bluuebunny/crossref_metadata_2025 huggingface dataset:
Considerations on the Aquaculture Development and on the Use of Veterinary Drugs: Special Issue for Fluoroquinolones—A Review
Authors: Quesada Silvia Pilco , Paschoal Jonas Augusto Rizzato , Reyes Felix Guillermo Reyes
Published: August 2013

Aquaculture has become an important source of fish available for human consumption. In order to achieve greater productivity, intensive fish cultivation systems are employed, which can cause greater susceptibility to diseases caused by viruses, bacteria, fungi, and parasites. Antimicrobial substances are compounds used in livestock production with the objectives of inhibiting the growth of microorganisms and treatment or prevention of diseases. It is well recognized that the issues of antimicrobial use in food animals are of global concern about its impact on food safety. This paper present an overview of the aquaculture production in the whole world, raising the particularities in Brazil, highlighting the importance of the use of veterinary drugs in this system of animal food production, and address the potential risks arising from their indiscriminate use and their impacts on aquaculture production as they affect human health and the environment. The manuscript also discusses the analytical methods commonly used in the determination of veterinary drug residues in fish, with special issue for fluroquinolones residues and with emphasis on employment of LC‐MS/MS analytical technique.
Identification of Sensory Attributes That Drive Consumer Liking of Commercial Orange Juice Products in Korea
Authors: Kim Mina K. , Lee Young‐Jin , Kwak Han Sub , Kang Myung‐woo
Published: August 2013

Orange juice is a well‐accepted fruit juice, and its consumption increases steadily. Many studies have been conducted to understand the sensory characteristics of orange juice throughout its varying processing steps. Sensory language and consumer likings of food can be influenced by culture. The objective of this study is to evaluate the sensory characteristics of commercially available orange juices in Korea and identify drivers of liking for orange juices in Korea. A quantitative descriptive analysis was conducted using a trained panel (n = 10) to evaluate 7 orange juice samples in triplicates, followed by consumer acceptance tests (n = 103). Univariate and multivariate statistical analyses were conducted for data analysis. The sensory characteristics of commercially available orange juice were documented and grouped: group 1 samples were characterized by high in natural citrus flavors such as orange peel, orange flesh, citrus fruit, and grape fruit, whereas group 2 samples were characterized by processed orange‐like flavors such as over‐ripe, cooked‐orange, and yogurt. Regardless of orange flavor types, a high intensity of orange flavor in orange juice was identified as a driver of liking for orange juices in Korea. Three distinct clusters were segmented by varying sensory attributes that were evaluated by likes and dislikes. Overall, many similarities were noticed between Korean market segment and global orange juice market. By knowing the drivers of liking and understanding the distinct consumer clusters present in the Korean orange juice market, the orange juice industry could improve the strategic marketing of its products in Korea.
Influence of ketanserin on the effects of methylenedioxymethamphetamine on body temperature in the mouse
Authors: Docherty J. R. , Bexis S.
Published: August 2013

We have investigated the ability of the 5HT2‐receptor antagonist ketanserin to affect the hyperthermia produced by methylenedioxymethamphetamine (MDMA) in conscious mice and examined whether α1‐adrenoceptor antagonist actions are involved.

Mice were implanted with intra‐abdominal temperature probes under anaesthesia and allowed 2 weeks recovery. MDMA (20 mg kg−1) was administered subcutaneously 30 min after vehicle or test antagonist and effects on body temperature monitored by telemetry.

Following vehicle, MDMA produced a slowly developing hyperthermia, reaching a maximum increase of 1.24 °C at 150 min postinjection. Ketanserin (0.5 mg kg−1) revealed a significant and marked early hypothermia to MDMA, an effect that is mimicked by the α1‐adrenoceptor antagonist prazosin (0.1 mg kg−1).

Functional studies revealed antagonist actions of ketanserin at α1‐adrenoceptors in rat aorta and rat vas deferens in vitro indicative of α1‐adrenoceptor antagonist actions at the concentration used in vivo.

In conclusion, ketanserin (0.5 mg kg−1) modulates the hyperthermic actions of MDMA in mice. Although we cannot rule out additional actions at 5HT2‐receptors, the actions of ketanserin are consistent with α1‐adrenoceptor antagonism. There is no clear evidence from this study that 5HT2‐receptors mediate the hyperthermic response to MDMA.
Targeted enrichment and high‐resolution digital profiling of mitochondrial DNA deletions in human brain
Authors: Taylor Sean D. , Ericson Nolan G. , Burton Joshua N. , Prolla Tomas A. , Silber John R. , Shendure Jay , Bielas Jason H.
Published: August 2013

Due largely to the inability to accurately quantify and characterize de novo deletion events, the mechanisms underpinning the pathogenic expansion of mtDNA deletions in aging and neuromuscular disorders remain poorly understood. Here, we outline and validate a new tool termed ‘Digital Deletion Detection’ (3D) that allows for high‐resolution analysis of rare deletions occurring at frequencies as low as 1 × 10−8. 3D is a three‐step process that includes targeted enrichment for deletion‐bearing molecules, single‐molecule partitioning of genomes into thousands of droplets for direct quantification via droplet digital PCR, and breakpoint characterization using massively parallel sequencing. Using 3D, we interrogated over 8 billion mitochondrial genomes to analyze the age‐related dynamics of mtDNA deletions in human brain tissue. We demonstrate that the total deletion load increases with age, while the total number and diversity of unique deletions remain constant. Our data provide support for the hypothesis that expansion of pre‐existing mutations is the primary factor contributing to age‐related accumulation of mtDNA deletions.
Larval morphology of Neocamiarus kuscheli kuscheli Jeannel 1957 and Inocatops sp. (Coleoptera, Leiodidae, Camiarinae): the first modern descriptions of two members of the tribe Camiarini in comparison with other Camiarinae
Authors: Kilian Aleksandra , Ptak Maria
Published: August 2013

The first modern, detailed descriptions of mature larvae of the tribe Camiarini are presented. The larva of Neocamiarus kuscheli is redescribed, and the larva of an unidentified species of Inocatops is also described for the first time. Both are measured, illustrated and photographed. Morphological and chaetotaxic differences among mature larvae of both species are summarised. Inaccuracies of the previous description of the larva of N. kuscheli as well as unique features of each of the species are discussed. Larval characters of the described species are discussed with reference to other Camiarinae and Leiodidae and their gondwanian past.
Prognostic factors and outcomes for salvage surgery in patients with recurrent squamous cell carcinoma of the tongue
Authors: Goto Mitsuo , Hanai Nobuhiro , Ozawa Taijiro , Hirakawa Hitoshi , Suzuki Hidenori , Hyodo Ikuo , Kodaira Takeshi , Ogawa Tetsuya , Fujimoto Yasushi , Terada Akihiro , Kato Hisakazu , Hasegawa Yasuhisa
Published: August 2013

Aim

Recurrence rates of oral cancer following primary treatment have been reported in the range of 25–48%. However, salvage therapy remains a critical challenge to improving outcomes. Here, we investigated prognostic factors and outcomes for salvage surgery in patients with recurrent oral tongue squamous cell carcinoma (OTSCC).

Methods

We retrospectively reviewed patients who were referred to Aichi Cancer Center, Japan, for the treatment of recurrent OTSCC. All patients included in the present study had undergone salvage surgery. Data to identify the predictive value of prognostic factors were available from 69 patients. Prognostic factors were assessed using Cox's proportional hazards regression analysis. Differences in overall survival between groups of patients were assessed by the log–rank test.

Results

In all, 36 patients (52%) developed second recurrence or died, of which 21 (58%) occurred within 12 months of salvage surgery. Univariate analysis indicated that survival was significantly worse in patients with recurrent stage III or IV tumors, two or more positive cervical lymph nodes, levels IV or V positive cervical lymph nodes, extracapsular spread (ECS) of positive cervical lymph nodes and a disease‐free interval from initial treatment of less than 12 months. On multivariate analysis, ECS was an independent prognostic factor for overall survival after salvage surgery.

Conclusion

Neck status at the time of salvage surgery, particularly ECS is a significant prognostic factor for surgical salvage. Survival was also influenced by the stage of the recurrent tumor and disease‐free interval, suggesting that the biological features of recurrent tumors might impact on prognosis.
Association of plasma visfatin with risk of colorectal cancer: An observational study of Chinese patients
Authors: Chen Mingwei , Wang Youming , Li Yongxiang , Zhao Lili , Ye Shuai , Wang Shenyi , Yu Changjun , Xie Huijuan
Published: August 2013

Aim

To investigate the association between plasma visfatin levels and risk of early and advanced colorectal cancer (CRC).

Methods

In total, 358 CRC patients and 286 controls were enrolled. According to the T factor of the TNM system. cancer patients were divided into two subgroups: early and advanced cancer. Levels of visfatin, anthropometric and metabolic parameters, which were classified as low, medium, and high, based on the tertile distributions in the control group, were determined.

Results

The visfatin levels in patients with advanced and early cancer were higher than in controls (least significant difference test, P = 0.004 and 0.013, respectively). The patients in the highest tertile of visfatin concentration presented significantly higher odds for early and advanced CRC, adjusted for potential confounding factors (odds ratio 3.37; 95% CI, 1.93–8.37; P = 0.011; odds ratio 2.38; 95% CI: 1.82–8.35; P = 0.015, respectively). The visfatin level correlated significantly with waist:hip ratio (P < 0.05 for all) among case and control participants. Plasma visfatin levels in early and advanced CRC yielded a receiver operating characteristic curve area of 72 and 86%, respectively. The optimal sensitivity and specificity were 73% and 57% in discriminating between early CRC and normal controls while they were 76% and 68% in discriminating between advanced CRC and normal controls.

Conclusion

An increased level of visfatin was a strong risk factor for both early and advanced CRC in Chinese patients. Plasma visfatin levels might be a potential biomarker for CRC detection.
Poultry and fish intake and risk of esophageal cancer: A meta‐analysis of observational studies
Authors: Jiang Gengxi , Li Bailing , Liao Xiaohong , Zhong Chongjun
Published: August 2013

Aim

Mixed results regarding the association between white meat (including poultry and fish) intake and the risk of esophageal cancer (EC) have been reported. We performed a meta‐analysis to provide a quantitative assessment of this association.

Method(s)

Relevant studies were identified in MEDLINE until December 31, 2012. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were pooled with a random‐effects model.

Results

A total of 20 articles, including 3990 cases with EC, were included in this meta‐analysis. Compared to individuals with the lowest level of fish intake, individuals with the highest fish intake were found to have reduced risk of EC (SRRs = 0.69; 95% CIs: 0.57–0.85), while poultry intake was not associated with EC (SRRs = 0.83; 95% CIs: 0.62–1.12). Total fish consumption is associated with reduced esophageal squamous cell carcinoma (ESCC) risk, while poultry consumption was not associated with ESCC risk. Additionally, neither poultry nor fish consumption was associated with esophageal adenocarcinoma risk.

Conclusion(s)

Our results suggest that fish consumption may have a potential role in EC prevention, while poultry intake has no effect. However, because the majority of data was from case‐control studies, further well‐designed prospective studies are warranted.
Regulatory dendritic cell expression of MHCII and IL‐10 are jointly requisite for induction of tolerance in a murine model of OVA‐asthma
Authors: Huang H. , Dawicki W. , Lu M. , Nayyar A. , Zhang X. , Gordon J. R.
Published: August 2013

Background

Allergen‐presenting dendritic cells differentiated with IL‐10 (DC10) reverse the asthma phenotype in mice by converting their Th2 cells to regulatory T cells (Tregs). DC10 express elevated levels of IL‐10, but substantially reduced levels of MHCII and costimulatory molecules, so the relationships between these factors with each other and tolerogenicity have not been clearly elucidated.

Methods

We assessed the roles of these inputs in DC10 reversal of OVA‐associated asthma‐like disease by treating affected mice with OVA‐pulsed DC10 generated from wild‐type or IL‐10‐sufficient MHCII−/− or CD80/CD86−/− mice, or with MHCII‐intact IL‐10‐silenced DC10.

Results

IL‐10 silencing did not discernibly affect the cells' immunobiology (e.g., costimulatory molecules, chemokines), but it eliminated IL‐10 secretion and the cell's abilities to induce tolerance, as determined by assessments of airway hyper‐responsiveness, eosinophilia, and Th2 responses to recall OVA challenge. MHCII−/− DC10 expressed normal levels of IL‐10, but, nevertheless, were unable to induce allergen tolerance in asthma phenotype mice, while tolerance induced by CD80/CD86−/− DC10 was attenuated but not eliminated. We also assessed the induction of multiple Treg cell markers (e.g., ICOS, PD‐1, GITR) on pulmonary CD25+Foxp3+ cells in the treated mice. Wild‐type DC10 treatments upregulated expression of each marker, while neither IL‐10‐silenced nor MHCII−/− DC10 did so, and the CD80/86−/− DC10 induced an intermediate Treg cell activation phenotype.

Conclusion

Both IL‐10 and MCHII expression by DC10 are requisite, but not sufficient for tolerance induction, suggesting that DC10 and Th2 effector T cells must be brought together in a cognate fashion in order for their IL‐10 to induce tolerance.
Effect of retinoic acid on gene expression profiles of bovine intramuscular preadipocytes during adipogenesis
Authors: Mizoguchi Yasushi , Moriya Makoto , Taniguchi Daiki , Hasegawa Akira
Published: August 2013

To investigate genes involved in intramuscular adipogenesis in ruminants, 16 genes with dramatic variable expression were selected. These were selected from the differentiation‐ and proliferation‐phase libraries of our previous serial analysis of gene expression (SAGE) studies of a clonal bovine intramuscular preadipocyte (BIP) cell line. We harvested the BIP cells over 12 days after adipogenic stimulation with all‐trans retinoic acid (ATRA). Quantitative real‐time PCR confirmed the earlier SAGE study results of the expression patterns of 15 of the genes. On day 6, TG accumulation increased significantly in the BIP cells but was completely inhibited in the 3T3‐L1 cells (the monogastric reference). ATRA enhanced expression levels of six genes whereas it suppressed expression of eight genes on day 3 of adipogenesis in the BIP cells. Forty‐eight hours after transfection, the messenger RNA expression level of the adipose differentiation‐related protein (ADFP), encoded by one of the upregulated genes, in the ADFP small interference RNA (siRNA)‐transfected cells was 3.5% of that in negative control‐transfected cells. Also, 6 days after induction the TG level in the ADFP siRNA‐transfected cells was 21.8% lower than that in negative control‐transfected cells. This analysis of gene expression profiles after ATRA treatment will contribute to our understanding of the molecular mechanisms involved in bovine intramuscular adipogenesis.
Normal Human Variation: Refocussing the Enhancement Debate
Authors: Kahane Guy , Savulescu Julian
Published: August 2013

This article draws attention to several common mistakes in thinking about biomedical enhancement, mistakes that are made even by some supporters of enhancement. We illustrate these mistakes by examining objections that John Harris has recently raised against the use of pharmacological interventions to directly modulate moral decision‐making. We then apply these lessons to other influential figures in the debate about enhancement. One upshot of our argument is that many considerations presented as powerful objections to enhancement are really strong considerations in favour of biomedical enhancement, just in a different direction. Another upshot is that it is unfortunate that much of the current debate focuses on interventions that will radically transform normal human capacities. Such interventions are unlikely to be available in the near future, and may not even be feasible. But our argument shows that the enhancement project can still have a radical impact on human life even if biomedical enhancement operated entirely within the normal human range.
A Decision‐Theory Approach to Interpretable Set Analysis for High‐Dimensional Data
Authors: Boca Simina M. , Bravo Héctor Corrada , Caffo Brian , Leek Jeffrey T. , Parmigiani Giovanni
Published: August 2013

A key problem in high‐dimensional significance analysis is to find pre‐defined sets that show enrichment for a statistical signal of interest; the classic example is the enrichment of gene sets for differentially expressed genes. Here, we propose a new decision‐theory approach to the analysis of gene sets which focuses on estimating the fraction of non‐null variables in a set. We introduce the idea of “atoms,” non‐overlapping sets based on the original pre‐defined set annotations. Our approach focuses on finding the union of atoms that minimizes a weighted average of the number of false discoveries and missed discoveries. We introduce a new false discovery rate for sets, called the atomic false discovery rate (afdr), and prove that the optimal estimator in our decision‐theory framework is to threshold the afdr. These results provide a coherent and interpretable framework for the analysis of sets that addresses the key issues of overlapping annotations and difficulty in interpreting p values in both competitive and self‐contained tests. We illustrate our method and compare it to a popular existing method using simulated examples, as well as gene‐set and brain ROI data analyses.
Pre‐diagnosis cigarette smoking and overall survival in non‐Hodgkin lymphoma
Authors: Ollberding Nicholas J. , Evens Andrew M. , Aschebrook‐Kilfoy Briseis , Caces Donne Bennett D. , Weisenburger Dennis D. , Smith Sonali M. , Chiu Brian C.‐H.
Published: August 2013

We examined whether smoking prior to non‐Hodgkin lymphoma (NHL) diagnosis was associated with overall survival (OS) and conducted a meta‐analysis to assess the evidence relating pre‐diagnosis cigarette smoking with OS. Among 523 NHL patients, worse OS was suggested for greater pre‐diagnostic smoking habits when compared to never smokers. In the meta‐analysis (n = 5 patient populations), inferior OS was observed for greater number of cigarettes smoked per day, years of cigarette smoking, and pack‐years of cigarette smoking. The inferior survival was more pronounced for follicular than for diffuse large B cell lymphoma. Pre‐diagnosis cigarette smoking may adversely impact the survival of NHL patients.
National prospective study on the use of local haemostatic agents during partial nephrectomy
Authors: Lang Herve , Mouracade Pascal , Gimel Pierre , Bernhard Jean C. , Pignot Geraldine , Zini Laurent , Crepel Maxime , Rigaud Jerome , Salomon Laurent , Bellec Laurent , Vaessen Christophe , Roupret Morgan , Jung Jean L. , Mourey Eric , Martin Xavier , Bigot Pierre , Bruyère Franck , Berger Julien , Ansieau Jean P. , Salome Franck , Hubert Jacques , Pfister Christian , Trifard François , Gigante Marc , Baumert Herve , Méjean Arnaud , Patard Jean J.
Published: August 2013

Objective

To assess the use of local haemostatic agents (HAs) in a prospective multicentre large series of partial nephrectomies (PNs).

Patients and Methods

Prospective National Observational Registry on the Practices of Haemostasis in Partial Nephrectomy (NEPHRON): the study was conducted in 54 French urological centres from 1 June to 31 December 2010.

In all, 570 consecutive patients undergoing a PN were enrolled in this study in a prospective manner. The data was collected prospectively via an electronic case‐report form: five different sheets were included for preoperative, perioperative, postoperative and follow‐up data respectively. Information related to haemostasis was analysed.

Results

The median patient age was 60 years and the mean (range) tumour size was 3.68 (0.19–15) cm.

An HA was primarily used in 71.4% of patients, with a statistically significant difference among surgical approaches (P = 0.024).

In 91.8% of cases, a single use of a HA was sufficient for achieving haemostasis. The HA was used either alone (13.9%) or in association with sutures (80.3%).

One or more additional haemostatic action(s) was needed in 12.3% of the cases.

When comparing patients who received a HA with those who did not receive a HA, there was no statistical difference between the groups for tumour size (P = 0.542), collecting system drainage (P = 0.538), hospital stay (P = 0.508), operation time (P = 0.169), blood loss (P = 0.387) or transfusion rate (P = 0.713).

Conclusion

HAs are widely used by urologists during PN. Progress is needed for standardising HA application, especially for the timing of application. For the time being, the role of the HA in nephron‐sparing surgery is still to be evaluated.
Differences in the localization of the adenomatous polyposis coli‐Asef/Asef2 complex between adenomatous polyposis coli wild‐type and mutant cells
Authors: Kawasaki Yoshihiro , Furukawa Shiori , Sato Rina , Akiyama Tetsu
Published: August 2013

The tumor suppressor adenomatous polyposis coli (APC) is mutated in familial adenomatous polyposis and in many sporadic colorectal tumors. Adenomatous polyposis coli is known to negatively regulate Wnt signaling by inducing the degradation of β‐catenin. Adenomatous polyposis coli also interacts with the guanine nucleotide exchange factors Asef and Asef2 and stimulates their activity, thereby regulating cell adhesion and migration. Here we show that in confluent, non‐motile MDCK II cells, Asef/Asef2 are colocalized with APC at the sites of cell–cell adhesion at the apical and junctional levels. In contrast, in colorectal tumor cells containing mutated APC, significant amounts of Asef/Asef2 and the truncated mutant APCs are localized mainly in the cytoplasm. These results suggest that localization of the Asef/Asef2‐APC complex at the sites of cell–cell contact is critical for the regulation of cell adhesion, and that the aberrant subcellular localization of these complexes in colorectal tumor cells may contribute to the cell's aberrant adhesive and migratory properties.
Catheter Ablation of Atrial Flutter in Patients With Left Ventricular Assist Device Improves Symptoms of Right Heart Failure
Authors: Hottigoudar Rashmi U. , Deam Allen G. , Birks Emma J. , McCants Kelly C. , Slaughter Mark S. , Gopinathannair Rakesh
Published: August 2013

Persistent atrial flutter (AFL) in left ventricular assist device (LVAD) recipients can result in loss of AV synchrony, impaired ventricular filling and right heart failure (RHF). The authors report the largest series of HeartMate II (HMII) patients who developed AFL with decompensated RHF, which successfully resolved with AFL ablation. Eight patients with HMII LVAD (mean age, 57±12 years) had medically refractory AFL, with 7 developing de novo AFL after LVAD implant (onset range, 2 days–22 months post‐implant). Three patients developed recurrent syncope, 2 had inappropriate implantable cardioverter‐defibrillator shocks, and 6 had new or escalating need for inotropes. All had features of decompensated RHF. Seven patients underwent electrophysiology testing where mapping confirmed typical counterclockwise AFL (mean AFL cycle length, 252±49 ms) and radiofrequency ablation of cavotricuspid isthmus restored sinus rhythm in all patients. Complete resolution of symptoms and signs of RHF with improved quality of life were noted in all. No procedural complications were noted. During a mean follow‐up of 9±5 months, all patients remained free of atrial flutter. Catheter ablation of AFL in LVAD patients is safe and highly effective, resulting in immediate and significant improvement in symptoms of RHF, and should be considered first‐line therapy for AFL in these patients.
Prognosis of Morbid Obesity Patients With Advanced Heart Failure
Authors: Nagarajan Vijaiganesh , Cauthen Clay A. , Starling Randall C. , Tang Wai Hong Wilson
Published: August 2013

Obese patients have been noted to have better prognosis in many conditions including heart failure. We hypothesize that this favorable prognosis for obesity may not be seen in patients with morbid obesity and advanced heart failure. A total of 501 consecutive patients with advanced heart failure referred for heart transplant evaluation to the Cleveland Clinic were studied. Patients were categorized into 3 groups based on their body mass index score as nonobese (≤30 kg/m2), obese (30.1–40 kg/m2), and morbidly obese (≥40 kg/m2). There were fewer cardiovascular risk factors in the morbidly obese group. Unadjusted event‐free survival rates were 48.4%, 57.4%, and 28.6% in the nonobese, obese, and morbidly obese groups, respectively (P=.02). In univariate analysis, both the nonobese group (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.09–1.91; P=.01) and the morbidly obese group (HR, 2.46; 95% CI, 1.40–4.30; P=.002) had significantly higher risk of all‐cause mortality/transplantation compared with the obese group. This difference persisted in multivariate analysis after adjustment for confounding factors. Our study re‐emphasizes the presence of an obesity paradox even in patients with very advanced heart failure. This favorable prognosis, however, may not be relevant in patients with morbidly obesity. Cardiovascular risk factors may not contribute to this phenomenon
Alternatives to islet transplantation: future cell sources of beta‐like cells
Authors: Bruns Helge , Schultze Daniel , Schemmer Peter
Published: August 2013

Cell transplantation is a treatment option for diabetes, metabolic liver disease in children, and leukemia. Except for the latter indication, solid organ transplantation is one of the available therapies but can be replaced by cell transplantation. However, due to the limited amount of cells that can be transplanted and due to rejection, results of cell transplants are still inferior to solid organ transplantation; there is a general shortage of donor organs, and cell isolation is limited to organs which cannot be transplanted as a whole for anatomic reasons. Therefore, alternatives to islets and beta cells are needed. There are some cells which can be generated from the recipient and would not be rejected; still, immunosuppression would be required to prevent reoccurrence of type I diabetes unless durable tolerance to beta cells could be induced. Generating beta cells for transplant from the recipient would help to overcome the lack of available organs. Moreover, understanding the underlying mechanisms of differentiation of these cells into beta‐like cells would deepen our understanding of both pathophysiology and development of diabetes mellitus type I. This article examines embryonal stem cells, induced pluripotent cells, mesenchymal stromal cells, and hepatocytes as potential alternatives to beta‐cell transplantation.
Efficacy, usability and sequence of operations of a workflow‐integrated algorithm for basal–bolus insulin therapy in hospitalized type 2 diabetes patients
Authors: Mader J. K. , Neubauer K. M. , Schaupp L. , Augustin T. , Beck P. , Spat S. , Höll B. , Treiber G. M. , Fruhwald F. M. , Pieber T. R. , Plank J.
Published: August 2013

Aims

To evaluate glycaemic control and usability of a workflow‐integrated algorithm for basal–bolus insulin therapy in a proof‐of‐concept study to develop a decision support system in hospitalized patients with type 2 diabetes.

Methods

In this ward‐controlled study, 74 type 2 diabetes patients (24 female, age 68 ± 11 years, HbA1c 8.7 ± 2.4% and body mass index 30 ± 7) were assigned to either algorithm‐based treatment with a basal–bolus insulin therapy or to standard glycaemic management. Algorithm performance was assessed by continuous glucose monitoring and staff's adherence to algorithm‐calculated insulin dose.

Results

Average blood glucose levels (mmol/l) in the algorithm group were significantly reduced from 11.3 ± 3.6 (baseline) to 8.2 ± 1.8 (last 24 h) over a period of 7.5 ± 4.6 days (p < 0.001). The algorithm group had a significantly higher percentage of glucose levels in the ranges from 5.6 to 7.8 mmol/l (target range) and 3.9 to 10.0 mmol/l compared with the standard group (33 vs. 23% and 73 vs. 53%, both p < 0.001). Physicians' adherence to the algorithm‐calculated total daily insulin dose was 95% and nurses' adherence to inject the algorithm‐calculated basal and bolus insulin doses was high (98 and 93%, respectively). In the algorithm group, significantly more glucose values <3.9 mmol/l were detected in the afternoon relative to other times (p < 0.05), a finding mainly related to pronounced morning glucose excursions and requirements for corrective bolus insulin at lunch.

Conclusions

The workflow‐integrated algorithm for basal–bolus therapy was effective in establishing glycaemic control and was well accepted by medical staff. Our findings support the implementation of the algorithm in an electronic decision support system.
Diabetic foot infections: state‐of‐the‐art
Authors: Uçkay I. , Gariani K. , Pataky Z. , Lipsky B. A.
Published: August 2013

Foot infections are frequent and potentially devastating complications of diabetes. Unchecked, infection can progress contiguously to involve the deeper soft tissues and ultimately the bone. Foot ulcers in people with diabetes are most often the consequence of one or more of the following: peripheral sensory neuropathy, motor neuropathy and gait disorders, peripheral arterial insufficiency or immunological impairments. Infection develops in over half of foot ulcers and is the factor that most often leads to lower extremity amputation. These amputations are associated with substantial morbidity, reduced quality of life and major financial costs. Most infections can be successfully treated with optimal wound care, antibiotic therapy and surgical procedures. Employing evidence‐based guidelines, multidisciplinary teams and institution‐specific clinical pathways provides the best approach to guide clinicians through this multifaceted problem. All clinicians regularly seeing people with diabetes should have an understanding of how to prevent, diagnose and treat foot infections, which requires familiarity with the pathophysiology of the problem and the literature supporting currently recommended care.
A direct comparison of long‐ and short‐acting GLP‐1 receptor agonists (taspoglutide once weekly and exenatide twice daily) on postprandial metabolism after 24 weeks of treatment
Authors: Gastaldelli A. , Balas B. , Ratner R. , Rosenstock J. , Charbonnel B. , Bolli G. B. , Boldrin M. , Balena R.
Published: August 2013

Aims

T‐emerge 2 was a randomized, open‐label, 24‐week trial comparing subcutaneous taspoglutide 10 mg weekly (Taspo10), taspoglutide 20 mg weekly (Taspo20; titrated after 4 weeks of Taspo10), with exenatide 10 mcg BID (Exe; after 4 weeks of Exe 5 mcg) in patients inadequately controlled on metformin, a thiazolidinedione, or both. T‐emerge 2 showed that once‐weekly Taspo provided better glycaemic control than Exe. This report focuses on a subset of T‐emerge 2 participants undergoing a standardized liquid meal comparing Taspo to Exe, which has been previously shown to lower postprandial glucose.

Methods

Meal tolerance tests (MTT) were performed at baseline and at week 24 in a subset of Taspo10, Taspo20 and Exe patients (n = 42, 39 and 67, respectively). Blood samples for glucose, insulin, glucagon and C‐peptide were obtained before and after (30, 60, 90, 120 and 180 min) ingestion of a standardized liquid meal.

Results

The 2‐h postprandial, mean 0–3 h and iAUC0‐3 h glucose during the MTT was reduced to a similar extent in all groups and the time profile of the postprandial glucose showed a similar pattern. Taspo10 and Taspo20, but not Exe, significantly increased insulin from baseline (both mean and iAUC0‐3 h). Although changes from baseline in C‐peptide were not significant within any treatment group, the mean change from baseline (both mean 0–3 h and iAUC0‐3 h) was significantly increased in Taspo10 vs. Exe. Mean glucagon showed significant decreases in all groups.

Conclusion

Taspoglutide and Exe improved postprandial glucose tolerance to a similar extent but possibly with different intimate mechanisms.
Improving Transparency and Accountability in the Budget Process: An Assessment of Recent Initiatives
Authors: Carlitz Ruth
Published: August 2013

In recent decades budget transparency has come to be seen as a pillar of good governance. This article reviews budget‐related transparency and accountability initiatives (TAIs) to analyse their impact. While there are many examples of success in terms of budget processes around the world being opened up to greater participation and scrutiny, there is no single recipe for creating a successful initiative to enhance transparency and accountability in the budget process. A consistent set of factors does, however, appear across those TAIs defined as successful in various ways. These include building horizontal and vertical alliances between stakeholders, the production of legitimate information, legal empowerment and international support.
Aid Transparency and Accountability: ‘Build It and They'll Come’?1
Authors: McGee Rosemary
Published: August 2013

Concerns about the transparency of aid have become more prominent against a recent backdrop of donor commitments to increase aid effectiveness. Innovative approaches to providing more and better information about aid have been developed. This article explores the contemporary focus on aid transparency in the context of longer‐standing concerns over accountable aid. It finds that the links between inputs, outputs and impacts in aid transparency and accountability initiatives are often not articulated or well understood, and that the link between aid transparency and accountable aid is barely addressed. Future attempts to develop effective aid TAIs need to take full account of the diverse motivations, approaches and actors involved in their – often implicit – theories of change, in particular, the citizens of aid‐recipient countries.
Does dimethyl sulfoxide increase protein immunomarking efficiency for dispersal and predation studies?
Authors: Williams Livy , Hagler James R. , Tonkel Kirk C.
Published: August 2013

Marking biological control agents facilitates studies of dispersal and predation. This study examines the effect of a biological solvent, dimethyl sulfoxide (DMSO), on retention of immunoglobulin G (IgG) protein solutions applied to Diorhabda carinulata (Desbrochers) (Coleoptera: Chrysomelidae), an important biological control agent of saltcedar, either internally by feeding them protein‐labeled foliage or externally by immersing them in a protein solution. In addition, we determined whether internally or externally marked DMSO‐IgG labels could be transferred via feeding from marked D. carinulata to its predator, Perillus bioculatus (Fabricius) (Heteroptera: Pentatomidae). The presence of rabbit and chicken IgG proteins was detected by IgG‐specific enzyme‐linked immunosorbent assays (ELISA). DMSO‐IgG treatments showed greater label retention than IgG treatments alone, and this effect was stronger for rabbit IgG than for chicken IgG. Fourteen days after marking, beetles immersed in rabbit IgG showed 100% internal retention of label, whereas beetles immersed in chicken IgG showed 65% internal retention. Immersion led to greater initial (time 0) label values, and longer label retention, than feeding beetles labeled foliage. The DMSO‐IgG label was readily transferred to P. bioculatus after feeding on a single marked prey insect. This investigation shows that addition of DMSO enhances retention of IgG labels, and demonstrates that protein marking technology has potential for use in dispersal and predator–prey studies with D. carinulata. Moreover, our observation of P. bioculatus feeding on D. carinulata is, to our knowledge, a new predator–prey association for the stink bug.
Epilepsy therapy development: Technical and methodologic issues in studies with animal models
Authors: Galanopoulou Aristea S. , Kokaia Merab , Loeb Jeffrey A. , Nehlig Astrid , Pitkänen Asla , Rogawski Michael A. , Staley Kevin J. , Whittemore Vicky H. , Edward Dudek F.
Published: August 2013

The search for new treatments for seizures, epilepsies, and their comorbidities faces considerable challenges. This is due in part to gaps in our understanding of the etiology and pathophysiology of most forms of epilepsy. An additional challenge is the difficulty in predicting the efficacy, tolerability, and impact of potential new treatments on epilepsies and comorbidities in humans, using the available resources. Herein we provide a summary of the discussions and proposals of the Working Group 2 as presented in the Joint American Epilepsy Society and International League Against Epilepsy Translational Workshop in London (September 2012). We propose methodologic and reporting practices that will enhance the uniformity, reliability, and reporting of early stage preclinical studies with animal seizure and epilepsy models that aim to develop and evaluate new therapies for seizures or epilepsies, using multidisciplinary approaches. The topics considered include the following: (1) implementation of better study design and reporting practices; (2) incorporation in the study design and analysis of covariants that may influence outcomes (including species, age, sex); (3) utilization of approaches to document target relevance, exposure, and engagement by the tested treatment; (4) utilization of clinically relevant treatment protocols; (5) optimization of the use of video‐electroencephalography (EEG) recordings to best meet the study goals; and (6) inclusion of outcome measures that address the tolerability of the treatment or study end points apart from seizures. We further discuss the different expectations for studies aiming to meet regulatory requirements to obtain approval for clinical testing in humans. Implementation of the rigorous practices discussed in this report will require considerable investment in time, funds, and other research resources, which may create challenges for academic researchers seeking to contribute to epilepsy therapy discovery and development. We propose several infrastructure initiatives to overcome these barriers.
Issues related to development of new antiseizure treatments
Authors: Wilcox Karen S. , Dixon‐Salazar Tracy , Sills Graeme J. , Ben‐Menachem Elinor , Steve White H. , Porter Roger J. , Dichter Marc A. , Moshé Solomon L. , Noebels Jeffrey L. , Privitera Michael D. , Rogawski Michael A.
Published: August 2013

This report represents a summary of the discussions led by the antiseizure treatment working group of the International League Against Epilepsy (ILAE)/American Epilepsy Society (AES) Working Groups joint meeting in London (London Meeting). We review here what is currently known about the pharmacologic characteristics of current models of refractory seizures, both for adult and pediatric epilepsy. In addition, we address how the National Institute of Neurological Disorders and Stroke (NINDS)–funded Anticonvulsant Screening Program (ASP) is evolving to incorporate appropriate animal models in the search for molecules that might be sufficiently novel to warrant further pharmacologic development. We also briefly address what we believe is necessary, going forward, to achieve the goal of stopping seizures in all patients, with a call to arms for funding agencies, the pharmaceutical industry, and basic researchers.
Issues related to symptomatic and disease‐modifying treatments affecting cognitive and neuropsychiatric comorbidities of epilepsy
Authors: Brooks‐Kayal Amy R. , Bath Kevin G. , Berg Anne T. , Galanopoulou Aristea S. , Holmes Gregory L. , Jensen Frances E. , Kanner Andres M. , O'Brien Terence J. , Whittemore Vicky H. , Winawer Melodie R. , Patel Manisha , Scharfman Helen E.
Published: August 2013

Many symptoms of neurologic or psychiatric illness—such as cognitive impairment, depression, anxiety, attention deficits, and migraine—occur more frequently in people with epilepsy than in the general population. These diverse comorbidities present an underappreciated problem for people with epilepsy and their caregivers because they decrease quality of life, complicate treatment, and increase mortality. In fact, it has been suggested that comorbidities can have a greater effect on quality of life in people with epilepsy than the seizures themselves. There is increasing recognition of the frequency and impact of cognitive and behavioral comorbidities of epilepsy, highlighted in the 2012 Institute of Medicine report on epilepsy. Comorbidities have also been acknowledged, as a National Institutes of Health (NIH) Benchmark area for research in epilepsy. However, relatively little progress has been made in developing new therapies directed specifically at comorbidities. On the other hand, there have been many advances in understanding underlying mechanisms. These advances have made it possible to identify novel targets for therapy and prevention. As part of the International League Against Epilepsy/American Epilepsy Society workshop on preclinical therapy development for epilepsy, our working group considered the current state of understanding related to terminology, models, and strategies for therapy development for the comorbidities of epilepsy. Herein we summarize our findings and suggest ways to accelerate development of new therapies. We also consider important issues to improve research including those related to methodology, nonpharmacologic therapies, biomarkers, and infrastructure.
Epilepsy biomarkers
Authors: Engel Jerome , Pitkänen Asla , Loeb Jeffrey A. , Edward Dudek F. , Bertram Edward H. , Cole Andrew J. , Moshé Solomon L. , Wiebe Samuel , Jensen Frances E. , Mody Istvan , Nehlig Astrid , Vezzani Annamaria
Published: August 2013

A biomarker is defined as an objectively measured characteristic of a normal or pathologic biologic process. Identification and proper validation of biomarkers of epileptogenesis (the development of epilepsy) and ictogenesis (the propensity to generate spontaneous seizures) might predict the development of an epilepsy condition; identify the presence and severity of tissue capable of generating spontaneous seizures; measure progression after the condition is established; and determine pharmacoresistance. Such biomarkers could be used to create animal models for more cost‐effective screening of potential antiepileptogenic and antiseizure drugs and devices, and to reduce the cost of clinical trials by enriching the trial population, and acting as surrogate markers to shorten trial duration. The objectives of the biomarker subgroup for the London Workshop were to define approaches for identifying possible biomarkers for these purposes. Research to identify reliable biomarkers may also reveal underlying mechanisms that could serve as therapeutic targets for the development of new antiepileptogenic and antiseizure compounds.
Assessment of the equine neonate in ambulatory practice
Authors: Austin S. M.
Published: August 2013

The ambulatory practitioner is usually the first to evaluate the equine neonate and must assess the foal and determine its health status. If there is suspicion of one or more abnormalities, then the ambulatory veterinarian must initiate appropriate treatment and determine if the foal can be successfully treated in the field or should be referred to a specialty hospital. This article will describe the examination procedure including an accurate history, a comprehensive physical examination, laboratory evaluation and application of point‐of‐care diagnostics. The initial examination is the basis for the correct determination of health or illness and informing the owner of the correct course of action for the neonatal foal.
Evasin‐4, a tick‐derived chemokine‐binding protein with broad selectivity can be modified for use in preclinical disease models
Authors: Déruaz Maud , Bonvin Pauline , Severin India C. , Johnson Zoë , Krohn Sonja , Power Christine A. , Proudfoot Amanda E. I.
Published: August 2013

Rhipicephalus sanguineus, the common brown dog tick, produces several chemokine‐binding proteins which are secreted into the host in its saliva to modulate the host response during feeding. Two of these demonstrate very restricted selectivity profiles. Here, we describe the characterization of the third, which we named Evasin‐4. Evasin‐4 was difficult to produce recombinantly using its native signal peptide in HEK cells, but expressed very well using the urokinase‐type plasminogen activator signal peptide. Using SPR, Evasin‐4 was shown to bind most CC chemokines. Investigation of the neutralization properties by inhibition of chemokine‐induced chemotaxis showed that binding and neutralization did not correlate in all cases. Two major anomalies were observed: no binding was observed to CCL2 and CCL13, yet Evasin‐4 was able to inhibit chemotaxis induced by these chemokines. Conversely, binding to CCL25 was observed, but Evasin‐4 did not inhibit CCL25‐induced chemotaxis. Size‐exclusion chromatography confirmed that Evasin‐4 forms a complex with CCL2 and CCL18. In accordance with the standard properties of unmodified small proteins, Evasin‐4 was rapidly cleared following in vivo administration. To enhance the in vivo half‐life and optimize its potential as a therapeutic agent, Fc fusions of Evasin‐4 were created. Both the N‐ and C‐terminal fusions were shown to retain binding activity, with the C‐terminal fusion showing a modest reduction in potency.
Length variation in the mouse mitochondrial tRNAArg DHU loop size promotes oxidative phosphorylation functional differences
Authors: Moreno‐Loshuertos Raquel , Pérez‐Martos Acisclo , Fernández‐Silva Patricio , Enríquez José Antonio
Published: August 2013

The efficiency of the cellular oxidative phosphorylation system was recently shown to be modulated by common mitochondrial tRNAArg haplotypes. The molecular mechanism by which some mt‐Tr haplotypes induce these functional differences remains undetermined. Common polymorphisms in mouse mt‐Tr genes affect the size of the dihydrouridine loop in the mature tRNA, producing loops of between five and seven nucleotides, the largest being a rare variant among mammals. Here, we analyzed a new mt‐Tr variant identified in C3H mice, and found that it is mitochondrial tRNA loop size, but not the specific sequence, that is responsible for the observed differences in cellular respiration. We further found that the sensitivity of mitochondrial protein synthesis to specific inhibitors is dependent on the mt‐Tr gene haplotype, and confirmed that the differences in oxidative phosphorylation performance are masked by a reactive oxygen species‐induced compensatory increase in mitochondrial biogenesis.