bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi‐scale habitat selection of Mus minutoides in the Lowveld of Swaziland
Authors: Long Andrea K. , Bailey Karen , Greene Daniel U. , Tye Courtney , Parr Courtnee , Lepage Heather K. , Gielow Kurt H. , Monadjem Ara , McCleery Robert A.
Published: December 2012

We investigated habitat selection of Mus minutoides in northeastern Swaziland. We used powder tracking to determine how M. minutoides selected habitat at a fine scale and a broader path scale. At the fine scale, we measured per cent cover of grass and shrubs, the number of forbs and visual obstruction (VO) at five evenly spaced points along a mouse's pathway and at a paired random location. At the path scale, we calculated the relative displacement (RD) of each path as the ratio of the distance from the start to the end point of the path to the total length of the path (values near one indicate less preference). We found that M. minutoides were positively associated with increases in visual obstruction, grass cover, and shrub cover at the fine scale, but not at the path scale. Our results indicate that M. minutoides selection of vegetative features at the path scale is not as important as their fine‐scale selection of vegetative structure. In addition, the shrub encroachment on our study site may be directly beneficial to M. minutoides at the fine scale. Our results provide us with an increased understanding of the basic ecology of M. minutoides and information on their response to a changing landscape.
Uptake to HIV Post‐Exposure Prophylaxis in Haiti: Opportunities to Align Sexual Violence, HIV PEP and Mental Health
Authors: Marc Linda , Honoré Jean‐Guy , Néjuste Patrick , Setaruddin Monica , Lamothe Nika‐Nola , Thimothé Gabriel , Cornely Jean‐Ronald
Published: December 2012

Sexual violence is a public health problem in Haiti, potentially augmenting HIV transmission. Reports from L'Hôpital de l'Université d'État d'Haiti (HUEH) suggest severe underutilization of antiretroviral post‐exposure prophylaxis (ARV‐PEP) among rape survivors. Cross‐sectional design using mixed methods. Informational interviews were conducted with HUEH personnel to learn about post‐rape service offerings. HUEH surveillance data were used to estimate the sexual assault reporting rate/100,000 and to examine the proportion of survivors receiving ARV‐PEP within 72 hr, stratified by age (<18 years, ≥18 years). Informational interviews revealed that survivors were navigated through two hospital algorithms to receive post‐rape care; however, <5% of victims sought mental health services. Surveillance data show that 2193 sexual assault survivors (adult and pediatric) reported a rape to HUEH personnel between 2004 through first quarter of 2010. Annual estimates suggest a twofold increase comparing cases in 2004 versus 2009. Between 2008 and 2009, uptake to ARV‐PEP within 72 hr was lower for pediatric (38.4%; N = 131/341) compared with adult survivors (60.1%; N = 83/138) (χ2 = 18.8, P < 0.001). The prioritization of funding and comprehensive interventions that align sexual violence, HIV, and mental health is crucial to support the timely uptake to ARV‐PEP.
The paediatric consequences of Assisted Reproductive Technologies, with special emphasis on multiple pregnancies
Authors: Barrington Keith J , Janvier Annie
Published: December 2012

Paediatricians will encounter many babies and children who are the result of assisted reproductive technologies. Although in most cases, there are no adverse health consequences, assisted reproductive technologies (ART) are associated with some risks that are reviewed in this article.

Conclusion

ART has had a major impact on multiple gestation and the incidence of prematurity in many countries. Among singletons, there are also increases in prematurity, small for gestational age, congenital anomalies and perinatal mortality.
Effect of geomorphology and nitrogen deposition on rate of vegetation succession in inland drift sands
Authors: Sparrius Laurens B. , Kooijman Annemieke M. , Riksen Michel P.J.M. , Sevink Jan
Published: December 2012

Questions

(1) At what rate does succession take place in active and more stabilized drift sands in regions with low and highNdeposition in theNetherlands? (2) What is the present composition of pioneer vegetation in active and more stabilized drift sands in regions with low and highNdeposition? (3) What efforts are necessary to conserve bare sand in drift sands?

Location

Eight inland dunes in theNetherlands, which represent four active and four more stabilized drift sands in regions with low and high N deposition.

Methods

Aerial photographs from 1950, 1981, 1995 and 2007 were used to compare rates of succession from bare sand towards forest. For each site, a detailed vegetation map was made in 2007.

Results

In all studied sites, bare sand decreased, especially in regions with highNdeposition. This decline was significantly higher between 1981 and 2007 than between 1950 and 1981. The loss of bare sand did not lead to an increase of pioneer vegetation, which remained more or less stable; it led, however, to an increase of heath and forest. In active drift sands, pioneer vegetation was characterized byCorynephorus canescensandPolytrichum piliferum, while lichens, lichen‐rich grassland andCampylopus introflexuswere more common in stabilized drift sands. In regions with highNdeposition, the proportion ofCampylopus introflexusto older pioneer stages was significantly higher, and the contribution of forest to the ‘heath/forest’ vegetation class was also higher. The calculated life span of bare sand decreased in all sites. Extrapolation of the results suggests that in the absence of restoration measures, bare sand will vanish by 2035.

Conclusions

In both active and more stabilized drift sands, a generic loss of bare sand and an increase in forest area was found. The increase was higher in regions with highNdeposition. Conservation management should include the annual transformation of 43 ha of forest into bare sand in order to stop the loss of bare sand.
A morphological, morphometric and histochemical study of the oviduct in pregnant and non‐pregnant females of the plains viscacha (Lagostomus maximus)
Authors: Flamini Mirta A. , Barbeito Claudio G. , Portiansky Enrique L.
Published: December 2012

The oviduct is a very thin organ with a very tortuous appearance. It is divided into three segments: the infundibulum, the ampulla and the isthmus. Particularly, the oviduct of the viscacha lacks the intramural portion described in other species. The mucosa shows longitudinal pleats. The free edge of the infundibulum ends as small fimbriae that are of variable length and do not completely cover the ovary. The proportion of ciliated and secretory epithelial cells varied both in relation to the segments of the oviduct analysed and to the physiological state (anoestrus, follicular phase, early pregnancy and late pregnancy). The glycocalix and the apical region of the superficial epithelial cells arePASand alcian‐blue positive. The muscular layers vary in thickness in different regions. Some lectins such asUEA‐1 andDBAshowed variations in the binding pattern during the different physiological stages analysed whereasRCA‐1andWGAhad a very stable pattern.
Sexual dimorphism in histological characteristics and contractility of the iliofibularis muscle in the lizard Sceloporus torquatus
Authors: Quintana Erendira , Manjarrez Javier , Martínez‐Gómez Margarita , D'Alba Liliana , Rodríguez‐Antolín Jorge , Fajardo Victor
Published: December 2012

The iliofibularis is a hindlimb muscle used in lizard locomotion that is composed of at least three types of fibres: fast‐twitch‐glycolytic (FG), fast‐twitch‐oxidative‐glycolytic fibre (FOG) and slow‐twitch‐oxidative (SO). The striated skeletal muscle is a highly plastic tissue undergoing phenotypic change in response to activity. The lizard Sceloporus torquatus has sexual differences associated with microhabitat use, which can be reflected in the physiology and anatomy of the muscle, and thus, in our study, we analysed the morphological and contractile characteristics of the iliofibularis muscle (IF) of S. torquatus males and females. We found a larger prevalence of FOG compared with FG and SO fibres in the muscle of both sexes. We also found that males show larger areas of the three types of fibres, develop greater strength but also faster fatigue than females, suggesting that strength is a key functional feature that enables males to perform faster movements (but for shorter periods), associated with the demands of territoriality.
Evaluation of nevirapine dosing recommendations in HIV‐infected children
Authors: Foissac Frantz , Bouazza Naïm , Frange Pierre , Blanche Stéphane , Faye Albert , Lachassinne Eric , Dollfus Catherine , Hirt Déborah , Benaboud Sihem , Treluyer Jean‐Marc , Urien Saïk
Published: December 2012

Aims

Nevirapine (NVP) is a non‐nucleoside reverse transcriptase inhibitor used for chronic human immunodeficiency virus infections in adults and children. The aims of this study were to investigate the population pharmacokinetics of NVP in children, establish factors that influence NVP pharmacokinetics and evaluate the current dosing recommendations.

Methods

Concentrations were measured on a routine basis in 94 children aged from 2 months to 17 years. A total of 390 NVP plasma concentrations were retrospectively collected, and a population pharmacokinetic model was developed with Monolix 4.0.

Results

Nevirapine pharmacokinetics was best described by a one‐compartment model with first‐order absorption and elimination. After standardization to a 70 kg adult using allometry, postmenstrual age had a significant effect on the bioavailability. Estimates of apparent clearance and volume of distribution were 3.9 l h−1 (70 kg)−1 and 140 l (70 kg)−1, respectively. Based on simulations of European Medicines Agency (EMA) and World Health Organization (WHO) dosing recommendations, the probability of observing minimal concentrations below the efficacy target of 3 mg l−1 is higher following the EMA recommendations than the WHO recommendations. However, NVP underdosing persists for the 3–6 and 6–10 kg weight ranges following the WHO recommendations.

Conclusions

It is suggested to increase doses to 75 and 100 mg twice daily for the 3–6 and 6–10 kg weight ranges, respectively, in order to obtain more than 95% of children with concentrations above 3 mg l−1.
Iron chelation: a potential therapeutic strategy in oesophageal cancer
Authors: Keeler BD , Brookes MJ
Published: December 2012

Raised intracellular iron has been identified as a potential aetiological factor in the development of several epithelial malignancies, including those of the gastrointestinal tract. The mechanism behind this increase is thought to include disorders of iron uptake and storage. Several iron chelators have been identified as potential anti‐tumour agents, with much work undertaken to ascertain the exact mode of action. Despite this, there is little known about the role that these drugs play in the cellular iron metabolism of oesophageal cancer. Consequently, the present study looks to review the relationship of two clinically important iron‐chelating agents, deferoxamine and deferasirox, on cellular iron uptake and storage in oesophageal squamous and adenocarcinoma. This provides important evidence for the debate about the role these agents have in the clinical management of such tumours.

Linked Article

This article is a commentary on Ford et al., pp. 1316–1328 of this issue. To view this paper visit http://dx.doi.org/10.1111/bph.12045
Olesoxime protects embryonic cortical neurons from camptothecin intoxication by a mechanism distinct from BDNF
Authors: Gouarné Caroline , Giraudon‐Paoli Marc , Seimandi Mathieu , Biscarrat Clotilde , Tardif Gwenaëlle , Pruss Rebecca M , Bordet Thierry
Published: December 2012

Background and Purpose

Olesoxime is a small cholesterol–oxime promoting rat embryonic motor neurons survival in the absence of trophic factors. Because olesoxime can substitute for neurotrophic factors in many situations, and to gain further understanding of its mechanism of action, we wondered if it could prevent neuronal death induced by camptothecin (CPT) and compared its effects with those of brain‐derived neurotrophic factor (BDNF).

Experimental Approach

E17 rat embryonic cortical neurons were treated with olesoxime, BDNF or vehicle and intoxicated with CPT. Caspase‐dependent and caspase‐independent death pathways along with pro‐survival pathways activation were explored.

Key Results

As previously reported for BDNF, olesoxime dose‐dependently delayed CPT‐induced cell death. Both compounds acted downstream of p53 activation preventing cytochrome c release and caspases activation. When caspase activation was blocked, both olesoxime and BDNF provided additional neuroprotective effect, potentially through the prevention of apoptosis‐inducing factor release from mitochondria. While BDNF activates both the PI3K/Akt and the ERK pathway, olesoxime induced only a late activation of the ERK pathways, which did not seem to play a major role in its neuroprotection against CPT. Rather, our results favour preserved mitochondrial membrane integrity by olesoxime.

Conclusions and Implications

Albeit different, olesoxime and BDNF mechanisms for neuroprotection converge to preserve mitochondrial function. These findings emphasize the importance of targeting the mitochondria in the process of neurodegeneration. Importantly olesoxime, by mimicking neurotrophin pro‐survival activities without impacting PI3K/Akt and ERK signalling, may have greater therapeutic potential in many diseases where neurotrophins were considered as a therapeutic solution.
Cardiac characterization of 16 patients with large NF1 gene deletions
Authors: Nguyen R , Mir TS , Kluwe L , Jett K , Kentsch M , Mueller G , Kehrer‐Sawatzki H , Friedman JM , Mautner V‐F
Published: December 2012

The aim of this study was to characterize cardiac features of patients with neurofibromatosis 1 (NF1) and large deletions of the NF1 gene region. The study participants were 16 patients with large NF1 deletions and 16 age‐ and sex‐matched NF1 patients without such deletions. All the patients were comprehensively characterized clinically and by echocardiography. Six of 16 NF1 deletion patients but none of 16 non‐deletion NF1 patients have major cardiac abnormalities (p = 0.041). Congenital heart defects (CHDs) include mitral insufficiency in two patients and ventricular septal defect, aortic stenosis, and aortic insufficiency in one patient each. Three deletion patients have hypertrophic cardiomyopathy. Two patients have intracardiac tumors. NF1 patients without large deletions have increased left ventricular (LV) diastolic posterior wall thickness (p < 0.001) and increased intraventricular diastolic septal thickness (p = 0.001) compared with a healthy reference population without NF1, suggestive of eccentric LV hypertrophy. CHDs and other cardiovascular anomalies are more frequent among patients with large NF1 deletion and may cause serious clinical complications. Eccentric LV hypertrophy may occur in NF1 patients without whole gene deletions, but the clinical significance of this finding is uncertain. All patients with clinical suspicion for NF1 should be referred to a cardiologist for evaluation and surveillance.
Self‐Management Intervention to Improve Self‐Care and Quality of Life in Heart Failure Patients
Authors: Tung Heng‐Hsin , Lin Chun‐Yu , Chen Kuei‐Ying , Chang Chien‐Jung , Lin Yu‐Ping , Chou Cheng‐Hui
Published: December 2012

Self‐management intervention is a good method to improve self‐care ability, as such, to promote quality of life. However, the research focused on self‐management intervention in heart failure patients in Taiwan is very limited. Therefore, the purposes of this study were to test the effectiveness of self‐management intervention in patients with heart failure in Taiwan and examine the relationship between self‐care ability and quality of life. A quasi‐experimental design was used in this study with convenience sampling. Of the 82 subjects participating in this study, 40 of them chose to join the experimental (self‐management intervention plus usual care) and 42 of them chose to join control (usual care) group. Three questionnaires were used to collect the data, which were the demographic questionnaire, the self‐care questionnaire (Self‐Care of HF Index V 6), and the quality of life questionnaire (Minnesota Living with Heart Failure Questionnaire). To examine the effectiveness of the intervention, self‐care ability and quality of life were measured, using a pretest, 1‐ and 2‐month follow‐up assessment. Generalized estimation equations (GEE) were used to compare changes over time among groups for outcomes to ensure the effectiveness of the intervention. This study confirmed the effectiveness of the self‐management intervention. The clinical provider should increase the awareness of the importance of self‐management skills and self‐care ability especially for heart failure patients. The designated disease‐specific self‐management patient book and individualize intervention should be dispensing and implementing.
Characterization and Prediction of Natriuretic Peptide “Nonresponse” During Heart Failure Management: Results From the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) and the NT‐proBNP–Assisted Treatment to Lessen Serial Cardiac Readmissions and Death (BATTLESCARRED) Study
Authors: Gaggin Hanna K. , Truong Quynh A. , Rehman Shafiq U. , Mohammed Asim A. , Bhardwaj Anju , Parks Kimberly A. , Sullivan Dorothy A. , Chen‐Tournoux Annabel , Moore Stephanie A. , Richards A. Mark , Troughton Richard W. , Lainchbury John G. , Weiner Rory B. , Baggish Aaron L. , Semigran Marc J. , Januzzi James L.
Published: December 2012

Many proven heart failure (HF) therapies decrease N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) values over time, yet some patients have an NT‐proBNP >1000 pg/mL following treatment, which is associated with poor outcomes. A total of 151 patients with left ventricular systolic dysfunction were treated with aggressive HF therapy in the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study. Clinical characteristics and NT‐proBNP were measured at each visit during 10 months. In this post hoc analysis, biomarker nonresponse was defined as an NT‐proBNP >1000 pg/mL and its relationship with echocardiographic and clinical characteristics and outcomes were explored. A risk model predictive of nonresponse was derived and externally validated. A rising NT‐proBNP over time was associated with increased cardiovascular event rates while a decreasing NT‐proBNP was associated with better clinical outcomes (58.2% vs 27.6%, P=.001). A higher percentage of time in biomarker response was associated with lower event rates (P<.001). Importantly, responders showed improved left ventricular remodeling parameters (all P<.001), while nonresponders did not. A risk model for predicting nonresponse had a C statistic of 0.82 (P<.001) and predicted outcomes well. Using data from the NT‐proBNP–Assisted Treatment to Lessen Serial Cardiac Readmissions and Death (BATTLESCARRED) cohort, the risk score was validated for its ability to predict nonresponse (C statistic 0.73, P<.001). Serial changes in NT‐proBNP inform risk for adverse outcome and are associated with prognostically meaningful metrics. Prediction of future NT‐proBNP nonresponse to HF therapy is possible.
Remote Care Costs for Congestive Heart Failure: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials in the United States Comparing Remote Versus More Intensive Care Settings
Authors: Voigt Jeffrey , Mosier Michael
Published: December 2012

It has been assumed that less intense levels of care for managing heart failure result in a lowering of the overall costs for this care in the United States. The objective of this review was to determine whether this assumption is correct. A systematic review was performed using Medline, technology assessment Web sites, and relevant cardiovascular and heart failure journals from the year 2000 to the present. US randomized controlled trials where costs were evaluated as one of the endpoints were included. Data were collected using Cochrane Review characteristics of included studies and risk of bias assessment forms. Cost data from each trial were converted to a uniform cost definition and year. Meta‐analysis was performed where appropriate. Ten trials were identified evaluating costs at various time points (3, 6, and 12 months). Meta‐analysis of trials demonstrated no difference in costs for care, no matter the patient condition or settings. In high‐quality trials examining costs, there may be a shifting in costs from more expensive care settings to less expensive care settings without savings to the healthcare system. Larger and longer‐term trials should be undertaken to understand this issue.
A combined test of acetylcholine‐mediated vasodilation of both the forearm resistance vessels and the radial artery
Authors: Lind Lars
Published: December 2012

Objective

To evaluate a new combined test of endothelium‐dependent vasodilation (EDV) in the forearm resistance vessel and the radial artery.

Methods

Acetylcholine (ACh) and sodium nitroprusside (SNP) infusion in the brachial artery were used to simultaneous evaluate EDV and endothelium‐independent vasodilation (EIDV) in forearm resistance vessels (plethysmography) and in the radial artery (ultrasound) in 76 healthy subjects. Brachial artery ultrasound was used to assess flow‐mediated vasodilation (FMD).

Results

Acetylcholine induced a 4·5% (median value, P = 0·0010) increase in the radial artery diameter, while SNP induced a 31·2% increase in diameter (P<0·0001). While no increase in radial artery blood flow was induced by ACh (P = 0·69), an increase by 181% in radial blood flow was induced by SNP (P<0·0001).

When relating the radial artery diameter data to FMD, the change in radial artery diameter induced by ACh was significantly correlated with FMD (r = 0·35, P = 0·013). No such relationship was seen for the diameter change induced by SNP (r = −0·03, P = 0·81).

When relating the radial artery blood flow data to EDV and EIDV, the change in radial artery blood flow induced by ACh was significantly correlated with EDV in an inverse fashion (r = −0·42, P = 0·0032). No such relationship was seen for the blood flow change induced by SNP when related to EIDV (r = −0·07, P = 0·63).

Conclusion

Simultaneous measurements of blood flow in forearm vessels by plethysmography and in the radial artery by ultrasound during ACh infusion is a new way to assess EDV in both resistance and conduit arteries during one investigation.
High readmission rates are associated with a significant economic burden and poor outcome in patients with grade III/IV acute GvHD
Authors: Dignan Fiona L. , Potter Mike N. , Ethell Mark E. , Taylor Matthew , Lewis Lily , Brennan Joy , McNamara Louise , Evans Steve O. , Riley Unell , Davies Faith E. , Dearden Claire E. , Morgan Gareth J. , Shaw Bronwen E.
Published: December 2012

Graft‐versus‐host disease (GvHD) is a common complication following haematopoietic stem cell transplant but little is published about the impact of this condition on hospital readmission rates. We report a retrospective analysis of readmission rates and associated costs in 187 consecutive allogeneic transplant patients to assess the impact of GvHD. The overall readmission rate was higher in patients with GvHD (86% (101/118) vs. 59% (41/69), p < 0.001). The readmission rate was higher both in the first 100 d from transplant (p = 0.02) and in the first year following transplant (p < 0.001). 151/455 (33%) of all readmission episodes occurred within 100 d of transplant. The mean number of inpatient days was significantly higher in patients with grade III/IV acute GvHD (101 d) compared with those with grade I/II GvHD (70 d; p = 0.003). The mean cost of readmission was higher in patients with GvHD (£28 860) than in non‐GvHD patients (£13 405; p = 0.002) and in patients with grade III/IV GvHD (£40 012) compared with those patients with grade I/II GvHD (£24 560; p = 0.038). Survival was higher in those with grade I/II GvHD (55%) compared to grade III/IV GvHD (14%; p < 0.001). This study shows the high economic burden and poor overall survival associated with grade III/IV GvHD.
Gastric bypass in Type 2 diabetes with BMI < 30: weight and weight loss have a major influence on outcomes
Authors: Dixon J. B. , Hur K.‐Y. , Lee W.‐J. , Kim M.‐J. , Chong K. , Chen S.‐C. , Straznicky N. E. , Zimmet P.
Published: December 2012

Aim

To assess factors influencing glycaemic control following gastric bypass surgery in patients with Type 2 diabetes and BMI< 30 kg/m2.

Methods

Prospective longitudinal study of 103 patients with inadequate glycaemic control who underwent gastric bypass surgery at Soonchunhyang University, Seoul, Korea (n = 66) and Min‐Sheng General Hospital, Taipei, Taiwan (n = 37). Procedures were performed August 2009 to January 2011. Key outcome measures were excellent glycaemic control of Type 2 diabetes defined as HbA1c < 42 mmol/mol (≤6%); inadequate response defined as HbA1c > 53 mmol/mol (> 7%). Analysis was conducted using binary logistic regression, and cut‐points obtained from receiver operator characteristics.

Results

Excellent glycaemic control was achieved in 31 (30%) at 1 year. Diabetes duration of < 7 years and BMI > 27 kg/m2 provided independent predictors and useful cut‐points. Likelihood of excellent glycaemic control for an individual could be estimated using loge (Odds) = –6.7 + (0.26 × BMI) + (–1.2 × diabetes duration). Baseline BMI of < 27 kg/m2 and baseline C‐peptide of < 2.0ng/ml, best predicted a poor glycaemic response. In those with favourable baseline characteristics percentage weight loss (%WL) had a dominant influence on glycaemic outcomes. Baseline C‐peptide (> 2.4 ng/ml) and subsequent percentage weight loss (> 16%) were associated with excellent glycaemic control. Higher BMI was associated with greater percentage weight loss.

Conclusion

In patients with Type 2 diabetes and BMI < 30 kg/m2, glycaemic response to gastric bypass is predicted by higher baseline BMI, shorter disease duration and higher fasting C‐peptide. Post‐surgery weight loss has a dominant effect. Baseline BMI and weight loss have a major influence on outcomes.
Slow cortical potentials capture decision processes during temporal discounting
Authors: Oswald Felix , Sailer Uta
Published: December 2012

Various neuroimaging studies have detected brain regions involved in discounting the value of temporally delayed rewards. This study used slow cortical potentials (SCPs) to elaborate the time course of cognitive processing during temporal discounting. Depending on their strength of discounting, subjects were categorised as low and high impulsive. Low impulsives, but not high impulsives, showed faster reaction times for making decisions when the delayed reward was of high amount than when it was of low amount. Both low impulsives and high impulsives chose the delayed reward more often when its amount was high than when it was low, but this behavior was more pronounced for low impulsives. Moreover, only low impulsives showed more negative SCPs for low than for high amounts. All three measures indicated that only low impulsives experienced extended conflict for delayed low amounts than for high amounts. Additionally, the SCPs of low impulsives were more sensitive to the delay of the delayed reward than those of high impulsives, extending seconds after the response. This indicates that they continued evaluating their choices even after the decision. Altogether, the present study demonstrated that SCPs are sensitive to decision‐related resource allocation during inter‐temporal decision‐making. Resource allocation depended both on the choice situation and on impulsivity. Furthermore, the time course of SCPs suggested that decision‐related processes occurred both prior to and after the response.
Ceramides stimulate caspase‐14 expression in human keratinocytes
Authors: Jiang Yan J. , Kim Peggy , Uchida Yoshikazu , Elias Peter M. , Bikle Daniel D. , Grunfeld Carl , Feingold Kenneth R.
Published: December 2012

Caspase‐14 is an enzyme that is expressed predominantly in cornifying epithelia and catalyses the degradation of profilaggrin. Additionally, caspase‐14 plays an important role in the terminal differentiation of keratinocytes. However, how caspase‐14 expression is regulated remains largely unknown. Here we demonstrate that ceramides (C2‐Cer and C6‐Cer), but not other sphingolipids (C8‐glucosylceramides, sphinganine, sphingosine‐1‐phosphate or ceramide‐1‐phosphate), increase caspase‐14 expression (mRNA and protein) in cultured human keratinocytes in a dose‐ and time‐dependent manner. Inhibitors of glucosylceramide synthase and ceramidase increase endogenous ceramide levels and also increase caspase‐14 expression, indicating an important regulatory role for ceramides and suggesting that the conversion of ceramides to other metabolites is not required. The increase in caspase‐14 expression induced by ceramides is first seen at 16 h and requires new protein synthesis, suggesting that the ceramide‐induced increase is likely an indirect effect. Furthermore, ceramides increase caspase‐14 gene expression primarily by increasing transcription. Blocking de novo synthesis of ceramides does not affect caspase‐14 expression, suggesting that basal expression is not dependent on ceramide levels. These studies show that ceramides, an important structural lipid, stimulate caspase‐14 expression providing a mechanism for coordinately regulating the formation of lipid lamellar membranes with the formation of corneocytes.
In vivo imaging reveals selective PPAR activity in the skin of peroxisome proliferator‐activated receptor responsive element‐luciferase reporter mice
Authors: El‐Jamal Noura , Dubuquoy Laurent , Auwerx Johan , Bertin Benjamin , Desreumaux Pierre
Published: December 2012

Peroxisome proliferator‐activated receptors (PPARs) have been revealed as key regulators of several skin disorders. This has led to a growing interest in the development of drugs targeting PPARs as therapeutics for skin diseases. To evaluate skin PPAR activity, we developed peroxisome proliferator responsive element‐luciferase (PPRE‐Luc) mice, a mouse model in which the luciferase gene expression is under the control of a PPAR‐inducible promoter in all organs. Our aim was to define and validate experimental conditions to establish PPRE‐Luc mice as a valuable tool for in vivo non‐invasive evaluation of PPARs activation in the skin. We demonstrated by optical imaging that topical application of 40 mm of Luciferin for 10 min was enough to reveal the optimal luciferase activity in mice skin. The treatment of mice skin with the PPARγ and PPARα agonists, pioglitazone and WY14643, was associated with significant increase in photons emission reaching maximal signalling at 6 h. We have performed dose response studies by testing a large range of pioglitazone and WY14643 concentrations on mouse skin. The specificity of bioluminescence signal induced by pioglitazone and WY14643 was assessed using PPARγ and PPARα antagonists, GW9662 and GW6471, respectively. This approach revealed that the isoform specificity of PPARs agonists decreased when high ligand concentrations were applied on mouse skin. These results were further confirmed by in vitro measurement of luciferase activity in skin extracts. Overall, our results demonstrated that PPRE‐Luc mice represent a valuable reporter mouse model for the in vivo pharmacological profiling of drugs targeting PPARs in the skin.
Analysis of moment structures for assessing relationships among perceived chewing ability, dentition status, muscle strength, and balance in community‐dwelling older adults
Authors: Moriya Shingo , Notani Kenji , Murata Ayumi , Inoue Nobuo , Miura Hiroko
Published: December 2012

Objective

The aim of this study was to assess relationships among perceived chewing ability, dentition status, muscle strength and balance in community‐dwelling older adults using analysis of moment structures (Amos).

Background

Physical performance parameters such as muscle strength and balance can predict the future onset of disabilities in activities of daily living among older adults. In this context, elucidation of the relationships among oral conditions and physical performance parameters is necessary.

Materials and methods

Data on occlusal contact patterns of natural teeth (OPNT), self‐assessed masticatory ability (mastication), body mass index (BMI), handgrip strength (HG) and one‐leg standing time with eyes open (OLST) were collected from 501 independently living adults aged 65–74 years. The relationships among these parameters were analysed using Spearman's rank correlation coefficients and Amos.

Results

Subjects of both genders showed significant correlations among OPNT, mastication, HG and OLST, evaluated using Spearman's rank correlation coefficients. For each Amos model, the goodness‐of‐fit statistic indicated a good level of fit. In both men and women, OPNT was significantly related to mastication, and mastication was related to HG but not to OLST. OPNT was related to neither HG nor OLST in women and was related to OLST but not HG in men.

Conclusion

The findings observed in this study present a possible importance of dental status and perceived chewing ability for the onset of disability by influencing physical performance in community‐dwelling older adults.
Measuring excreta patch distribution in grazed pasture through low‐cost image analysis
Authors: Dennis S.J. , Moir J.L. , Cameron K.C. , Edwards G.R. , Di H.J.
Published: December 2012

Nutrient losses from grazed pasture are an important non‐point source of water pollution. The distribution of animal urine patches on pasture is an important factor in determining nitrate losses and influencing pasture growth, nutritive value and pasture acceptability to livestock, as a high amount of nitrogen (N) is deposited onto a small area of soil under a urine patch. Urine distribution may be recorded during or post‐grazing. Measurements during grazing have been automated, but post‐grazing measurement currently relies on manual observations that are time consuming and cannot be subsequently verified. To automate post‐grazing measurements, aerial photographs were taken of grazed pasture approximately 14 d post‐grazing using a standard digital camera. Pasture response areas were successfully identified by analysing the hue of the images using readily available software, yielding comparable results to manual counts. The majority of dung patches did not produce observable pasture responses, with only 14% of the visible response areas being associated with dung, so although this method cannot distinguish between urine and dung response areas, it is primarily influenced by urine. Provided photographs are taken in full sunlight with a high‐quality camera, excreta patch numbers, areas and spatial distribution can be measured with a high degree of precision. Furthermore, the method is relatively inexpensive and applicable to a wide range of situations. A permanent photographic record of the pasture is also established, which allows verification of the analysis in future.
‘Someone should oversee it’: patient perspectives on the ethical issues arising with the regulation of probiotics
Authors: Harrison Krista L. , Farrell Ruth M. , Brinich Margaret A. , Highland Janelle , Mercer MaryBeth , McCormick Jennifer B. , Tilburt Jon , Geller Gail , Marshall Patricia , Sharp Richard R.
Published: December 2012

Background

Although many probiotic products are currently available in yogurt or pill form in the United States (US), there is uncertainty surrounding the structure of regulation of these products. As more therapeutic probiotics are developed, changes to existing regulatory process in the United States may be required to meet the needs of patients and users in the population.

Objective

This study examined how patients with chronic gastrointestinal (GI) diseases view the regulation of probiotics.

Design

We conducted a multi‐site qualitative study consisting of focus groups of patients with chronic gastrointestinal diseases at three tertiary hospitals: at [institutions removed for blinded review].

Results

We conducted 22 focus groups with 136 patients with major gastrointestinal (GI) diseases between March and August 2009. Participants were not familiar with the existing regulation of probiotic products but wanted assurances of accurate labelling of strain as well as safety. Participants raised concerns that regulation of probiotics might be accompanied by greater costs, reduced access and increased involvement of pharmaceutical companies. Although participants voiced significant doubt of government regulators, they felt that products containing genetically modified probiotic strains should have oversight comparable to that of pharmaceutical drugs.

Discussion and conclusion

If GI patient perspectives are indicative of public perceptions of therapeutic probiotics in the United States, consumers may expect more rigorous regulation in the future while simultaneously wanting low costs, easy access and low involvement of pharmaceutical companies. Manufacturers, translational scientists, clinicians and regulators should be sensitive to consumer attitudes when designing, testing and regulating new therapeutic probiotics.
Towards a stakeholders' consensus on patient payment policy: the views of health‐care consumers, providers, insurers and policy makers in six Central and Eastern European countries
Authors: Tambor Marzena , Pavlova Milena , Golinowska Stanisława , Sowada Christoph , Groot Wim
Published: December 2012

Background

Although patient charges for health‐care services may contribute to a more sustainable health‐care financing, they often raise public opposition, which impedes their introduction. Thus, a consensus among the main stakeholders on the presence and role of patient charges should be worked out to assure their successful implementation.

Aim

To analyse the acceptability of formal patient charges for health‐care services in a basic package among different health‐care system stakeholders in six Central and Eastern European countries (Bulgaria, Hungary, Lithuania, Poland, Romania and Ukraine).

Methods

Qualitative data were collected in 2009 via focus group discussions and in‐depth interviews with health‐care consumers, providers, policy makers and insurers. The same participants were asked to fill in a self‐administrative questionnaire. Qualitative and quantitative data are analysed separately to outline similarities and differences in the opinions between the stakeholder groups and across countries.

Results

There is a rather weak consensus on patient charges in the countries. Health policy makers and insurers strongly advocate patient charges. Health‐care providers overall support charges but their financial profits from the system strongly affects their approval. Consumers are against paying for services, mostly due to poor quality and access to health‐care services and inability to pay.

Conclusions

To build consensus on patient charges, the payment policy should be responsive to consumers' needs with regard to quality and equity. Transparency and accountability in the health‐care system should be improved to enhance public trust and acceptance of patient payments.
Merkel cell carcinoma with divergent differentiation: histopathological and immunohistochemical study of 15 cases with PCR analysis for Merkel cell polyomavirus
Authors: Martin Blanca , Poblet Enrique , Rios Juan Jose , Kazakov Dmitry , Kutzner Heinz , Brenn Thomas , Calonje Eduardo
Published: December 2012

Aims

To report on 15 cases of Merkel cell carcinoma (MCC) with divergent differentiation, to characterize its clinicopathological spectrum and its relationship with Merkel cell polyomavirus (MCV).

Methods and results

Fifteen patients with a mean age of 81 years were included. Follow‐up was available for 13 cases (range 12 days to 6 years; median 6 months). Recurrence, metastasis and mortality rates were 15.4%, 53.8% and 61.5%, respectively. All tumours showed the typical histological and immunohistochemical features of MCC, with at least one additional divergent component. Eight cases had a single aberrant component (squamous in six cases, follicular in one case, and porocarcinoma in one case), six cases had two aberrant components (squamous and sarcomatous in three cases, glandular and squamous in two cases, and sarcomatous and neuroblastic in one case), and one case had three aberrant components (glandular, squamous, and sarcomatous). All cases had dysplastic changes in the overlying epithelium, and four of 15 showed epidermotropism. PCR analysis for Merkel cell polyomavirus (MCV) gave negative results in all 12 cases tested.

Conclusions

Merkel cell carcinoma with divergent differentiation is a highly aggressive tumour that might be difficult to recognize, owing to its wide histological variability. Negativity for MCV suggests that the virus is not implicated in the development of this subtype of MCC.
The effects of natural compounds‐containing mouthrinses on patients with fixed orthodontic appliance treatment: clinical and microbiological outcomes
Authors: Chen Yong , Wong Ricky W. K. , Seneviratne Chaminda Jayampath , Hagg Urban , McGrath Colman , Samaranayake Lakshman P.
Published: December 2012

Aim

To investigate the effects of two natural compounds‐containing mouthrinses (NCCMs) (a fructus mume (FM) extract–containing mouthrinse and an essential oil (EO)‐containing mouthrinse) on gingival health and microbial profiles in young orthodontic patients.

Design

This 6‐month randomized, single‐blinded, parallel‐controlled clinical trial consists of 90 patients with fixed appliance treatment. The subjects were allocated to (1) negative control group: oral hygiene instruction (OHI) alone; (2) test group 1: OHI plus EO mouthrinse; and (3) test group 2: OHI plus FM mouthrinse. Clinical examinations included plaque index (PI), bleeding index (BI) and modified gingival index (MGI). Salivary microbial quantifications included total aerobic and anaerobic bacteria, Streptococci and Lactobacilli counts. Clinical and microbiological examinations were conducted at baseline, 3rd and 6th months (T1, T2, and T3).

Results

BI was significantly reduced in both the FM mouthrinse and EO mouthrinse groups compared with the negative control group at T3 (P < 0.05). There were no significant intergroup differences in salivary bacteria counts in all groups (P > 0.05).

Conclusion

Both NCCMs effectively reduced gingival bleeding without causing significant alterations of microbial profile in young orthodontic patients.
Overview of the conference
Authors: Roberts Noel , Chand Meera
Published: December 2012

Please cite this paper as: Roberts et al. (2012) Overview of the conference. Influenza and Other Respiratory Viruses 7(Suppl. 1), 2–6.
Modeling the global transmission of antiviral‐resistant influenza viruses
Authors: Chao Dennis L.
Published: December 2012

Please cite this paper as: Chao. (2012) Modelling the global transmission of antiviral‐resistant influenza viruses. Influenza and Other Respiratory Viruses 7(Suppl. 1), 58–62.

Background  The mutations that confer resistance to antiviral agents are thought to be detrimental, or at best neutral, to influenza virus fitness. The fact that resistant influenza strains can circulate and sometimes replace sensitive strains is of great public health concern.

Objectives  We used mathematical modeling to test various hypotheses about the transmission of antiviral‐resistant influenza viruses by comparing the model’s output with the observed rise in antiviral resistance of seasonal A(H1N1) influenza viruses between 2006 and 2009.

Methods  We developed a mathematical model of the transmission of influenza among 321 cities around the globe. In the model, influenza strains resistant to antiviral agents competed with sensitive strains.

Results and Conclusions  We found that a resistant strain of influenza could not displace the sensitive strain as rapidly as has been observed unless it was more transmissible than the sensitive strain in the general population. We believe that an antiviral‐resistant strain displaced the antiviral‐sensitive seasonal A(H1N1) virus by hitchhiking on an escape mutation. Because of the complex global patterns of influenza circulation, tracking the emergence and spread of antiviral resistance must be a coordinated global effort.
Consequences of resistance: in vitro fitness, in vivo infectivity, and transmissibility of oseltamivir‐resistant influenza A viruses
Authors: Govorkova Elena A.
Published: December 2012

Please cite this paper as: Govorkova EA. (2012) Consequences of resistance: in vitro fitness, in vivo infectivity, and transmissibility of oseltamivir‐resistant influenza A viruses. Influenza and Other Respiratory Viruses 7(Suppl. 1), 50–57.

The development of drug resistance is a major drawback to any antiviral therapy, and the specific anti‐influenza drugs, the neuraminidase (NA) inhibitors (NAIs), are not excluded from this rule. The impact of drug resistance depends on the degree of reduction in fitness of the particular drug‐resistant virus. If the resistance mutations lead to only a modest biological fitness cost and the virus remains highly transmissible, the effectiveness of antiviral use is likely to be reduced. This review focuses on the fitness of oseltamivir‐resistant seasonal H1N1 and H3N2, 2009 pandemic H1N1 (H1N1pdm09), and highly pathogenic H5N1 influenza A viruses carrying clinically derived NAI resistance‐associated NA mutations.
Newer influenza antivirals, biotherapeutics and combinations
Authors: Hayden Frederick G.
Published: December 2012

Please cite this paper as: Hayden FG. (2012) Newer Influenza Antivirals, Biotherapeutics and Combinations. Influenza and Other Respiratory Viruses 7(Suppl. 1), 63–75.

This summary provides an overview of investigational antiviral agents for influenza and of future directions for development of influenza therapeutics. While progress in developing clinically useful antiviral agents for influenza has been generally slow, especially with respect to seriously ill and high‐risk patients, important clinical studies of intravenous neuraminidase inhibitors, antibodies and drug combinations are currently in progress. The current decade offers the promise of developing small molecular weight inhibitors with novel mechanisms of action, including host‐directed therapies, new biotherapeutics and drug combinations, that should provide more effective antiviral therapies and help mitigate the problem of antiviral resistance. Immunomodulatory interventions also offer promise but need to be based on better understanding of influenza pathogenesis, particularly in seriously ill patients. The development of combination interventions, immunomodulators and host‐directed therapies presents unique clinical trial design and regulatory hurdles that remain to be addressed.
Clinical use of approved influenza antivirals: therapy and prophylaxis
Authors: Ison Michael G.
Published: December 2012

Please cite this paper as: Ison. (2012) Clinical use of approved influenza antivirals: therapy and prophylaxis. Influenza and Other Respiratory Viruses 7(Suppl. 1), 7–13.

Currently, there are two commonly used classes of antiviral agents approved for the prevention of and treatment for influenza: the M2 Inhibitors (amantadine and rimantadine) and the neuraminidase inhibitors (oseltamivir, laninamivir, peramivir and zanamivir). These agents have been proven to be safe and effective alone or in combination for the treatment of uncomplicated influenza in otherwise healthy individuals. Although there are few prospective, randomized studies of these antivirals for the treatment of pregnant women, hospitalized patients, and immunocompromised patients infected with seasonal, pandemic, or avian H5N1 influenza, these agents are widely used for these indications. This article reviews the pharmacokinetics and clinical data available relative to the use of commercially available antiviral agents for the prevention of and treatment for influenza.