bluuebunny/crossref_metadata_2025 huggingface dataset:
Questionnaire Survey and Serum Phosphorus Levels in Maintenance Hemodialysis Patients Switching Lanthanum Carbonate Formulation From Chewable Tablets to Granules
Authors: Mukai Itsumi , Yoshizawa Taku , Kumagai Junko , Takahashi Naoko , Tsuchiya Shinichiro
Published: June 2014

We conducted a questionnaire survey of 79 maintenance hemodialysis patients switching lanthanum carbonate (LC) formulation from chewable tablets to granules, to investigate the compliance and patient preferences of these two formulations. For the number of times chewed when taking chewable tablets, the ratio of patients who responded 10 times or more was 54.4%, who responded four to nine times was 24.1% and who responded three times or less was 8.9%. Thirty‐seven patients (46.8%) responded “Granules are easier to take”, 22 patients (27.8%) responded “Chewable tablets are easier to take”, and 20 patients (25.3%) responded “No difference between formulations.” Changes in serum phosphorus (P) levels were also measured for 4 weeks after switching formulation, but no significant differences were observed before and after switching. We think that these questionnaire survey results show the compliance status and the patient needs for LC in the clinical practices.
Optimization of the Acceptance of Prebiotic Beverage Made from Cashew Nut Kernels and Passion Fruit Juice
Authors: Rebouças Marina Cabral , Rodrigues Maria do Carmo Passos , Afonso Marcos Rodrigues Amorim
Published: June 2014

The aim of this research was to develop a prebiotic beverage from a hydrosoluble extract of broken cashew nut kernels and passion fruit juice using response surface methodology in order to optimize acceptance of its sensory attributes. A 22 central composite rotatable design was used, which produced 9 formulations, which were then evaluated using different concentrations of hydrosoluble cashew nut kernel, passion fruit juice, oligofructose, and 3% sugar. The use of response surface methodology to interpret the sensory data made it possible to obtain a formulation with satisfactory acceptance which met the criteria of bifidogenic action and use of hydrosoluble cashew nut kernels by using 14% oligofructose and 33% passion fruit juice.
Impact of Almond Form and Moisture Content on Texture Attributes and Acceptability
Authors: Vickers Zata , Peck Amanda , Labuza Theodore , Huang Guangwei
Published: June 2014

The objectives of this study were to measure sensory texture attributes of 5 types of almonds (blanched slivered, natural sliced, whole blanched, whole dry roasted, and natural whole) conditioned at 4 different moisture levels, to measure liking of a subset of these products, and to compare the sensory texture measurements with consumer liking ratings. Thirteen panelists trained to evaluate almond texture rated the texture attributes of the 20 almond samples. A panel of 113 almond consumers rated their liking of a subset of 8 of these almonds. Compared with the whole almonds, sliced and slivered almonds had less hardness, less crunchiness, less cohesiveness, less tooth packing, and required fewer chews and swallows to consume. Compared with slivered almonds, sliced almonds were more powdery, had more surface roughness, more loose particles, and were crisper. Compared with slivered almonds, sliced almonds were less hard, broke into fewer pieces, had less moistness and cohesiveness of mass, less fatty film, and required fewer chews and fewer swallows to consume. Dry roasted almonds were generally harder, more crisp, more crunchy, and produced more loose particles than natural almonds, which were, in turn, more hard, crisp, and crunchy than blanched almonds. As moisture content increased, moistness of mass and cohesiveness of mass increased. Crispness, number of pieces, hardness, crunchiness, persistence of crunch, and particulate mass decreased with increasing moisture content. Consumer texture liking ratings were highly positively correlated with the attributes crispness, crunchiness, and persistence of crunch.
Shared signatures of social stress and aging in peripheral blood mononuclear cell gene expression profiles
Authors: Snyder‐Mackler Noah , Somel Mehmet , Tung Jenny
Published: June 2014

Chronic social stress is a predictor of both aging‐related disease and mortality risk. Hence, chronic stress has been hypothesized to directly exacerbate the process of physiological aging. Here, we evaluated this hypothesis at the level of gene regulation. We compared two data sets of genome‐wide gene expression levels in peripheral blood mononuclear cells (PBMCs): one that captured aging effects and another that focused on chronic social stress. Overall, we found that the direction, although not necessarily the magnitude, of significant gene expression changes tends to be shared between the two data sets. This overlap was observable at three levels: (i) individual genes; (ii) general functional categories of genes; and (iii) molecular pathways implicated in aging. However, we also found evidence that heterogeneity in PBMC composition limits the power to detect more extensive similarities, suggesting that our findings reflect an underestimate of the degree to which age and social stress influence gene regulation in parallel. Cell type‐specific data on gene regulation will be important to overcome this limitation in the future studies.
“Wired,” Yet Intoxicated: Modeling Binge Caffeine and Alcohol Co‐Consumption in the Mouse
Authors: Fritz Brandon M. , Companion Michel , Boehm Stephen L.
Published: June 2014

Background

The combination of highly caffeinated “energy drinks” with alcohol (ethanol [EtOH]) has become popular among young adults and intoxication via such beverages has been associated with an elevated risk for harmful behaviors. However, there are discrepancies in the human literature regarding the effect of caffeine on alcohol intoxication, perhaps due to confounding factors such as personality type, expectancy, and history of exposure. Animal models of co‐exposure are resistant to such issues; however, the consequences of voluntary co‐consumption have been largely ignored in the animal literature. The primary goal of this work was to characterize a mouse model of binge caffeine and EtOH co‐consumption employing the limited access “Drinking‐in‐the‐Dark” (DID) paradigm.

Methods

Caffeine was added to a 20% alcohol solution via DID. Alcohol/caffeine intake, locomotor behavior, ataxia, anxiety‐like behavior, and cognitive function were evaluated as a consequence of co‐consumption in adult male C57BL/6J mice.

Results

Caffeine did not substantially alter binge alcohol intake or resultant blood EtOH concentrations (BECs), nor did it alter alcohol's anxiolytic effects on the elevated plus maze or cognitive‐interfering effects in a novel object‐recognition task. However, no evidence of alcohol‐induced sedation was observed in co‐consumption groups that instead demonstrated a highly stimulated state similar to that of caffeine alone. The addition of caffeine was also found to mitigate alcohol‐induced ataxia.

Conclusions

Taken together, our mouse model indicates that binge co‐consumption of caffeine and alcohol produces a stimulated, less ataxic and anxious, as well as cognitively altered state; a state that could be of great public health concern. These results appear to resemble the colloquially identified “wide awake drunk” state that individuals seek via consumption of such beverages. This self‐administration model therefore offers the capacity for translationally valid explorations of the neurobiological consequences of binge co‐consumption to assess the public health risk of this drug combination.
Quality of life in major depressive disorder before/after multiple steps of treatment and one‐year follow‐up
Authors: IsHak W. W. , Mirocha J. , James D. , Tobia G. , Vilhauer J. , Fakhry H. , Pi S. , Hanson E. , Nashawati R. , Peselow E. D. , Cohen R. M.
Published: June 2014

Objective

This study examines the impact of major depressive disorder (MDD) and its treatment on quality of life (QOL).

Method

From the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, we analyzed complete data of 2280 adult MDD out‐patients at entry/exit of each level of antidepressant treatments and after 12 months of entry to follow‐up. QOL was measured using the QOL Enjoyment and Satisfaction Questionnaire (Q‐LES‐Q). The proportions of patients scoring ‘within‐normal’ QOL (within 10% of Q‐LES‐Q community norms) and those with ‘severely impaired’ QOL (>2 SD below Q‐LES‐Q community norms) were analyzed.

Results

Before treatment, no more than 3% of MDD patients experienced ‘within‐normal’ QOL. Following treatment, statistically significant improvements were detected; however, the proportion of patients achieving ‘within‐normal’ QOL did not exceed 30%, with >50% of patients experiencing ‘severely impaired’ QOL. Although remitted patients had greater improvements compared with non‐remitters, 32–60% continued to experience reduced QOL. 12‐month follow‐up data revealed that the proportion of patients experiencing ‘within‐normal’ QOL show a statistically significant decrease in non‐remitters.

Conclusion

Symptom‐focused treatments of MDD may leave a misleading impression that patients have recovered when, in fact, they may be experiencing ongoing QOL deficits. These findings point to the need for investigating specific interventions to ameliorate QOL in MDD.
Risk factors of cycle acceleration in acutely admitted patients with bipolar disorder
Authors: Finseth P. I. , Morken G. , Malt U. F. , Andreassen O. A. , Vaaler A. E.
Published: June 2014

Objective

To identify risk factors associated with cycle acceleration (CA), that is, progressive decrease in duration of syndrome‐free intervals between affective episodes, in acutely admitted patients with bipolar disorder (BD).

Method

All patients (n = 210) with BD I (67%) and BD II (33%) (DSM‐IV) acutely admitted to a hospital serving a catchment area were compared in retrospect with regard to a positive or negative history of CA. Putative risk factors of CA with a P‐value <0.05 in uni‐variate tests were secondly entered into a logistic regression model.

Results

The logistic regression model was statistically significant (P < 0.0001) and explained between 45.3% and 60.5% of the variance of CA status. 83.7% of the cases were correctly classified with a sensitivity of 87.2% and a specificity of 80.4%. Unique significant risk factors of CA were increasing severity of affective episodes (odds ratio (OR) = 28.8), BD II (OR = 3.3), hypomanic/manic episode induced by an antidepressant and/or alcohol (OR = 3.3), and female gender (OR = 3.1).

Conclusion

The clinical factors associated with CA may help targeting patients with BD with a course aggravation, and are in line with previously reported neuropathological processes of illness progression.
Standardized testing with chlorhexidine in perioperative allergy – a large single‐centre evaluation
Authors: Opstrup M. S. , Malling H.‐J. , Krøigaard M. , Mosbech H. , Skov P. S. , Poulsen L. K. , Garvey L. H.
Published: June 2014

Background

Perioperative allergic reactions to chlorhexidine are often severe and easily overlooked. Although rare, the prevalence remains unknown. Correct diagnosis is crucial, but no validated provocation model exists, and other diagnostic tests have never been evaluated. The aims were to estimate (i) the prevalence of chlorhexidine allergy in perioperative allergy and (ii) the specificity and sensitivity for diagnostic tests for chlorhexidine allergy.

Methods

We included all patients investigated for suspected perioperative allergic reactions in the Danish Anaesthesia Allergy Centre during 2004–2012. The following tests were performed: specificIgE(Immunocap®;PhadiaAB,Sweden), histamine release test (HR) (RefLabApS,Denmark), skin prick test (SPT) and intradermal test (IDT). Positivity criteria were as follows: specificIgE >0.35 kUA/l;HRclass 1–12;SPTmean wheal diameter ≥3 mm;IDTmean wheal diameter ≥ twice the diameter of negative control. Chlorhexidine allergy waspost hocdefined as a relevant clinical reaction to chlorhexidine combined with two or more positive tests. Based on this definition, sensitivity and specificity were estimated for each test.

Results

In total, 22 of 228 patients (9.6%) met the definition of allergy to chlorhexidine. Estimated sensitivity and specificity were as follows: specificIgE(sensitivity 100% and specificity 97%),HR(sensitivity 55% and specificity 99%),SPT(sensitivity 95% and specificity 97%) andIDT(sensitivity 68% and specificity 100%).

Conclusions

In patients investigated for suspected perioperative allergic reactions, 9.6% were diagnosed with allergy to chlorhexidine. Using our definition of chlorhexidine allergy, the highest combined estimated sensitivity and specificity was found for specific IgE andSPT.
Number, causes and destinations of horses leaving theAustralianThoroughbred andStandardbred racing industries
Authors: Thomson PC , Hayek AR , Jones B , Evans DL , McGreevy PD
Published: June 2014

Objective

Significant proportions of horses leave theAustralianThoroughbred andStandardbred racing industries, which has ramifications for both the economic sustainability and the public perception of racing. The aim of this study was to quantify potential horse wastage, describe the destinations of exiting horses and identify risk factors for horses going to these destinations.

Methods

Questionnaires were sent to 1258 selected Thoroughbred and 981 Standardbred trainers, with response rates of 30% and 32%, respectively. The survey investigated the role of various risk factors for wastage, including horse age, sex and number of years in training. The destination of departing horses was also examined in relation to these risk factors.

Results

Total horse exit rates for the 2002–03 official race year were 39.7% and 38.7% for the Thoroughbred and Standardbred racing industries, respectively. Reasons for leaving included ‘poor performance/slow’ (36.5% Thoroughbreds, 35.2% Standardbreds), ‘illness/injury’ (31.0%, 27.1%), ‘to breed’ (9.4%, 10.1%), ‘unsuitable temperament/behaviour’ (6.4%, 6.4%) and ‘other’ (16.8%, 21.2%). Statistically significant (P < 0.001) risk factors influencing the destinations of both Thoroughbred and Standardbred racing horses included whether the trainer owned the horses, sex, age and reasons for leaving. In addition, some factors were specific to one breed or the other.

Conclusions

Improved behaviour training and early identification of the causes of poor performance could assist in reducing wastage.
Gross morphology and topographical relationships of the hyobranchial apparatus and laryngeal cartilages in the ostrich (Struthio camelus)
Authors: Soley John T. , Tivane Catarina , Crole Martina R.
Published: June 2014

The ostrich hyobranchial apparatus consists of the centrally positioned paraglossalia and basiurohyale and paired caudo‐lateral elements (horns), each consisting of the ceratobranchiale and epibranchiale. The paraglossalia lie within the tongue parenchyma and consist of paired, flat, caudo‐laterally directed cartilages joined rostrally. The basiurohyale forms a single dorso‐ventrally flattened unit composed of an octagonal‐shaped body from which extend rostral (the rostral process) and caudal (the urohyale) projections. The laryngeal skeleton consists of cricoid, procricoid and paired arytenoid cartilages. The large ring‐shaped cricoid cartilage displays a body and paired wings which articulate with each other and with the procricoid. The blunt, ossified, rostral projection of the cricoid and the scalloped nature of the arytenoid cartilages are unique to the ostrich. The procricoid is a single structure which links the paired arytenoids and wings of the cricoid. The hyobranchial apparatus is firmly attached to the tongue parenchyma and to the larynx and proximal trachea. In contrast to previous reports in this species, the horns of the hyobranchial apparatus are not related to the skull. Ossification of the body of the basihyale, the ceratobranchials and the rostral process and body of the cricoid cartilage of the larynx lends stability to these structures.
Children's utilization of emotion expectancies in moral decision‐making
Authors: Hertz Steven G. , Krettenauer Tobias
Published: June 2014

This study investigated the relevance of emotion expectancies for children's moral decision‐making. The sample included 131 participants from three different grade levels (M = 8.39 years, SD = 2.45, range 4.58–12.42). Participants were presented a set of scenarios that described various emotional outcomes of (im)moral actions and asked to decide what they would do if they were in the protagonists' shoes. Overall, it was found that the anticipation of moral emotions predicted an increased likelihood of moral choices in antisocial and prosocial contexts. In younger children, anticipated moral emotions predicted moral choice for prosocial actions, but not for antisocial actions. Older children showed evidence for the utilization of anticipated emotions in both prosocial and antisocial behaviours. Moreover, for older children, the decision to act prosocially was less likely in the presence of non‐moral emotions. Findings suggest that the impact of emotion expectancies on children's moral decision‐making increases with age. Contrary to happy victimizer research, the study does not support the notion that young children use moral emotion expectancies for moral decision‐making in the context of antisocial actions.
Characterization of ibrutinib‐sensitive and ‐resistant mantle lymphoma cells
Authors: Ma Jiao , Lu Pin , Guo Ailin , Cheng Shuhua , Zong Hongliang , Martin Peter , Coleman Morton , Wang Y. Lynn
Published: June 2014

Ibrutinib inhibits Bruton tyrosine kinase (BTK), a key component of early B‐cell receptor (BCR) signalling pathways. A multicentre phase 2 trial of ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL) demonstrated a remarkable response rate. However, approximately one‐third of patients have primary resistance to the drug while other patients appear to lose response and develop secondary resistance. Understanding the molecular mechanisms underlying ibrutinib sensitivity is of paramount importance. In this study, we investigated cell lines and primary MCL cells that display differential sensitivity to ibrutinib. We found that the primary cells display a higher BTK activity than normal B cells and MCL cells show differential sensitivity to BTK inhibition. Genetic knockdown of BTK inhibits the growth, survival and proliferation of ibrutinib‐sensitive but not resistant MCL cell lines, suggesting that ibrutinib acts through BTK to produce its anti‐tumour activities. Interestingly, inhibition of ERK1/2 and AKT, but not BTK phosphorylation per se, correlates well with cellular response to BTK inhibition in cell lines as well as in primary tumours. Our study suggests that, to prevent primary resistance or to overcome secondary resistance to BTK inhibition, a combinatory strategy that targets multiple components or multiple pathways may represent the most effective approach.
Laparoendoscopic single‐site (LESS) robot‐assisted partial nephrectomy (RAPN) reduces postoperative wound pain without a rise in complication rates
Authors: Shin Tae Young , Lim Sey Kiat , Komninos Christos , Kim Dong Wook , Han Woong Kyu , Hong Sung Jun , Jung Byung Ha , Rha Koon Ho
Published: June 2014

Objective

To compare long‐term functional outcomes and pain scale scores of patients who underwent laparoendoscopic single‐site (LESS)‐ robot‐assisted partial nephrectomy (RAPN) to those who underwent conventional RAPN (C‐RAPN), as LESS surgery is increasingly being adopted by urologists worldwide to reduce morbidities and scarring associated with surgical interventions.

Patients and Methods

In all, 167 consecutive patients who had RAPN were identified from our Institutional Review Board‐approved computerised database between October 2006 to July 2012. Patients were stratified into two groups: 80 patients who underwent C‐RAPN and 79 who underwent LESS‐RAPN.

Results

The LESS‐RAPN group had a longer warm ischaemia time [WIT, mean (sd) 26.5 (10.5) vs 19.8 (13.1) min; P = 0.001] and total operation time [TOT, mean (sd) 210.3 (83.4) vs 183.1 (76.1) min; P = 0.033] when compared with the C‐RAPN group. While, the LESS‐RAPN group and C‐RAPN group were not significantly different for the number of patients with negative surgical margins [77 (96.2%) vs 73 (91.4%); P = 0.194), absolute change in postoperative renal function [mean (sd) −6.5 (16.7)% vs −7.6 (16.7)%; P = 0.738) and postoperative complications rate [12 (15.0%) vs 10 (12.6%); P = 0.279). Furthermore, the LESS‐RAPN group had lower visual analogue pain scale (VAPS) scores at discharge [mean (sd) 2.1 (1.3) vs 1.7 (1.0); P = 0.048].

Conclusions

Despite a significantly longer WIT and TOT, the functional outcomes of LESS‐RAPN were comparable to those of C‐RAPN for tumours of similar mean sizes and complexities, without any detriments in oncological and complications outcomes. On discharge, patients who underwent LESS‐RAPN also reported lower pain levels as one of the advantages of minimally invasive surgery. With the development of instrumentation specifically designed for single‐site surgery, LESS could be more easily conducted in patients who are interested in improved quality of life outcomes.
Long‐term functional outcomes after artificial urinary sphincter implantation in men with stress urinary incontinence
Authors: Léon Priscilla , Chartier‐Kastler Emmanuel , Rouprêt Morgan , Ambrogi Vanina , Mozer Pierre , Phé Véronique
Published: June 2014

Objective

To evaluate long‐term functional outcomes of artificial urinary sphincters (AUSs) and to determine how many men required explantation because of stress urinary incontinence (SUI) caused by sphincter deficiency after prostate surgery.

Patients and Methods

Men who had undergone placement of an AUS (American Medical Systems AMS 800®) between 1984 and 1992 to relieve SUI caused by sphincter deficiency after prostate surgery were included. Continence, defined as no need for pads, was assessed at the end of the follow‐up. Kaplan–Meier survival curves estimated the survival rate of the device without needing explantation or revision.

Results

In all, 57 consecutive patients were included with a median (interquartile range, IQR) age of 69 (64–72) years. The median (IQR) duration of follow‐up was 15 (8.25–19.75) years. At the end of follow‐up, 25 patients (43.8%) still had their primary AUS. The AUS was explanted in nine men because of erosion (seven) and infection (two). Survival rates, without AUS explantation, were 87%, 87%, 80%, and 80% at 5, 10, 15, and 20 years, respectively. Survival rates, without AUS revision, were 59%, 28%, 15%, and 5% at 5, 10, 15, and 20 years, respectively. At the end of the follow‐up, in intention‐to‐treat analysis, 77.2% of patients were continent.

Conclusion

In the long term (>10 years) the AMS 800 can offer a high rate of continence to men with SUI caused by sphincter deficiency, with a tolerable rate of explantation and revision.
Incidence of needle‐tract seeding following prostate biopsy for suspected cancer: a review of the literature
Authors: Volanis Dimitrios , Neal David E. , Warren Anne Y. , Gnanapragasam Vincent J.
Published: June 2014

With the widespread clinical use of prostate‐specific antigen (PSA), biopsy of the prostate has become one of the most commonly performed urological procedures. In general it is well tolerated, although there is some morbidity and risk of infection. In recent years, there have been increasing concerns that prostate biopsy may lead to tumour seeding along the needle tract. The aim of the present paper was to review the evidence on the prevalence of tumour seeding after prostate biopsy and to define the risk of this event in the context of current clinical practice. A PubMed literature search was conducted in January 2014 according to the Preferred Reporting Items for Systematic Reviews and Meta‐analysis (PRISMA) statement. Literature was examined with emphasis on the incidence of seeding, clinical presentation and on risk factors including type of needle used, transrectal vs transperineal approach, as well as tumour grade and stage. In all, 26 publications were identified reporting needle‐tract seeding after prostate biopsy. In all, 42 patients with needle‐tract seeding were identified. In most cases, seeding was reported after transperineal biopsy of the prostate, while nine cases occurred after transrectal biopsy. Based on the reviewed series the incidence of seeding appears to be <1%. The increase in the number of biopsies and cores taken at each biopsy over the years has not resulted in an increase in the reported cases of seeding. In conclusion, seeding along the needle track is a rare complication after prostate biopsy. Its actual incidence is presently difficult to quantify. It is reasonable to advise appropriate counselling and take measures to reduce this event where possible; however, we do not advocate avoidance of biopsies as the benefits of appropriate cancer diagnosis and management outweigh any potential risks from seeding.
The impact of robotic surgery on the surgical management of prostate cancer in the USA
Authors: Chang Steven L. , Kibel Adam S. , Brooks James D. , Chung Benjamin I.
Published: June 2014

Objective

To describe the surgeon characteristics associated with robot‐assisted radical prostatectomy (RARP) adoption and determine the possible impact of this adoption on practice patterns and cost.

Patients and Methods

A retrospective cohort study with a weighted sample size of 489 369 men who underwent non‐RARP (i.e., open or laparoscopic RP) or RARP in the USA from 2003 to 2010 was performed. We evaluated predictors for RARP adoption, defined as performing >50% of annual RP using the robotic approach. Additionally, we identified the resulting changes in prostate cancer surgery practice patterns and expenditures.

Results

From 2003 to 2010, RARP adoption increased from 0.7% to 42% of surgeons performing RP. High‐volume surgeons, defined as performing >24 RPs annually, had statically significantly higher odds of adopting RARP throughout the study period. From 2005 to 2007, adoption was more common among surgeons at teaching (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.7–3.4), intermediate‐ (200–399 beds; OR 5.96, 95% CI 1.3–26.5) and large‐sized hospitals (≥400 beds; OR 6.1, 95% CI 1.4–25.8); after 2007, adoption was more common among surgeons at urban hospitals (OR 3.3, 95% CI 1.7–6.4). RARP adoption was generally associated with increased RP volume, greatest for high‐volume surgeons and least for low‐volume surgeons (<5 RPs annually). The annual number of surgeons performing RP decreased from about 10 000 to 8200, with the proportion of cases performed by high‐volume surgeons increasing from 10% to 45%. RARP was more costly, disproportionally contributing to the 40% increase in annual prostate cancer surgery expenditures. RARP costs generally decreased plateauing at slightly over $10 000, while non‐RARP costs increased to nearly $9000 by the end of the study.

Conclusion

There was widespread RARP adoption in the USA between 2003 and 2010, particularly among high‐volume surgeons. The diffusion of RARP was associated with a centralisation of care and an increased economic burden for prostate cancer surgery.
Drug effects on the CVS in conscious rats: separating cardiac output into heart rate and stroke volume using PKPD modelling
Authors: Snelder N , Ploeger B A , Luttringer O , Rigel D F , Fu F , Beil M , Stanski D R , Danhof M
Published: June 2014

Background and Purpose

Previously, a systems pharmacology model was developed characterizing drug effects on the interrelationship between mean arterial pressure (MAP), cardiac output (CO) and total peripheral resistance (TPR). The present investigation aims to (i) extend the previously developed model by parsing CO into heart rate (HR) and stroke volume (SV) and (ii) evaluate if the mechanism of action (MoA) of new compounds can be elucidated using only HR and MAP measurements.

Experimental Approach

Cardiovascular effects of eight drugs with diverse MoAs (amiloride, amlodipine, atropine, enalapril, fasudil, hydrochlorothiazide, prazosin and propranolol) were characterized in spontaneously hypertensive rats (SHR) and normotensive Wistar‐Kyoto (WKY) rats following single administrations of a range of doses. Rats were instrumented with ascending aortic flow probes and aortic catheters/radiotransmitters for continuous recording of MAP, HR and CO throughout the experiments. Data were analysed in conjunction with independent information on the time course of the drug concentration following a mechanism‐based pharmacokinetic‐pharmacodynamic modelling approach.

Key Results

The extended model, which quantified changes in TPR, HR and SV with negative feedback through MAP, adequately described the cardiovascular effects of the drugs while accounting for circadian variations and handling effects.

Conclusions and Implications

A systems pharmacology model characterizing the interrelationship between MAP, CO, HR, SV and TPR was obtained in hypertensive and normotensive rats. This extended model can quantify dynamic changes in the CVS and elucidate the MoA for novel compounds, with one site of action, using only HR and MAP measurements. Whether the model can be applied for compounds with a more complex MoA remains to be established.
Interleukin 10 gene promoter polymorphisms in women with early-onset pre-eclampsia
Authors: Sowmya S , Sri Manjari K , Ramaiah A , Sunitha T , Nallari P , Jyothy A , Venkateshwari A
Published: June 2014

Pre-eclampsia is one of the most serious disorders of human pregnancy and T helper type 1 (Th1)/Th2 imbalance plays a major role in its aetiology. The Th2 cytokine, interleukin (IL)-10, plays a significant role in the maintenance of pregnancy. The present study is aimed at understanding the role of IL-10 promoter polymorphisms (−1082 G/A; −592 A/C and −819 C/T) and their haplotypes in early-onset pre-eclampsia. A total of 120 patients and an equal number of women with normal pregnancy, from Government Maternity Hospital, Petlaburz, Hyderabad, India, were considered for the present study. A standard amplification refractory mutation system–polymerase chain reaction (ARMS–PCR) was carried out for genotyping followed by agarose gel electrophoresis. Appropriate statistical methods were applied to test for the significance of the results. It was found that the IL-10 −819 C allele (P = 0·003) and −592 A (P = 0·005) allele frequencies increased significantly in patients compared to controls. No significant difference was found with regard to −1082 promoter polymorphism. Haplotype analysis of the IL-10 single nucleotide polymorphisms (SNPs) revealed a significant association with ACC haplotype with a twofold increased risk in patients compared to controls. The frequencies of two common IL-10 haplotypes (GCC and ATA) did not show any significant difference. Further, the diplotype analysis revealed five genotypes: −1082A with −819C (P = 0·0016); −1082G with −819C (P = 0·0018); −819C with −592C (P = 0·001); −1082A with −592C (P = 0·032); and −1082G with −592C (P = 0·005) associated with the disease. These findings support the concept of contribution of IL-10 gene polymorphisms in the pathogenesis of early-onset pre-eclampsia.
Higher ferritin levels, but not serum iron or transferrin saturation, are associated with Type 2 diabetes mellitus in adult men and women free of genetic haemochromatosis
Authors: Yeap Bu B. , Divitini Mark L. , Gunton Jenny E. , Olynyk John K. , Beilby John P. , McQuillan Brendan , Hung Joseph , Knuiman Matthew W.
Published: June 2014

Context

Iron overload predisposes to diabetes and higher ferritin levels have been associated with diabetes. However, it is unclear whether ferritin reflects differences in iron‐related parameters between diabetic and nondiabetic persons. We examined associations of serum ferritin, iron and transferrin saturation with Type 2 diabetes in adults without genetic predisposition to iron overload.

Design, participants and measurements

Cross‐sectional analysis of community‐dwelling men and women aged 17–97 years from the Busselton Health Survey, Western Australia. Men and women carrying genotypes associated with haemochromatosis (C282Y/C282Y or C282Y/H63D) were excluded. Serum ferritin, iron and transferrin saturation were assayed.

Results

There were 1834 men (122 with diabetes, 6·6%) and 2351 women (141 with diabetes, 6%). In men, higher serum ferritin was associated with diabetes after adjusting for age, smoking, alcohol, cardiovascular history, body mass index (BMI), waist, blood pressure, lipids, C‐reactive protein (CRP), adiponectin, alanine transaminase (ALT) and gamma‐glutamyl transpeptidase (GGT) [odds ratio (OR): 1·29 per 1 unit increase log ferritin, 95% confidence interval (CI) = 1·01–1·65, P = 0·043]. In women, higher serum ferritin was associated with diabetes [fully adjusted OR: 1·31 per 1 unit increase log ferritin, 95% CI = 1·04–1·63, P = 0·020; 1·84 for tertile (T) 3 vs T1, 95% CI = 1·09–3·11]. Neither iron levels nor transferrin saturation were associated with diabetes risk in men or women. Higher ferritin was not associated with insulin resistance in nondiabetic adults.

Conclusions

In adults, higher ferritin levels are independently associated with prevalent diabetes while iron and transferrin saturation are not. Ferritin is a robust biomarker for diabetes risk, but further investigation is needed to clarify whether this relationship is mediated via iron metabolism.
EIF2AK4 genetic mutations cause a recessive form of rare and deadly lung disease, pulmonary veno‐occlusive disease
Authors: Aminkeng F.
Published: June 2014

EIF2AK4 mutations cause pulmonary veno‐occlusive disease, a recessive form of pulmonary hypertension.

Eyries et al. (2014)

Nature Genetics 46(1):65–69.
Moving Beyond Science to Protect a Mammalian Migration Corridor
Authors: BERGER JOEL , CAIN STEVEN L.
Published: June 2014

As the discipline of conservation biology evolves and practitioners grow increasingly concerned about how to put results into achievable conservation, it is still unclear the extent to which science drives conservation outcomes, especially across rural landscapes. We addressed this issue by examining the role of science in the protection of a biological corridor. Our focus is on a North American endemic mammal reliant on long distance migration as an adaptive strategy, the pronghorn (Antilocapra americana) of the southern Greater Yellowstone Ecosystem. The role of science in realizing policy change, while critical as a first step, was surprisingly small relative to the role of other human dimensions. In a case study, we strategically addressed a variety of conservation needs beyond science, first by building a partnership between government and private interests and then by enhancing interest in migratory phenomena across a landscape with divergent political ideologies and economic bases. By developing awareness and even people's pride in the concept of corridor conservation, we achieved local, state, and federal acceptance for protection of a 70 km long, 2 km wide pathway for the longest terrestrial migrant in the contiguous United States. Key steps included conducting and publishing research that defined the migration corridor; fostering a variety of media coverage at local, regional, and national levels; conducting public outreach through stakeholder workshops, meetings, and presentations; and meeting with and gaining the support of elected officials. All these contributed to the eventual policy change that created the first federally protected migration corridor in the United States, which in turn stimulated additional conservation actions. On the basis of our experience, we believe conservation scientists can and should step beyond traditional research roles to assist with on‐the‐ground conservation by engaging in aspects of conservation that involve local communities and public policy.

Ir Más Allá de la Ciencia para Proteger un Corredor Migratorio de Mamíferos
User Activities Outliers Detection; Integration of Statistical and Computational Intelligence Techniques
Authors: Mahmoud Sawsan , Lotfi Ahmad , Langensiepen Caroline
Published: June 2014

In this article, a hybrid technique for user activities outliers detection is introduced. The hybrid technique consists of a two‐stage integration of principal component analysis and fuzzy rule‐based systems. In the first stage, the Hamming distance is used to measure the differences between different activities. Principal component analysis is then applied to the distance measures to find two indices of Hotelling's T2 and squared prediction error. In the second stage of the process, the calculated indices are provided as inputs to the fuzzy rule‐based systems to model them heuristically. The model is used to identify the outliers and classify them. The proposed system is tested in real home environments, equipped with appropriate sensory devices, to identify outliers in the activities of daily living of the user. Three case studies are reported to demonstrate the effectiveness of the proposed system. The proposed system successfully identifies the outliers in activities distinguishing between the normal and abnormal behavioral patterns.
Cutaneous histoplasmosis in renal transplant recipients
Authors: Sun N. Z. , Augustine J. J. , Gerstenblith M. R.
Published: June 2014

Cutaneous histoplasmosis is a rare entity, although it can be seen in a substantial portion of renal transplant recipients with disseminated disease. The prognosis of disseminated disease is worse than isolated cutaneous involvement, and significant delays in diagnosis are reported. We reviewed reports of cutaneous histoplasmosis with and without dissemination in the setting of renal transplantation to examine incidence, timing of diagnosis, clinical features, and prognosis. Remarkable morphologic variability and the non‐specific appearance of skin findings suggest that tissue culture is required for definitive diagnosis. Cutaneous lesions represent an easily accessible source for early diagnosis.
Microorganisms of the toe web and their importance for erysipelas of the leg
Authors: Müller Dominik‐Patrick , Hoffmann Reinhard , Welzel Julia
Published: June 2014

Background

There has been a steady increase of the incidence of erysipelas in Germany in the recent past. Affected patients also often show defects in the cutaneous barrier caused by microorganisms. The aim of this non‐interventional case‐control study was to investigate a possible interrelationship between interdigital tinea pedis and bacterial toe web (interdigital space) infections and erysipelas of the leg, as well as a potential interaction among the microorganisms themselves.

Material and methods

The patient population contained 150 people equally distributed among three groups, one retrospective and one prospective erysipelas group (EG = rEG + pEG) plus one control group (KG).

Results

51 % of the patients with erysipelas and 32 % of the control group suffered from interdigital tinea pedis. There was a significant association between interdigital tinea pedis and the recurrence rate of erysipelas, but not with erysipelas itself. Staphylococcus aureus (EG: 30.34 %; KG: 3.23 %) and non‐pathogenic aerobic bacteria were significantly associated with erysipelas in each statistical analysis. Staphylococcus aureus showed a positive, the non‐pathogenic aerobic germs (EG: 28,09 %; KG: 80,65 %) a negative association.

Conclusions

This study demonstrates an association between the microorganisms of the toe web and erysipelas of the leg. Erysipelas itself is influenced to a great extent by the bacterial flora, while its recurrence relates more to interdigital tinea pedis.
Functional status at 18 months of age as a predictor of childhood disability after neonatal hypoxic‐ischemic encephalopathy
Authors: Natarajan Girija , Shankaran Seetha , Pappas Athina , Bann Carla , Tyson Jon E , McDonald Scott , Das Abhik , Hintz Susan , Vohr Betty , Higgins Rosemary ,   the Extended Hypothermia Subcommittee of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
Published: June 2014

Aim

In children with neonatal hypoxic‐ischemic encephalopathy (HIE), we examined the association between 18‐month functional status by parental report and disability at 6‐7 years.

Method

Prospective observational study involving participants in the NICHD randomized controlled trial of hypothermia for HIE. Parent questionnaires‐Functional Status‐II (FS‐II), Impact on Family (IOF) and Family Resource Scale (FRS) at 18 months were correlated with 6‐ to 7‐year developmental assessments. Disability at 6‐7 years was defined as IQ < 70, gross motor functional classification scale level III‐V, bilateral blindness, deafness, or epilepsy.

Results

Rates of severe HIE (32 vs. 15%), public insurance (73% vs. 47%) and IOF scales were higher and mean (SD) FS‐II independence (I) {54 (SD 35) vs. 98 (SD 8)} and general health (GH) {87 (SD 14) vs. 98 (SD 6)} scores were significantly lower in children with disability (n=37) at 6‐7 years, compared to those (n=74) without disability. FS‐II I scores were significantly associated with disability (OR 0.92; 95% CI 0.87‐0.97; p=0.003). On path analysis, severe HIE, greater IOF and public insurance were associated with poorer 18‐month FS‐II I scores, which, in turn, were associated with disability at 6 to 7 years.

Interpretation

Poor independent functioning by parental report at 18 months in children with HIE was associated with childhood disability.
Should thyroid‐stimulating hormone goals be reviewed in patients with Type 1 diabetes mellitus? Results from The Brazilian Type 1 Diabetes Study Group
Authors: Rodacki M. , Zajdenverg L. , Dantas J. R. , de Oliveira J. E. P. , Luiz R. R. , Cobas R. A. , Palma C. C. S. , Negrato C. A. , Gomes M. B.
Published: June 2014

Aims

To investigate if thyroid‐stimulating hormone (TSH) levels are associated with any differences in glycaemic control or diabetes‐related complications in individuals with Type 1 diabetes.

Methods

This observational, cross‐sectional and multicentre study included patients with Type 1 diabetes for ≥ 5 years, with a recent TSH measurement and without a known previous thyroid disease. Patients were divided into three groups according to TSH levels: 0.4–2.5 mU/l; 2.5–4.4 mU/l; and ≥ 4.5 mU/l.

Results

We included 1205 individuals with a mean ± sd age of 23.8 ± 11.3 years. Seven patients had TSH levels <0.4 mU/l and were excluded from the comparison between groups. HbA1c levels, systolic and diastolic blood pressure, LDL cholesterol and disease duration were similar in all groups (P = 0.893, P = 0.548, P = 0.461, P = 0.575 and P = 0.764, respectively). The rates of diabetic retinopathy and GFR < 60/mL/min/1.73 m2 differed between groups (P = 0.006 and P < 0.001, respectively) and were lower in those with lower TSH levels. Multivariate analysis confirmed these associations. The frequencies of retinopathy and GFR < 60 mL/min/1.73 m2 were higher not only in patients with TSH ≥ 4.5 mU/l (odds ratio 1.878 and 2.271, respectively) but also in those with TSH levels of 2.5–4.4 mU/l (odds ratio 1.493 and 2.286, respectively), when compared with patients with TSH levels of 0.4–2.5 mU/l.

Conclusions

TSH levels of 0.4–2.5 mU/l are associated with a lower risk of diabetic retinopathy and renal failure in individuals with Type 1 diabetes, independently of glycaemic control and duration of the disease.
Obesity index and the risk of diabetes among Chinese women with prior gestational diabetes
Authors: Wang L. , Liu H. , Zhang S. , Leng J. , Liu G. , Zhang C. , Li W. Q. , Li N. , Li W. , Li Y. , Sun S. , Yu Z. , Yang X. , Hu G.
Published: June 2014

Aims

There is some confusion regarding which anthropometric measurement of adiposity should be used to indicate diabetes, especially for Asians. The present study was to evaluate different indicators of adiposity (BMI, waist circumference and body fat) with Type 2 diabetes risk among women with prior gestational diabetes mellitus.

Methods

We performed a cross‐sectional survey in 1263 women with gestational diabetes at 1–5 years after delivery. Logistic regression models were used to estimate the association of BMI, waist circumference and body fat with Type 2 diabetes risk.

Results

BMI, waist circumference and body fat were all associated with an increased risk of Type 2 diabetes among women with prior gestational diabetes (all Ptrend < 0.001). After adjustment for waist circumference and body fat, the positive association of BMI with Type 2 diabetes risk became non‐significant and reversed. There was a significantly positive association of waist circumference with Type 2 diabetes risk after adjustment for BMI, and a significantly positive association of body fat with Type 2 diabetes risk after adjustment for both BMI and waist circumference. When the joint effects were examined, the significantly positive associations of waist circumference or body fat with Type 2 diabetes risk were consistent among women with different levels of BMI, and the positive association of BMI and Type 2 diabetes risk was significant among women with gestational diabetes with a waist circumference of ≥ 50% or body fat ≥ 50%.

Conclusions

BMI, waist circumference and body fat were all associated with an increased risk of Type 2 diabetes, and waist circumference and body fat were better indicators than BMI for Type 2 diabetes risk among Chinese women with prior gestational diabetes.
Ovipositional preferences and larval survival of annual bluegrass weevil, Listronotus maculicollis, on Poa annua and selected bentgrasses (Agrostis spp.)
Authors: Kostromytska Olga S. , Koppenhöfer Albrecht M.
Published: June 2014

The annual bluegrass weevil (ABW), Listronotus maculicollis Kirby (Coleoptera: Curculionidae), is a serious and expanding pest of short‐cut turfgrass on golf courses in eastern North America. Increasing problems with the development of insecticide resistance in this pest highlights the need for more sustainable management approaches. Plant resistance is one of the most promising alternative strategies. Bentgrasses are the dominant grass species on golf course fairways, tees, and putting greens in the areas affected by ABW. But Poa annua L. (Poaceae), a highly invasive weed, often constitutes a large percentage of turf stands in short‐mown golf courses and is thought to be particularly susceptible to ABW. We studied resistance to ABW in four cultivars of creeping bentgrass, Agrostis stolonifera L., and two cultivars each of colonial bentgrass, Agrostis capillaris L., and velvet bentgrass, Agrostis canina L. (Poaceae), in comparison with P. annua by addressing the three major components of resistance: antixenosis (adult ovipositional and feeding preferences), antibiosis (larval survival and growth), and grass tolerance (grass damage). Our findings suggest that antixenosis/non‐preference is at least partially involved in bentgrass resistance to ABW. Even though oviposition was observed in all tested grasses, females laid significantly fewer eggs in Agrostis spp. than in P. annua. Compared to P. annua, Agrostis spp. were also less suitable for larval development with lower numbers of ABW immatures recovered and larvae weighing less and being less advanced in development. Resistance levels to ABW larvae varied significantly among Agrostis spp. and cultivars. Agrostis canina was least preferred by females for oviposition and A. stolonifera was the least suitable for larval survival and development. Agrostis spp., especially A. stolonifera, were more tolerant to ABW feeding than P. annua. Our findings suggest that reduction in P. annua and replacement with Agrostis spp., especially A. stolonifera, wherever feasible should be integral to more sustainable approaches to ABW management.