thein vivomeasurement of transepidermal water loss (TEWL) and skin hydration in non‐clinical settings with specific reference to the workplace as a worst‐case scenario.

Results

Key elements of these guidelines are: (i) to minimize or recognize, to the extent feasible, the influences of relevant endogenous‐, exogenous‐, environmental‐ and measurement/instrumentation‐related factors; (ii) to measureTEWLwith a closed‐chamber type instrument; (iii) report results as a difference or percent change (rather than absolute values); and (iv) accurately report any notable deviations from this guidelines.

Conclusion

It is anticipated that these guidelines will promote consistent data reporting, which will facilitate inter‐comparison of study results.
Stem cell therapy in veterinary dermatology
Authors: Harman Robert J.
Published: January 2013

Background –  Adult stem cells come from many sources and have the capacity to differentiate into many cell types, including those of the skin. The most commonly studied stem cells are those termed mesenchymal stem cells (MSCs), which are easily isolated from bone marrow and adipose tissue. Mesenchymal stem cells are known to produce a wide array of cytokines that modulate the regeneration process. The ease of collection, propagation and use of these MSCs in therapy of traumatic, ischaemic and immune‐mediated skin conditions is emerging.

Approach and evidence –  In traumatic and ischaemic skin damage, MSCs are used in tissue‐engineered skin and by direct injection into damaged tissue. For immune‐mediated diseases, systemic administration of stem cells can modulate the immune system. The earliest clinical work has been with autologous stem cell sources, such as adipose tissue and bone marrow. In immune‐mediated diseases, the MSCs are used to downregulate production of inflammatory cytokines and to block T‐cell activation. Cells are generally given intravenously. Multiple sclerosis, rheumatoid arthritis and lupus have been successfully treated in human clinical trials. Mesenchymal stem cells can also stimulate resident local cells, such as keratinocytes and progenitor cells, to proliferate, migrate and repair skin injury and disease.

Looking ahead –  The discovery of the MSC in adipose tissue has spawned a global effort to utilize these cells in therapy of a wide range of diseases of the skin. Reconstructive surgery, scar blocking and resolution and skin regeneration have all been shown to be possible in human and animal studies.
Sinusoidal high‐intensity exercise does not elicit ventilatory limitation in chronic obstructive pulmonary disease
Authors: Porszasz Janos , Rambod Mehdi , van der Vaart Hester , Rossiter Harry B. , Ma Shuyi , Kiledjian Rafi , Casaburi Richard
Published: January 2013

New Findings

What is the central question of this study?

Is it possible for patients with chronic obstructive pulmonary disease to avoid ventilatory limitation during high‐intensity exercise by using a fast‐fluctuating sinusoidal exercise task?

What is the main finding and its importance?

Sinusoidal exercise, with a cycle time of 60 s superimposed upon a mean work rate at critical power, resulted in minimal fluctuations in the exercise ventilation. Thus, high‐intensity exercise, with excursions well above peak aerobic power, was sustained for up to 20 min in chronic obstructive pulmonary disease patients, and the end‐exercise ventilation was less than peak. This exercise protocol may prove beneficial in rehabilitative exercise training programmes where large gains in skeletal muscle adaptation are the goal.

During exercise at critical power (CP) in chronic obstructive pulmonary disease (COPD) patients, ventilation approaches its maximum. As a result of the slow ventilatory dynamics in COPD, ventilatory limitation during supramaximal exercise might be escaped using rapid sinusoidal forcing. Nine COPD patients [age, 60.2 ± 6.9 years; forced expiratory volume in the first second (FEV1), 42 ± 17% of predicted; and FEV1/FVC, 39 ± 12%] underwent an incremental cycle ergometer test and then four constant work rate cycle ergometer tests; tolerable duration (tlim) was recorded. Critical power was determined from constant work rate testing by linear regression of work rate versus 1/tlim. Patients then completed fast (FS; 60 s period) and slow (SS; 360 s period) sinusoidally fluctuating exercise tests with mean work rate at CP and peak at 120% of peak incremental test work rate, and one additional test at CP; each for a 20 min target. The value of tlim did not differ between CP (19.8 ± 0.6 min) and FS (19.0 ± 2.5 min), but was shorter in SS (13.2 ± 4.2 min; P < 0.05). The sinusoidal ventilatory amplitude was minimal (37.4 ± 34.9 ml min−1 W−1) during FS but much larger during SS (189.6 ± 120.4 ml min−1 W−1). The total ventilatory response in SS reached 110 ± 8.0% of the incremental test peak, suggesting ventilatory limitation. Slow components in ventilation during constant work rate and FS exercises were detected in most subjects and contributed appreciably to the total response asymptote. The SS exercise was associated with higher mid‐exercise lactate concentrations (5.2 ± 1.7, 7.6 ± 1.7 and 4.5 ± 1.3 mmol l−1 in FS, SS and CP). Large‐amplitude, rapid sinusoidal fluctuation in work rate yields little fluctuation in ventilation despite reaching 120% of the incremental test peak work rate. This high‐intensity exercise strategy might be suitable for programmes of rehabilitative exercise training in COPD.
Relevance of vascular peroxisome proliferator‐activated receptor γ coactivator‐1α to molecular alterations in atherosclerosis
Authors: Valero‐Muñoz M. , Martín‐Fernández B. , Ballesteros S. , Martínez‐Martínez E. , Blanco‐Rivero J. , Balfagón G. , Cachofeiro V. , Lahera V. , de las Heras N.
Published: January 2013

New Findings

What is the central question of this study?

Does PGC‐1α play a key role in vascular alterations induced by cholesterol+coconut oil diet in rabbits?

What is the main finding and its importance?

Vascular expression of PGC‐1α, SIRT1 and PPARγ were reduced in atherosclerotic rabbits. Furthermore, PGC‐1α correlated with processes involved in atherosclerosis (endothelial dysfunction, oxidative stress and inflammation). Reduction of PGC‐1α seems to play an important role in the molecular alterations during the development of atherosclerosis.

Peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) is emerging as a novel factor that plays a critical role in integrating signalling pathways in the control of cellular and systemic metabolism. We investigated the role of vascular expression of PGC‐1α and related factors, such as sirtuin 1 (SIRT1), peroxisome proliferator‐activated receptor γ (PPARγ) and adiponectin, during the atherosclerotic process. Endothelial function, vascular superoxide anion production and inflammatory mediators were also evaluated. This study was carried out in male New Zealand rabbits fed a diet containing 0.5% cholesterol and 14% coconut oil for 8 weeks. Animals developed mixed dyslipidaemia and atherosclerotic lesions, which were associated with endothelial dysfunction, aortic overproduction of superoxide anions and inflammation. Expression of PGC‐1α, SIRT1, PPARγ and adiponectin was reduced (P < 0.05) in aorta from atherosclerotic rabbits. Levels of PGC‐1α were correlated negatively (P < 0.05) with total cholesterol levels, aortic superoxide anion production and tumour necrosis factor‐α expression, and positively (P < 0.05) with maximal relaxation in response to acetylcholine. The observed results suggest that PGC‐1α could be considered to be a link between the main atherosclerotic processes (endothelial dysfunction, oxidation and inflammation) and alterations of other factors involved in vascular wall integrity, such as SIRT1, PPARγ and adiponectin.
Combined Intravenous and Intraventricular Administration of Colistin Methanesulfonate in Critically Ill Patients with Central Nervous System Infection
Authors: Ziaka Mairi , Markantonis Sophia L. , Fousteri Marizoza , Zygoulis Paris , Panidis Dimitris , Karvouniaris Marios , Makris Demosthenes , Zakynthinos Epaminondas
Published: January 2013

Colistin pharmacokinetics were prospectively studied after intravenous administration of colistin methanesulphonate in critically ill patients without central nervous system infection (controls,
n
= 5) and in patients with external ventricular drain-associated ventriculitis after intravenous administration (EVDViv,
n
= 3) or combined intravenous/intraventricular administration (EVDVcomb,
n
= 4). Cerebrospinal fluid (CSF)/serum colistin concentration ratios were higher in EVDViv than in control patients (11% versus 7%,
P
≤ 0.05) and in EVDVcomb compared to all other patients (
P
< 0.0001). CSF colistin concentrations above the MIC of 0.5 μg/ml were achieved only in EVDVcomb patients.
Vancomycin AUC/MIC Ratio and 30-Day Mortality in Patients with Staphylococcus aureus Bacteremia
Authors: Holmes Natasha E. , Turnidge John D. , Munckhof Wendy J. , Robinson J. Owen , Korman Tony M. , O'Sullivan Matthew V. N. , Anderson Tara L. , Roberts Sally A. , Warren Sanchia J. C. , Gao Wei , Howden Benjamin P. , Johnson Paul D. R.
Published: January 2013

A ratio of the vancomycin area under the concentration-time curve to the MIC (AUC/MIC) of ≥400 has been associated with clinical success when treating
Staphylococcus aureus
pneumonia, and this target was recommended by recently published vancomycin therapeutic monitoring consensus guidelines for treating all serious
S. aureus
infections. Here, vancomycin serum trough levels and vancomycin AUC/MIC were evaluated in a “real-world” context by following a cohort of 182 patients with
S. aureus
bacteremia (SAB) and analyzing these parameters within the critical first 96 h of vancomycin therapy. The median vancomycin trough level at this time point was 19.5 mg/liter. There was a significant difference in vancomycin AUC/MIC when using broth microdilution (BMD) compared with Etest MIC (medians of 436.1 and 271.5, respectively;
P
< 0.001). Obtaining the recommended vancomycin target AUC/MIC of ≥400 using BMD was not associated with lower 30-day all-cause or attributable mortality from SAB (
P
= 0.132 and
P
= 0.273, respectively). However, an alternative vancomycin AUC/MIC of >373, derived using classification and regression tree analysis, was associated with reduced mortality (
P
= 0.043) and remained significant in a multivariable model. This study demonstrated that we obtained vancomycin trough levels in the target therapeutic range early during the course of therapy and that obtaining a higher vancomycin AUC/MIC (in this case, >373) within 96 h was associated with reduced mortality. The MIC test method has a significant impact on vancomycin AUC/MIC estimation. Clinicians should be aware that the current target AUC/MIC of ≥400 was derived using the reference BMD method, so adjustments to this target need to be made when calculating AUC/MIC ratio using other MIC testing methods.
In Vitro
Antifungal Susceptibility of Clinically Relevant Species Belonging to Aspergillus Section
Flavi
Authors: Gonçalves Sarah S. , Stchigel Alberto M. , Cano Josep , Guarro Josep , Colombo Arnaldo L.
Published: January 2013

The
in vitro
antifungal susceptibility of 77 isolates belonging to different clinically relevant species of
Aspergillus
section
Flavi
, including those of different phylogenetic clades of
A. flavus
, was tested for nine antifungal agents using a microdilution reference method (CLSI, M38-A2). Terbinafine and the echinocandins demonstrated lower MICs/MECs for all species evaluated, followed by posaconazole. Amphotericin B showed MICs ≥ 2 μg/ml for 38 (49.4%) of the 77 isolates tested.
Involvement of Efflux Pumps in the Resistance to Peptidoglycan Synthesis Inhibitors in Mycobacterium tuberculosis
Authors: Dinesh Neela , Sharma Sreevalli , Balganesh Meenakshi
Published: January 2013

We evaluated the contributions of
Mycobacterium tuberculosis
efflux pumps towards intrinsic resistance to different classes of peptidoglycan synthesis inhibitors (PSI). Our study indicates that the efflux pump knockout strains are more susceptible to PSI than the wild type. Vancomycin and ceftriaxone exhibited up to 3 log increased kill on efflux pump mutants compared to the wild-type strain, strongly suggesting an important role for efflux pumps in the intrinsic resistance of
M. tuberculosis
to PSI.
Evaluating 5-Nitrofurans as Trypanocidal Agents
Authors: Bot Christopher , Hall Belinda S. , Álvarez Guzmán , Di Maio Rossanna , González Mercedes , Cerecetto Hugo , Wilkinson Shane R.
Published: January 2013

The nitroheterocycle nifurtimox, as part of a nifurtimox-eflornithine combination therapy, represents one of a limited number of treatments targeting
Trypanosoma brucei
, the causative agent of human African trypanosomiasis. The mode of action of this prodrug involves an initial activation reaction catalyzed by a type I nitroreductase (NTR), an enzyme found predominantly in prokaryotes, leading to the formation of a cytotoxic unsaturated open-chain nitrile metabolite. Here, we evaluate the trypanocidal activities of a library of other 5-nitrofurans against the bloodstream form of
T. brucei
as a preliminary step in the identification of additional nitroaromatic compounds that can potentially partner with eflornithine. Biochemical screening against the purified enzyme revealed that all 5-nitrofurans were effective substrates for
T. brucei
NTR (TbNTR), with the preferred compounds having apparent
k
cat
/

K
m

values approximately 50-fold greater than those of nifurtimox. For several compounds,
in vitro
reduction by this nitroreductase yielded products characterized by mass spectrometry as either unsaturated or saturated open-chain nitriles. When tested against the bloodstream form of
T. brucei
, many of the derivatives displayed significant growth-inhibitory properties, with the most potent compounds generating 50% inhibitory concentrations (IC
50
s) around 200 nM. The antiparasitic activities of the most potent agents were demonstrated to be NTR dependent, as parasites having reduced levels of the enzyme displayed resistance to the compounds, while parasites overexpressing TbNTR showed hypersensitivity. We conclude that other members of the 5-nitrofuran class of nitroheterocycles have the potential to treat human African trypanosomiasis, perhaps as an alternative partner prodrug to nifurtimox, in the next generation of eflornithine-based combinational therapies.
Selective Serotonin Reuptake Inhibitor Fluoxetine Inhibits Replication of Human Enteroviruses B and D by Targeting Viral Protein 2C
Authors: Ulferts Rachel , van der Linden Lonneke , Thibaut Hendrik Jan , Lanke Kjerstin H. W. , Leyssen Pieter , Coutard Bruno , De Palma Armando M. , Canard Bruno , Neyts Johan , van Kuppeveld Frank J. M.
Published: January 2013

Although the genus
Enterovirus
contains many important human pathogens, there is no licensed drug for either the treatment or the prophylaxis of enterovirus infections. We report that fluoxetine (Prozac)—a selective serotonin reuptake inhibitor—inhibits the replication of human enterovirus B (HEV-B) and HEV-D but does not affect the replication of HEV-A and HEV-C or human rhinovirus A or B. We show that fluoxetine interferes with viral RNA replication, and we identified viral protein 2C as the target of this compound.
Pharmacokinetics of Anidulafungin in Critically Ill Patients with Candidemia/Invasive Candidiasis
Authors: Liu Ping , Ruhnke Markus , Meersseman Wouter , Paiva José Artur , Kantecki Michal , Damle Bharat
Published: January 2013

The pharmacokinetics of intravenous anidulafungin in adult intensive care unit (ICU) patients were assessed in this study and compared with historical data from a general patient population and healthy subjects. Intensive plasma sampling was performed over a dosing interval at steady state from 21 ICU patients with candidemia/invasive candidiasis. All patients received the recommended dosing regimen (a 200-mg loading dose on day 1, followed by a daily 100-mg maintenance dose), except for a 54-year-old 240-kg female patient (who received a daily 150-mg maintenance dose instead). Plasma samples were assayed for anidulafungin using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters in ICU patients were calculated by a noncompartmental method. With the exclusion of the 240-kg patient, the median (minimum, maximum) age, weight, and body mass index (BMI) of 20 ICU patients were 57 (39, 78) years, 65 (48, 106) kg, and 23.3 (16.2, 33.8) kg/m
2
, respectively. The average anidulafungin area under the curve over the 24-hour dosing interval (AUC
0-24
), maximum concentration (
C
max
), and clearance (CL) in 20 ICU patients were 92.7 mg · h/liter, 7.7 mg/liter, and 1.3 liters/h, respectively. The exposure in the 240-kg patient at a daily 150-mg dose was within the range observed in ICU patients overall. The average AUC
0-24
and
C
max
in the general patient population and healthy subjects were 110.3 and 105.9 mg · h/liter and 7.2 and 7.0 mg/liter, respectively. The pharmacokinetics of anidulafungin in ICU patients appeared to be comparable to those in the general patient population and healthy subjects at the same dosing regimen.
Virus Susceptibility Analyses from a Phase IV Clinical Trial of Inhaled Zanamivir Treatment in Children Infected with Influenza
Authors: Yates Phillip J. , Mehta Nalini , Horton Joseph , Tisdale Margaret
Published: January 2013

A zanamivir postapproval efficacy study was conducted in children (n= 279) in Japan during three influenza seasons. Pharyngeal swab specimens (n= 714) were obtained for detailed resistance analysis. From 371 cultured viruses, 3 viruses (A/H1N1) from two subjects showed reduced susceptibility to zanamivir at day 1 (before treatment), 1 had an N74S amino acid substitution (fold shift, 46), and 2 (day 1 and day 2) had a Q136K amino acid substitution (fold shifts, 292 and 301). Q136K was detected only in cultured virus and not in the swab. From the remaining 118 cultured viruses obtained during or after treatment with zanamivir, no shifts in virus susceptibility were detected. Neuraminidase (NA) population sequencing showed that viruses from 12 subjects had emergent amino acid substitutions, but 3 with susceptibility data were not zanamivir resistant. The remainder may be natural variants. Further analysis is planned. Hemagglutinin (HA) sequencing showed that viruses from 20 subjects had 9 HA amino acid substitutions that were previously implicated in resistance to neuraminidase inhibitors inin vitroassays or that were close to the receptor binding site. Their role inin vivoresistance appears to be less important but is not well understood. NA clonal sequence analysis was undertaken to determine if minority species of resistant viruses were present. A total of 1,682 clones from 90 subjects were analyzed. Single clones from 12 subjects contained amino acid substitutions close to the NA active site. It is unclear whether these single amino acid substitutions could have been amplified after drug pressure or are just chance mutations introduced during PCR.