bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular risk factors associated with age‐related macular degeneration: the Tromsø Study
Authors: Erke Maja G , Bertelsen Geir , Peto Tunde , Sjølie Anne K , Lindekleiv Haakon , Njølstad Inger
Published: January 2014

Purpose

To examine associations between cardiovascular risk factors and age‐related macular degeneration (AMD).

Methods

A population‐based, cross‐sectional study of Caucasians aged 65–87 years was conducted in Norway in 2007/2008. Retinal photographs were graded for AMD. Multivariable logistic regression analyses were performed based on questionnaires addressing habits of smoking, alcohol consumption, physical activity, health and medication; and physical examination comprising anthropometric measurements, blood pressure and blood sampling. Cardiovascular disease status was obtained from a validated end‐point registry.

Results

Gradable photographs were available for 2631 participants, of whom 92 (3.5%) subjects had late AMD. In the multivariable analysis of late AMD, significant interactions were found between sex and the variables age, triglyceride level, use of lipid‐lowering drugs and physical exercise. Current daily smoking was significantly related to late AMD in both sexes (odds ratio (OR) 4.06, 95% confidence interval (CI) 1.69–9.76 and OR 3.59, 95% CI 1.17–11.04, women and men, respectively) compared with never smokers. Higher number of pack years was associated with the presence of large drusen (>125 μm) (OR 1.04, 95% CI 1.01–1.09 per 5 years). Higher systolic blood pressure (OR 1.06, 95% CI 1.01–1.12 per 5 mmHg), overweight (OR 2.87, 95% CI 1.13–7.29) and obesity (OR 2.92, 95% CI 1.06–8.03), physical exercise duration (OR 0.41, 95% 0.18–0.96 for 30 min or more compared with less) and frequency (OR 0.46, 95% CI 0.23–0.92 for weekly or more often compared to less) were associated with late AMD in women only.

Conclusions

Smoking was strongly associated with AMD, in line with results from other populations. Also, late AMD was related to higher systolic blood pressure, physical inactivity, overweight and obesity in women.
Vascular considerations in glaucoma patients of African and European descent
Authors: Huck Andrew , Harris Alon , Siesky Brent , Kim Nathaniel , Muchnik Michael , Kanakamedala Priyanka , Amireskandari Annahita , Abrams‐Tobe Leslie
Published: January 2014

Glaucoma is the leading cause of blindness in individuals of African descent (AD). While open‐angle glaucoma (OAG) disproportionately affects individuals of AD compared with persons of European descent (ED), the physiological mechanisms behind this disparity are largely unknown. The more rapid progression and greater severity of the disease in persons of AD further raise the concern for identifying these underlying differences in disease pathophysiology between AD and ED glaucoma patients. Ocular structural differences between AD and ED patients, including larger optic disc area, cup:disc ratio and thinner corneas, have been found. AD individuals are also disproportionately affected by systemic vascular diseases, including hypertension, cardiovascular disease, stroke and diabetes mellitus. Abnormal ocular blood flow has been implicated as a risk factor for glaucoma, and pilot research is beginning to identify localized ocular vascular differences between AD and ED OAG patients. Given the known systemic vascular deficits and the relationship between glaucoma and ocular blood flow, exploring these concepts in terms of glaucoma risk factors may have a significant impact in elucidating the mechanisms behind the disease disparity in the AD population.
Prediction of Skin Sensitizers using Alternative Methods to Animal Experimentation
Authors: Johansson Henrik , Lindstedt Malin
Published: January 2014

Regulatory frameworks within the European Union demand that chemical substances are investigated for their ability to induce sensitization, an adverse health effect caused by the human immune system in response to chemical exposure. A recent ban on the use of animal tests within the cosmetics industry has led to an urgent need for alternative animal‐free test methods that can be used for assessment of chemical sensitizers. To date, no such alternative assay has yet completed formal validation. However, a number of assays are in development and the understanding of the biological mechanisms of chemical sensitization has greatly increased during the last decade. In this MiniReview, we aim to summarize and give our view on the recent progress of method development for alternative assessment of chemical sensitizers. We propose that integrated testing strategies should comprise complementary assays, providing measurements of a wide range of mechanistic events, to perform well‐educated risk assessments based on weight of evidence.
High‐Content Analysis/Screening for Predictive Toxicology: Application to Hepatotoxicity and Genotoxicity
Authors: Persson Mikael , Løye Anni F. , Jacquet Mélanie , Mow Natacha S. , Thougaard Annemette V. , Mow Tomas , Hornberg Jorrit J.
Published: January 2014

High‐content imaging/analysis has emerged as a powerful tool for predictive toxicology as it can be used for identifying and mitigating potential safety risks during drug discovery. By careful selection of end‐points, some cellular assays can show better predictivity than routine animal toxicity testing for certain adverse events. Here, we present the perhaps most utilized high‐content screening assays for predictive toxicology in the pharmaceutical industry. Multi‐parametric imaging of cell health in simple and cost‐effective model systems can be used to predict human hepatotoxicity and elucidate mechanisms of toxicity, and imaging of bile salt transport inhibition in sandwich‐cultured hepatocytes can be used to predict cholestasis‐inducing compounds. Imaging of micronuclei formation in simple cell models can be used to detect genotoxic potential and elucidate anuegenic or clastogenic mode of actions. The hope is that application of these relatively predictive assays during drug discovery will reduce toxicity and safety‐related attrition of drug development programmes at later stages.
A Lectin from Spatholobus parviflorus Inhibits Aspergillus flavus α‐Amylase: Enzyme Kinetics and Thermodynamic Studies
Authors: Tintu Ignatius , Abhilash Joseph , Dileep Kalarickal V. , Augustine Anu , Haridas Madathilkovilakath , Sadasivan Chittalakkottu
Published: January 2014

Aspergillus flavus is a commonly found fungal pathogen which produces structurally related and highly toxic secondary metabolites, aflatoxins. It has been proposed that α‐amylase inhibitors may limit the ability of the fungus to produce aflatoxins. Hence, this enzyme is a potent target for the development of antifungal agents. In this study, it was found that Spatholobus parviflorus seed lectin (SPL) can inhibit the growth of A. flavus with a MIC value of 1.5 mg/mL. The enzyme kinetics, molecular modeling and isothermal titration calorimetric studies suggest that SPL can inhibit α‐amylase with Ki value of 0.0042 mm. Hence, it is suggested that the antifungal activity of SPL might be partly due to its ability to inhibit the enzyme α‐amylase.
Lead Optimization on Conventional Non‐Steroidal Anti‐Inflammatory Drugs: An Approach to Reduce Gastrointestinal Toxicity
Authors: Narsinghani Tamanna , Sharma Rajesh
Published: January 2014

Non‐steroidal anti‐inflammatory drugs are among the most widely used therapeutics, primarily for the treatment for pain and inflammation. Prostaglandins mediate a number of characteristic features of the body's response to tissue injury or inflammation. These outstanding effects include their cytoprotective properties in the gastrointestinal tract and control of renal functions in the kidney. Non‐steroidal anti‐inflammatory drugs exert their anti‐inflammatory and antipyretic effects by blocking the production of prostanoids from arachidonic acid through inhibition ofcyclooxygenase enzyme. Classic non‐steroidal anti‐inflammatory drugs such as meclofenamic acid and indomethacin inhibit both isoforms of cyclooxygenase non‐selectively or with low selectivity, exerting their anti‐inflammatory activity via inhibiting cyclooxygenase‐2, and their deleterious side‐effects by inhibiting cyclooxygenase‐1. To provide an effective treatment for inflammatory disorders, the design of novel non‐steroidal anti‐inflammatory drugs is aimed at obtaining new drugs, devoid of the side‐effects commonly associated with conventional non‐steroidal anti‐inflammatory drugs. Several approaches have been explored to counteract the gastric damaging effects of these drugs. The chemical modification of non‐steroidal anti‐inflammatory drugs is aimed at improving their safety profile, where several studies have described the derivatization of the carboxylate function of non‐steroidal anti‐inflammatory drugs with less acidic analogs, which resulted in an increased anti‐inflammatory activity with reduced ulcerogenicity. The present review explores the possible ways aimed to reduce ulcerogenicity.
Decision making on detection and triage of oral mucosa lesions in community dental practices: screening decisions and referral
Authors: Laronde Denise M. , Williams P. M. , Hislop T. G. , Poh Catherine , Ng Samson , Zhang Lewei , Rosin Miriam P.
Published: January 2014

Oral cancer is a substantial, often unrecognized issue globally, with close to 300 000 new cases reported annually. It is a management conundrum: a cancer site that is easily examined; yet more than 40% of oral cancers are diagnosed at a late stage when prognosis is poor and treatment can be devastating. Opportunistic screening within the dental office could lead to earlier diagnosis and intervention with improved survival.

Objective

To describe how clinicians make decisions about referral based on the risk classification of the lesion.

Methods

Eighteen dentists from 15 dental offices participated in a 1‐day workshop on oral cancer screening. Participants then screened patients (medical history, conventional oral exam, fluorescent visualization examination) in‐office for 11 months, triaging patients by apparent clinical risk: low risk (common benign conditions, geographic tongue, candidiasis, trauma), intermediate risk (lichenoid lesions) and high risk (white or red lesions or ulcers without apparent cause). Clinicians made the decision on which lesions to reassess in 3 weeks based on risk assessment and clinical judgment. Lesions of concern were seen by a community facilitator or referred to an oral medicine specialist.

Results

Of 2542 patients were screened, and 389 lesions were identified (15% of patients). 350 were determined to be low risk (90%), 19 intermediate risk (IR) (5%), and 20 high risk (HR) (5%). One hundred and sixty‐six (43%) patients were recalled for 3‐week reassessment: 90% of HR lesions, 63% of IR lesions (63%), and 39% of low‐risk lesions. Compliance to recall was high (92% of cases). Reassessment eliminated the referral of 99/166 (60%) of lesions that had resolved. six lesions were biopsied with three low‐grade dysplasias identified.

Conclusions

Three key decision points were tested: risk assessment, need for reassessment, and need for referral. A 3‐week reassessment appointment was invaluable to prevent the unnecessary referral due to confounders. There is a need for a well‐defined triage pathway to facilitate oral cancer screening and a methodical and consistent approach to opportunistic screening in the dental office.
Impact of dental caries and trauma on quality of life among 5‐ to 6‐year‐old children: perceptions of parents and children
Authors: Abanto Jenny , Tsakos Georgios , Paiva Saul Martins , Carvalho Thiago S. , Raggio Daniela P. , Bönecker Marcelo
Published: January 2014

Objective

To assess the impact of dental caries and traumatic dental injuries (TDI) on the oral health‐related quality of life (OHRQoL) of 5‐ to 6‐year‐olds according to both self‐ and parental reports.

Methods

A total of 335 pairs of parents and children who sought dental screening at the Dental School, University of São Paulo, completed the Scale of Oral Health Outcomes for 5‐year‐old children (SOHO‐5), which consists of a child self‐report and a parental proxy‐report version. Three calibrated examiners assessed the experience of caries according to primary teeth that were decayed, indicated for extraction due to caries, or filled (def‐t). TDI were classified into uncomplicated and complicated injuries. Poisson regression models were used to associate the different clinical and sociodemographic factors to the outcome.

Results

Overall, 74.6% of children reported an oral impact, and the corresponding estimate for parental reports was 70.5%. The mean (standard deviation) SOHO‐5 scores in child self‐report and parental versions were 3.32(3.22) and 5.18(6.28), respectively. In both versions, caries was associated with worse children's OHRQoL, for the total score and all SOHO‐5 items (P < 0.001). In contrast, TDI did not have a negative impact on children's OHRQoL, with the exception of two items of the parental version and one item of the child self‐report version. In the final multivariate adjusted models, there was a gradient in the association between caries experience and child's OHRQoL with worse SOHO‐5 score at each consecutive level with more severe caries experience, for both child and parental perceptions [RR (CI 95%) = 6.37 (4.71, 8.62) and 10.81 (7.65, 15.27)], respectively. A greater family income had a positive impact on the children's OHRQoL for child and parental versions [RR (CI 95%) = 0.68 (0.49, 0.94) and 0.70 (0.54, 0.90)], respectively.

Conclusions

Dental caries, but not TDI, is associated with worse OHRQoL of 5‐ to 6‐year‐old children in terms of perceptions of both children and their parents. Families with higher income report better OHRQoL at this age, independent of the presence of oral diseases.
An immune response study of oakmoss absolute and its constituents atranol and chloroatranol
Authors: Menné Bonefeld Charlotte , Nielsen Morten Milek , Gimenéz‐Arnau Elena , Lang Matthieu , Vennegaard Marie Torp , Geisler Carsten , Johansen Jeanne Duus , Lepoittevin Jean‐Pierre
Published: January 2014

Background

Atranol and chloroatranol are the main allergens of oakmoss absolute. However, the immune responses induced by these substances are poorly characterized.

Objectives

To characterize immune responses induced by atranol, chloroatranol and oakmoss absolute in mice.

Methods

Mice were sensitized and challenged with various concentrations of atranol, chloroatranol, and oakmoss absolute. The immune responses were analysed as B cell infiltration, T cell proliferation in the draining lymph nodes, and expression of interleukin (IL)‐18, IL‐1β and tumour necrosis factor‐α in skin. The cytotoxicity of atranol and chloroatranol against keratinocytes was determined.

Results

Sensitization experiments showed that atranol, chloroatranol and oakmoss induced sensitization when applied in high concentrations. Challenge experiments showed that even low concentrations of atranol and chloroatranol induced sensitization. In parallel, atranol and chloroatranol elicited challenge reactions following sensitization with oakmoss. The magnitude of the immune response to the three allergens increased in the following order: atranol, chloroatranol, and oakmoss. The expression of proinflammatory cytokines was induced by chloroatranol and oakmoss, but not by atranol. Chloroatranol was found to be more cytotoxic than atranol against keratinocytes.

Conclusions

Atranol and chloroatranol can elicit both sensitization and challenge reactions, but the mixture of allergens in oakmoss absolute is more potent than atranol and chloroatranol alone.
Exotic birds show lags in population growth
Authors: Aagaard Kevin , Lockwood Julie
Published: January 2014

Aim

A key aspect of the ecology and management of biological invasions is the prevalence and duration of lag phases in population growth. Here, we explore the occurrence of lag phases in exotic bird populations using theAudubonChristmasBirdCount database.

Location

HawaiianIsland archipelago.

Methods

We expand on the use of piecewise model fitting techniques to detect lags in exotic bird populations onHawaii. We searched for explanations as to the occurrence of these lags using five possible mechanisms (body size, niche breadth, propagule pressure, length of record and lag phase growth rate).

Results

We found evidence of lag phases for 14 of 17 species we evaluated (range: 10–38 years, mean using observed data = 16 ± 12), and we discovered very rapid growth to maximum abundance following the end of the lag phase (mean using observed data = 8 ± 6 years). We found no evidence for any association between the possible mechanisms influencing the occurrence and duration of the lag phases.

Main conclusions

Our results are the first to rigorously quantify lags in exotic animal populations; most existing evidence comes from plants. We show that lags are as common in birds as in plants, although we provide preliminary evidence that the duration of lags in birds is shorter than in plants. We highlight the need for continued efforts to elucidate lag phase occurrence and duration in biological invasions, and we demonstrate the expanded utility of piecewise model fitting approaches to quantify these lags using count data.
Approaching low liver iron burden in chelated patients with non‐transfusion‐dependent thalassemia: the safety profile of deferasirox
Authors: Taher Ali T. , Porter John B. , Viprakasit Vip , Kattamis Antonis , Chuncharunee Suporn , Sutcharitchan Pranee , Siritanaratkul Noppadol , Origa Raffaella , Karakas Zeynep , Habr Dany , Zhu Zewen , Cappellini M. Domenica
Published: January 2014

Objective

Patients with non‐transfusion‐dependent thalassemia (NTDT) often develop iron overload and related complications, and may require iron chelation. However, the risk of over‐chelation emerges as patients reach low, near‐normal body iron levels and dose adjustments may be needed. In the THALASSA study, the threshold for chelation interruption was LIC <3 mg Fe/g dw (LIC<3); 24 patients receiving deferasirox for up to 2 yr reached this target. A post hoc analysis was performed to characterize the safety profile of deferasirox as these patients approached LIC<3.

Methods

THALASSA was a randomized, double‐blind, placebo‐controlled study of two deferasirox regimens (5 and 10 mg/kg/d) versus placebo in patients with NTDT. Patients randomized to deferasirox or placebo in the core could enter a 1‐yr extension, with all patients receiving deferasirox (extension starting doses based on LIC at end‐of‐core and prior chelation response). The deferasirox safety profile was assessed between baseline and 6 months before reaching LIC<3 (Period 1), and the 6 months immediately before achieving LIC<3 (Period 2).

Results

Mean ± SD deferasirox treatment duration up to reaching LIC<3 was 476 ± 207 d, and deferasirox dose was 9.7 ± 3.0 mg/kg/d. The exposure‐adjusted AE incidence regardless of causality was similar in periods 1 (1.026) and 2 (1.012). There were no clinically relevant differences in renal and hepatic laboratory parameters measured close to the time of LIC<3 compared with measurements near the previous LIC assessment.

Conclusions

The deferasirox safety profile remained consistent as patients approached the chelation interruption target, indicating that, with appropriate monitoring and dose adjustments in relation to iron load, low iron burdens may be reached with deferasirox with minimal risk of over‐chelation.
Genetics of Parkinson's disease: alpha‐synuclein and other insights from Greece
Authors: Proukakis C.
Published: January 2014

Click here to view the accompanying paper in this issue.
Temporal trends in epilepsy surgery
Authors: Neligan A.
Published: January 2014

Click here to view the accompanying paper in this issue.
Role of a histamine 4 receptor as an anti‐inflammatory target in carrageenan‐induced pleurisy in mice
Authors: Ahmad Sheikh Fayaz , Zoheir Khairy M. A. , Abdel‐Hamied Hala E. , Alrashidi Ibrahim , Attia Sabry M. , Bakheet Saleh A. , Ashour Abdelkader E. , Abd‐Allah Adel R. A.
Published: January 2014

The histamine 4 receptor (H4R) is expressed primarily on cells involved in inflammation and immune responses. Despite much research into inflammatory diseases, no drugs with favourable safety profiles are yet available for their treatment. The aim of the present study was to determine the potential anti‐inflammatory effect of 4‐methylhistamine (4‐MeH) or JNJ77777120 (JNJ) and to explore the role of H4R in a mouse model of carrageenan (Cg) ‐induced pleurisy. A single dose of 4‐MeH or JNJ (30 mg/kg) was administered intraperitoneally 1 hr before Cg administration. The results illustrate that both the numbers of CD4+, CD25+, CD4+ CD25+, GITR+, GITR+ IL‐17A+‐expressing T cells and the levels of T helper type 1 (Th1)/Th17 cytokines were markedly increased in both the Cg‐treated and 4‐MeH‐treated groups, whereas the cytokines produced by Th2 cells were significantly decreased in the same groups. However, JNJ treatment significantly decreased both the number of T‐cell subsets and GITR+, GITR+ IL‐17A+‐expressing T cells, and the production of Th1/Th17 cytokines. Further, JNJ up‐regulated the expression of the Th2 cytokines. RT‐PCR analysis revealed an increased expression of interleukin‐1β, tumour necrosis factor‐α, monocyte chemoattractant protein‐1 and intercellular adhesion molecule‐1 in the Cg‐treated and 4‐MeH‐treated groups, which was reduced by treatment with JNJ in lung tissues. Moreover, histological examinations revealed anti‐inflammatory effects of JNJ, whereas 4‐MeH worsened Cg‐induced inflammation. In conclusion, the results of the present work clearly indicate that JNJ possesses important anti‐inflammatory properties that are increased in 4‐MeH‐treated mice, suggesting that H4R are involved in pleurisy and that JNJ has an anti‐inflammatory effect in associated disease conditions.
Pericellular oxygen monitoring with integrated sensor chips for reproducible cell culture experiments
Authors: Kieninger J. , Aravindalochanan K. , Sandvik J. A. , Pettersen E. O. , Urban G. A.
Published: January 2014

Objectives

Here we present an application, in two tumour cell lines, based on the Sensing Cell Culture Flask system as a cell culture monitoring tool for pericellular oxygen sensing.

Materials and methods

T‐47D (human breast cancer) and T98G (human brain cancer) cells were cultured either in atmospheric air or in a glove‐box set at 4% oxygen, in both cases with 5% CO2 in the gas phase. Pericellular oxygen tension was measured with the help of an integrated sensor chip comprising oxygen sensor arrays.

Results

Obtained results illustrate variation of pericellular oxygen tension in attached cells covered by stagnant medium. Independent of incubation conditions, low pericellular oxygen concentration levels, usually associated with hypoxia, were found in dense cell cultures.

Conclusions

Respiration alone brought pericellular oxygen concentration down to levels which could activate hypoxia‐sensing regulatory processes in cultures believed to be aerobic. Cells in culture believed to experience conditions of mild hypoxia may, in reality, experience severe hypoxia. This would lead to incorrect assumptions and suggests that pericellular oxygen concentration readings are of great importance to obtain reproducible results when dealing with hypoxic and normoxic (aerobic) incubation conditions. The Sensing Cell Culture Flask system allows continuous monitoring of pericellular oxygen concentration with outstanding long‐term stability and no need for recalibration during cell culture experiments. The sensor is integrated into the flask bottom, thus in direct contact with attached cells. No additional equipment needs to be inserted into the flask during culturing. Transparency of the electrochemical sensor chip allows optical inspection of cells attached on top of the sensor.
Assessment and Treatment of Challenging Behaviour for Individuals with Intellectual Disability: A Research Review
Authors: Lloyd Blair P. , Kennedy Craig H.
Published: January 2014

Background

Challenging behaviour is frequently associated with the presence of intellectual disability. If not effectively treated, chronic challenging behaviour can negatively impact a variety of quality of life outcomes for individuals with intellectual disability.

Methods and Results

We review the current status of research relating to the assessment and treatment of challenging behaviour for people with intellectual disability. We briefly review the history of interventions for challenging behaviour that led to the development of function‐based approaches widely in use today. We then discuss the various operant functions of challenging behaviour, functional behaviour assessment technologies and reinforcement‐based interventions.

Conclusions

We conclude with a discussion of future directions that include models of prevention, ecological validity of assessment procedures and the widespread use of comprehensive behavioural support programmes.
Dissection of additive genetic variability for quantitative traits in chickens using SNP markers
Authors: Abdollahi‐Arpanahi R. , Pakdel A. , Nejati‐Javaremi A. , Moradi Shahrbabak M. , Morota G. , Valente B.D. , Kranis A. , Rosa G.J.M. , Gianola D.
Published: January 2014

The aim of this study was to separate marked additive genetic variability for three quantitative traits in chickens into components associated with classes of minor allele frequency (MAF), individual chromosomes and marker density using the genomewide complex trait analysis (GCTA) approach. Data were from 1351 chickens measured for body weight (BW), ultrasound of breast muscle (BM) and hen house egg production (HHP), each bird with 354 364 SNP genotypes. Estimates of variance components show that SNPs on commercially available genotyping chips marked a large amount of genetic variability for all three traits. The estimated proportion of total variation tagged by all autosomal SNPs was 0.30 (SE 0.04) for BW, 0.33 (SE 0.04) for BM, and 0.19 (SE 0.05) for HHP. We found that a substantial proportion of this variation was explained by low frequency variants (MAF <0.20) for BW and BM, and variants with MAF 0.10–0.30 for HHP. The marked genetic variance explained by each chromosome was linearly related to its length (R2 = 0.60) for BW and BM. However, for HHP, there was no linear relationship between estimates of variance and length of the chromosome (R2 = 0.01). Our results suggest that the contribution of SNPs to marked additive genetic variability is dependent on the allele frequency spectrum. For the sample of birds analysed, it was found that increasing marker density beyond 100K SNPs did not capture additional additive genetic variance.
Engineering of pre‐vascularized urethral patch with muscle flaps and hypoxia‐activated hUCMSCs improves its therapeutic outcome
Authors: Sun Dongchong , Yang Yong , Wei Zhitao , Xu Yong , Zhang Xu , Hong Baofa
Published: January 2014

Tissue engineering has brought new hopes for urethral reconstruction. However, the absence of pre‐vascularization and the subsequent degradation of materials often lead to the failure of in vivo application. In this study, with the assistance of hypoxia‐activated human umbilical cord mesenchymal stem cells (hUCMSCs), pedicled muscle flaps were used as materials and pre‐incubated in ventral penile subcutaneous cavity of rabbit for 3 weeks to prepare a pre‐vascularized urethral construct. We found that small vessels and muscle fibres were scattered in the construct after 3 weeks' pre‐incubation. The construct presented a fibrous reticular structure, which was similar to that of the corpus spongiosum under microscope examination. The produced constructs were then used as a patch graft for reconstruction of the defective rabbit urethra (experimental group), natural muscular patch was used as control (control group). Twelve weeks after the reconstructive surgery, urethrography and urethroscope inspections showed wide calibres of the reconstructed urethra in the experimental group. Histopathological studies revealed that fibrous connective tissues and abundant muscle fibres constituted the main body of the patch‐grafted urethra. In contrast, in the control group, only adipose tissue was found in the stenosis‐reconstructed urethra, replacing the originally grafted muscular tissue. To our knowledge, this is the first report that successfully constructed a pre‐vascularized urethral construct by using hypoxia‐activated hUCMSC and pedicled muscle flaps. More importantly, the pre‐vascularized construct showed a good performance in urethral reconstruction when applied in vivo. The study provided a novel strategy for tissue engineering of pre‐vascularized urethral construct for the defective urethra, representing a further advancement in urethral reconstruction.
Skin‐Tissue‐sparing Excision with Electrosurgical Peeling (STEEP): a surgical treatment option for severe hidradenitis suppurativa Hurley stage II/III
Authors: Blok J.L. , Spoo J.R. , Leeman F.W.J. , Jonkman M.F. , Horváth B.
Published: January 2014

Background

Surgery is the only curative treatment for removal of the persistent sinus tracts in the skin that are characteristic of severe hidradenitis suppurativa (HS). Complete resection of the affected tissue by wide excision is currently regarded as the preferred surgical technique in these cases. However, relatively large amounts of healthy tissue are removed with this method and suitable skin‐tissue‐saving techniques aiming at creating less‐extensive surgical defects are therefore needed in severe HS.

Method

We describe a skin‐tissue‐saving surgical technique for HS Hurley stage II–III disease: the Skin‐Tissue‐sparing Excision with Electrosurgical Peeling (STEEP) procedure.

Discussion

In contrast to wide excisions that generally reach into the deep subcutaneous fat, the fat is maximally spared with the STEEP procedure by performing successive tangential excisions of lesional tissue until the epithelialized bottom of the sinus tracts has been reached. From here, secondary intention healing can occur. In addition, fibrotic tissue is completely removed in the same manner as this also serves as a source of recurrence. This tissue‐sparing technique results in low recurrence rates, high patient satisfaction with relatively short healing times and favourable cosmetic outcomes without contractures.
Development of a rectal sexually transmitted infection – HIV coinfection model utilizing Chlamydia trachomatis and SHIVSF162p3
Authors: Henning Tara , Butler Katherine , Mitchell James , Ellis Shanon , Deyounks Frank , Farshy Carol , Phillips Christi , Papp John , Patton Dorothy , Caldwell Harlan , Sturdevant Gail , McNicholl Janet , Kersh Ellen
Published: January 2014

Background

Rectal sexually transmitted infections (STIs) may increase HIV susceptibility in men who have sex with men (MSM), and Chlamydia trachomatis is prevalent among HIV‐positive MSM. To study STIs and HIV infection in MSM, we first evaluated whether cynomolgus macaques can sustain both C. trachomatis and SHIVSF162p3 infections.

Methods

Four SHIVSF162p3‐positive male cynomolgus macaques were used (n = 3 rectally inoculated with 106 IFU; n = 1 control). Systemic and rectal SHIV RNA levels and cytokines were measured by real‐time PCR and Luminex assays, respectively.

Results

Macaques were successfully Chlamydia infected. Rectal SHIV shedding (P = 0.02 χ2) and levels of G‐CSF, IL‐1ra, IL‐6, IL‐8, IFN‐γ, and TNF‐α (P ≤ 0.01, Mann–Whitney) in rectal secretions increased following infection.

Conclusions

These pilot data successfully demonstrate rectal C. trachomatis–SHIV coinfection in cynomolgus macaques and suggest the feasibility of a rectal C. trachomatis model for SHIV susceptibility and biomedical prevention studies in the context of rectal STIs.
The oxidized form of vitamin C, dehydroascorbic acid, regulates neuronal energy metabolism
Authors: Cisternas Pedro , Silva‐Alvarez Carmen , Martínez Fernando , Fernandez Emilio , Ferrada Luciano , Oyarce Karina , Salazar Katterine , Bolaños Juan P. , Nualart Francisco
Published: January 2014

Vitamin C is an essential factor for neuronal function and survival, existing in two redox states, ascorbic acid (AA), and its oxidized form, dehydroascorbic acid (DHA). Here, we show uptake of both AA and DHA by primary cultures of rat brain cortical neurons. Moreover, we show that most intracellular AA was rapidly oxidized to DHA. Intracellular DHA induced a rapid and dramatic decrease in reduced glutathione that was immediately followed by a spontaneous recovery. This transient decrease in glutathione oxidation was preceded by an increase in the rate of glucose oxidation through the pentose phosphate pathway (PPP), and a concomitant decrease in glucose oxidation through glycolysis. DHA stimulated the activity of glucose‐6‐phosphate dehydrogenase, the rate‐limiting enzyme of the PPP. Furthermore, we found that DHA stimulated the rate of lactate uptake by neurons in a time‐ and dose‐dependent manner. Thus, DHA is a novel modulator of neuronal energy metabolism by facilitating the utilization of glucose through the PPP for antioxidant purposes.

image

We proposed that the ascorbic acid (AA) taken up by neurons is rapidly oxidized to dehydroascorbic acid (DHA), which inhibits glycolysis and activates the pentose phosphate pathway (PPP), consequently producing NADPH, a critical antioxidant in the recycling of oxidized glutathione (GSSG). In these metabolic conditions, neurons increase lactate uptake, probably using it as an energy source. This data supported the idea that DHA could play a critical role in the modulation of energy metabolism in neurons.
Characterisation of the cytokine milieu associated with the up‐regulation of IL‐6 and suppressor of cytokine 3 in chronic hepatitis C treatment non‐responders
Authors: Martinez Danica , Palmer Clovis , Simar David , Cameron Barbara A. , Nguyen Nam , Aggarwal Vipul , Lloyd Andrew R. , Zekry Amany
Published: January 2014

Background & Aims

In chronic hepatitis C virus infection (CHC), expression of suppressor of cytokine signalling‐3 (SOCS3) has been shown to be associated with obesity and non‐response to antiviral therapy. In this study, we aimed to determine the effect of SOCS3 induction on the cytokine response in patients receiving Pegylated interferon (PegIFN) and ribavirin (RBV) therapy.

Methods

Peripheral blood mononuclear cells (PBMC) collected at baseline and at 12 weeks from CHC patients receiving PegIFN/RBV therapy were examined for mRNA and protein SOCS3 expression. Immunological assays were employed to examine cytokine production.

Results

There was increased expression of SOCS3 in PBMC of non‐responders at week 12 of therapy, when compared to treatment responders (P = 0.0001). The expression of SOCS3 correlated with body mass index (BMI) (r = 0.54; P = 0.01). Patients with low SOCS3 expression at week 12 of therapy had lower HCV‐specific IFN‐γ production in enzyme‐linked immunosorbent spot (ELISpot) assays (P = 0.01), and reduced ex‐vivo production of the anti‐HCV effector cytokines interleukin (IL)‐2 and tumour necrosis factor (TNF)‐α(P = 0.01 and P = 0.04 respectively). Analysis of serum cytokine levels revealed higher levels of IL‐6 at week 12 in the high SOCS3 expression group (P = 0.02) while IL‐6 levels correlated with SOCS3 expression in the entire cohort (P = 0.04). Ex‐vivo studies confirmed that IL‐6 induced SOCS3, and neutralisation of IL‐6 reduced levels of SOCS3.

Conclusion

In subjects with increased BMI and non‐response to antiviral therapy, the IL‐6/SOCS3 axis appears to play a crucial role in altering the anti‐HCV‐cytokine response associated with antiviral therapy.
Treatments to slow progression of autosomal dominant polycystic kidney disease: systematic review and meta‐analysis of randomized trials
Authors: Myint Thida M , Rangan Gopi K , Webster Angela C
Published: January 2014

Aim

Autosomal dominant polycystic kidney disease (ADPKD) is a monogenetic disorder that leads to kidney failure. Our aim was to undertake a meta‐analysis of randomized trials of interventions that have been hypothesized to reduce the progression of total kidney volume (TKV) and renal function in ADPKD.

Methods

Relevant trials were identified, and outcomes were: change in TKV, total cyst volume (TCV), renal function and adverse events. Meta‐analysis used random effects, with results expressed as mean difference and risk ratio both with 95% confidence intervals (CI).

Results

Eleven trials (2262 patients) were included. Compared with placebo, Target of Rapamycin complex 1 (TORC1) inhibitors (5 trials, n = 619), showed no significant change in TKV (P = 0.21), TCV (P = 0.06) or eGFR (P = 0.22). Somatostatin analogues (3 trials, n = 157) reduced TKV by 9% (95% CI −10.33 to −7.58%) but did not alter eGFR. The vasopressin receptor antagonist (n = 1455) attenuated TKV increase to 3%/year (95% CI −3.48 to −2.52) and slowed kidney function decline over a 3‐year period. A single trial (n = 41) of eicosapentaenoic acid did not alter the progression of either TKV (P = 0.9) or renal dysfunction (P = 0.78). Adverse events were significant for interventions in all trials compared with placebo.

Conclusion

These data suggest that somatostatin analogues and vasopressin receptor antagonists attenuate TKV increase. The neutral effects of TORC1 inhibitors on TKV could be true, or due to heterogeneity in study population, drug efficacy and follow‐up duration. In the future, further well‐designed and powered trials of longer duration using new biomarkers or therapeutic agents with better tolerance are required.
Strategic patent analysis in plant biotechnology: terpenoid indole alkaloid metabolic engineering as a case study
Authors: Miralpeix Bruna , Sabalza Maite , Twyman Richard M. , Capell Teresa , Christou Paul
Published: January 2014

The do‐it‐yourself patent search is a useful alternative to professional patent analysis particularly in the context of publicly funded projects where funds for IP activities may be limited. As a case study, we analysed patents related to the engineering of terpenoid indole alkaloid (TIA) metabolism in plants. We developed a focused search strategy to remove redundancy and reduce the workload without missing important and relevant patents. This resulted in the identification of approximately 50 key patents associated with TIA metabolic engineering in plants, which could form the basis of a more detailed freedom‐to‐operate analysis. The structural elements of this search strategy could easily be transferred to other contexts, making it a useful generic model for publicly funded research projects.
Regulatory options for genetically modified crops in India
Authors: Choudhary Bhagirath , Gheysen Godelieve , Buysse Jeroen , van der Meer Piet , Burssens Sylvia
Published: January 2014

The introduction of semi‐dwarfing, high‐yielding and nutrients‐responsive crop varieties in the 1960s and 1970s alleviated the suffering of low crop yield, food shortages and epidemics of famine in India and other parts of the Asian continent. Two semi‐dwarfing genes, Rht in wheat and Sd‐1 in rice heralded the green revolution for which Dr. Norman Borlaug was awarded the Nobel Peace Prize in 1970. In contrast, the revolutionary new genetics of crop improvement shamble over formidable obstacles of regulatory delays, political interferences and public misconceptions. India benefited immensely from the green revolution and is now grappling to deal with the nuances of GM crops. The development of GM mustard discontinued prematurely in 2001 and insect‐resistant Bt cotton varieties were successfully approved for commercial cultivation in 2002 in an evolving nature of regulatory system. However, the moratorium on Bt brinjal by MOEF in 2010 meant a considerable detour from an objective, science‐based, rigorous institutional process of regulatory approval to a more subjective, nonscience‐driven, political decision‐making process. This study examines what ails the regulatory system of GM crops in India and the steps that led to the regulatory logjam. Responding to the growing challenges and impediments of existing biosafety regulation, it suggests options that are critical for GM crops to take roots for a multiplier harvest.
Photodecomposition of Chloroform Catalyzed by Unmodified MCM‐41 Mesoporous Silica
Authors: Peña Laura A. , Chan Alissa M. , Cohen Larissa R. , Hou Karen , Harvey Brent M. , Hoggard Patrick E.
Published: January 2014

Unactivated MCM‐41 mesoporous silica catalyzes the photodecomposition of chloroform to phosgene and hydrogen chloride under near‐UV (λ > 360 nm) irradiation. The rate of photodecomposition increases toward an asymptotic limit as the O2 partial pressure is increased. Deuterochloroform does not decompose under the same experimental conditions. Low concentrations of both cyclohexane and ethanol quench the photodecomposition, whereas water, up to its solubility limit, does not. Dissolved tetraalkylammonium salts suppress photodecomposition. The data are consistent with a mechanism in which light absorption by an SiO2 defect yields an electron‐deficient oxygen atom, which then abstracts hydrogen from chloroform. The resulting CCl3 radicals react with oxygen to form a peroxy radical that decomposes, eventually yielding phosgene and hydrogen chloride.
miR444a has multiple functions in the rice nitrate‐signaling pathway
Authors: Yan Yongsheng , Wang Huacai , Hamera Sadia , Chen Xiaoying , Fang Rongxiang
Published: January 2014

Nitrate () is a key signaling molecule in plant metabolism and development, in addition to its role as a nutrient. It has been shown previously in Arabidopsis that ANR1, a MADS‐box transcription factor, is a major component in the ‐signaling pathway that triggers lateral root growth and that miR444, which is specific to monocots, targets four genes that are homologous to ANR1 in rice. Here, we show that miR444a plays multiple roles in the rice ‐signaling pathway – not only in root development, but also involving nitrate accumulation and even Pi‐starvation responses. miR444a overexpression resulted in reduced rice lateral root elongation, but promoted rice primary and adventitious root growth, in a nitrate‐dependent manner. In addition, overexpression of miR444a improved nitrate accumulation and expression of nitrate transporter genes under high nitrate concentration conditions, but reduced the remobilization of nitrate from old leaves to young leaves thus affecting the plant's ability to adapt to nitrogen‐limitating conditions. Intriguingly, we found that Pi starvation strongly induced miR444 accumulation in rice roots and that overexpression of miR444a altered Pi‐starvation‐induced root architecture and enhanced Pi accumulation and expression of three Pi transporter genes. We further provide evidence that miR444a is involved in the interaction between the ‐signaling and Pi‐signaling pathways in rice. Taken together, our observations demonstrated that miR444a plays multiple roles in the rice ‐signaling pathway in nitrate‐dependent root growth, nitrate accumulation and phosphate‐starvation responses.
Auxin biosynthetic gene TAR2 is involved in low nitrogen‐mediated reprogramming of root architecture in Arabidopsis
Authors: Ma Wenying , Li Jingjuan , Qu Baoyuan , He Xue , Zhao Xueqiang , Li Bin , Fu Xiangdong , Tong Yiping
Published: January 2014

In plants, the plasticity of root architecture in response to nitrogen availability largely determines nitrogen acquisition efficiency. One poorly understood root growth response to low nitrogen availability is an observed increase in the number and length of lateral roots (LRs). Here, we show that low nitrogen‐induced Arabidopsis LR growth depends on the function of the auxin biosynthesis gene TAR2 (tryptophan aminotransferase related 2). TAR2 was expressed in the pericycle and the vasculature of the mature root zone near the root tip, and was induced under low nitrogen conditions. In wild type plants, low nitrogen stimulated auxin accumulation in the non‐emerged LR primordia with more than three cell layers and LR emergence. Conversely, these low nitrogen‐mediated auxin accumulation and root growth responses were impaired in the tar2‐c null mutant. Overexpression of TAR2 increased LR numbers under both high and low nitrogen conditions. Our results suggested that TAR2 is required for reprogramming root architecture in response to low nitrogen conditions. This finding suggests a new strategy for improving nitrogen use efficiency through the engineering of TAR2 expression in roots.
Cutaneous involvement in canine leishmaniosis due to Leishmania infantum (syn. L.chagasi)
Authors: Saridomichelakis Manolis N. , Koutinas Alexander F.
Published: January 2014

Background

Canine leishmaniosis, a zoonotic infectious disease caused by Leishmania infantum (syn. L. chagasi), is fairly common in endemic areas, and skin lesions are the most frequent clinical manifestation. Despite the large volume of relevant scientific information, there is a relative paucity of up‐to‐date review articles on the cutaneous manifestations of the disease.

Hypothesis/Objectives

This review provides current information on the macroscopic and histological skin lesions of dogs with leishmaniosis and comments on their pathogenesis and definitive diagnosis.

Methods

Published articles have been thoroughly reviewed and the retrieved information has been used and supplemented as appropriate with the authors' clinical experience.

Results

The main clinicopathological presentations of canine leishmaniosis are exfoliative, ulcerative, nodular, sterile pustular and papular dermatitis and nodules at the site of parasite inoculation. Histopathology is usually dominated by mononuclear inflammatory infiltrates; immunohistochemical findings are variable, and Leishmania amastigotes are present in both diseased and normal‐looking skin of dogs with leishmaniosis. Definitive diagnosis of the skin lesions in a dog with leishmaniosis is based on their macroscopic appearance, exclusion of main differentials, histopathology, demonstration of the parasite in the skin and complete response to antileishmanial treatment.

Conclusions and clinical importance

Canine leishmaniosis due to L. infantum is characterized by diverse cutaneous manifestations that may reflect different host–parasite relationships. Furthermore, different types of skin lesions may occur, in various combinations, in the same dog. The definitive diagnosis of these lesions is based on clinical and laboratory examinations and on the response to antileishmanial treatment.