bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecological Importance of Insects in Selenium Biogenic Cycling
Authors: Golubkina Nadezhda , Sheshnitsan Sergey , Kapitalchuk Marina
Published: February 2014

Selenium is an essential trace element for animal and human beings. Despite the importance of insects in most ecosystems and their significant contribution to the biological cycling of trace elements due to high abundance, population productivity, and diverse ecosystem functions, surprisingly little information is available on selenium bioaccumulation by these arthropods. This review considers selenium essentiality and toxicity to insects as well as insects’ contribution to selenium trophic transfer through the food chains. Data on Se accumulation by insects of the Dniester River Valley with no anthropogenic Se loading reveal typically low Se content in necrophagous insects compared to predators and herbivores and seasonal variations in Se accumulation.
Cutaneous Plasmacytosis with Perineural Involvement
Authors: Brezinski Elizabeth A. , Fung Maxwell A. , Fazel Nasim
Published: February 2014

Importance. Cutaneous and systemic plasmacytosis are rare conditions of unknown etiology with characteristic red-brown skin lesions and a mature polyclonal plasma cell infiltrate within the dermis. Perineural plasma cell infiltrates may be a histologic clue to the diagnosis of cutaneous plasmacytosis.Observations. Our patient had a five-year history of persistent reddish-brown plaques on the neck and trunk without systemic symptoms. Histologic examination showed dermal perivascular and perineural plasma cells with excess lambda light chain expression. Due to decreased quality of life caused by his skin lesions, he was placed on a chemotherapeutic regimen with bortezomib.Conclusions and Relevance. The patient was diagnosed with cutaneous plasmacytosis based on classic histopathology results with a recently characterized pattern of perineural involvement. Bortezomib therapy was initiated to manage his skin eruption, which has not been previously described as a treatment for this chronic condition.
Global Dynamics of a Mathematical Model on Smoking
Authors: Alkhudhari Zainab , Al-Sheikh Sarah , Al-Tuwairqi Salma
Published: February 2014

We derive and analyze a mathematical model of smoking in which the population is divided into four classes: potential smokers, smokers, temporary
quitters, and permanent quitters. In this model we study the effect of smokers on
temporary quitters. Two equilibria of the model are found: one of them is the
smoking-free equilibrium and the other corresponds to the presence of smoking. We
examine the local and global stability of both equilibria and we support our results
by using numerical simulations.
Human Lung Mast Cell Products Regulate Airway Smooth Muscle CXCL10 Levels
Authors: Alkhouri H. , Cha V. , Tong K. , Moir L. M. , Armour C. L. , Hughes J. M.
Published: February 2014

In asthma, the airway smooth muscle (ASM) produces CXCL10 which may attract CXCR3+ mast/T cells to it. Our aim was to investigate the effects of mast cell products on ASM cell CXCL10 production. ASM cells from people with and without asthma were stimulated with IL-1β, TNF-α, and/or IFNγ and treated with histamine (1–100 μM) ± chlorpheniramine (H1R antagonist; 1 μM) or ranitidine (H2R antagonist; 50 μM) or tryptase (1 nM) ± leupeptin (serine protease inhibitor; 50 μM), heat-inactivated tryptase, or vehicle for 4 h or 24 h. Human lung mast cells (MC) were isolated and activated with IgE/anti-IgE and supernatants were collected after 2 h or 24 h. The supernatants were added to ASM cells for 48 h and ASM cell CXCL10 production detected using ELISA (protein) and real-time PCR (mRNA). Histamine reduced IL-1β/TNF-α-induced CXCL10 protein, but not mRNA, levels independent of H1 and H2 receptor activation, whereas tryptase and MC 2 h supernatants reduced all cytokine-induced CXCL10. Tryptase also reduced CXCL10 levels in a cell-free system. Leupeptin inhibited the effects of tryptase and MC 2 h supernatants. MC 24 h supernatants contained TNF-α and amplified IFNγ-induced ASM cell CXCL10 production. This is the first evidence that MC can regulate ASM cell CXCL10 production and its degradation. Thus MC may regulate airway myositis in asthma.
Evaluation and Treatment of Perioperative Corneal Abrasions
Authors: Segal Kira L. , Fleischut Peter M. , Kim Charles , Levine Ben , Faggiani Susan L. , Banerjee Samprit , Gadalla Farida , Lelli Gary J.
Published: February 2014

Purpose.To evaluate perioperative risk factors for corneal abrasion (CA) and to determine current care for perioperative CA in a tertiary care setting.Methods.Hospital-based, cross-sectional study. In Operating Room and Post-Anesthesia Care Units patients, a comparison of cases and controls was evaluated to elucidate risk factors, time to treatment, and most common treatments prescribed for corneal abrasions.Results.86 cases of corneal abrasion and 89 controls were identified from the 78,542 surgical procedures performed over 2 years. Statistically significant risk factors were age (P=0.0037), general anesthesia (P<0.001), greater average estimated blood loss (P<0.001), eyes taped during surgery (P<0.001), prone position (P<0.001), trendelenburg position (P<0.001), and supplemental oxygen en route to and in the Post-Anesthesia Care Units (P<0.001). Average time to complaint was 129 minutes. 94% of cases had an inpatient ophthalmology consult, with an average time to consult of 164 minutes. The most common treatment was artificial tears alone (40%), followed by combination treatment of antibiotic ointment and artificial tears (35.3%).Conclusions.Trendelenburg positioning is a novel risk factor for CA. Diagnosis and treatment of perioperative corneal abrasions by an ophthalmologist typically require three hours in the tertiary care setting.
A System of Differential Set-Valued Variational Inequalities in Finite Dimensional Spaces
Authors: Li Wei , Wang Xing , Huang Nan-Jing
Published: February 2014

A system of differential set-valued variational inequalities is introduced and studied in finite dimensional Euclidean spaces. An existence theorem of weak solutions for the system of differential set-valued variational inequalities in the sense of Carathéodory is proved under some suitable conditions. Furthermore, a convergence result on Euler time-dependent procedure for solving the system of differential set-valued variational inequalities is also given.
Glucagon-Like Peptide-1 Secreting Cell Function as well as Production of Inflammatory Reactive Oxygen Species Is Differently Regulated by Glycated Serum and High Levels of Glucose
Authors: Puddu Alessandra , Sanguineti Roberta , Montecucco Fabrizio , Viviani Giorgio L.
Published: February 2014

Glucagon-like peptide-1 (GLP-1), an intestinal hormone contributing to glucose homeostasis, is synthesized by proglucagon and secreted from intestinal neuroendocrine cells in response to nutrients. GLP-1 secretion is impaired in type 2 diabetes patients. Here, we aimed at investigating whether diabetic toxic products (glycated serum (GS) or high levels of glucose (HG)) may affect viability, function, and insulin sensitivity of the GLP-1 secreting cell line GLUTag. Cells were cultured for 5 days in presence or absence of different dilutions of GS or HG. GS and HG (alone or in combination) increased reactive oxygen species (ROS) production and upregulated proglucagon mRNA expression as compared to control medium. Only HG increased total production and release of active GLP-1, while GS alone abrogated secretion of active GLP-1. HG-mediated effects were associated with the increased cell content of the prohormone convertase 1/3 (PC 1/3), while GS alone downregulated this enzyme. HG upregulated Glucokinase (GK) and downregulated SYNTHAXIN-1. GS abrogated SYNTHAXIN-1 and SNAP-25. Finally, high doses of GS alone or in combination with HG reduced insulin-mediated IRS-1 phosphorylation. In conclusion, we showed that GS and HG might regulate different pathways of GLP-1 production in diabetes, directly altering the function of neuroendocrine cells secreting this hormone.
Molecular Dynamics Simulation of Solidification of Pd-Ni Clusters with Different Nickel Content
Authors: Gang Chen , Peng Zhang , Hongwei Liu
Published: February 2014

Molecular dynamics simulation has been performed for investigating the glass transition of Pd-Ni alloy nanoparticles in the solidification process. The results showed that the Pd-Ni nanoparticles with composition far from pure metal should form amorphous structure more easily, which is in accordance with the results of the thermodynamic calculation. There are some regular and distorted fivefold symmetry in the amorphous Pd-Ni alloy nanoparticles. The nanoclusters with bigger difference value between formation enthalpies of solutions and glasses will transform to glass more easily than the other Pd-Ni alloy nanoclusters.
Clinical and Contrast-Enhanced Ultrasound Echography Outcomes in Psoriatic Arthritis Patients after One Year of Continuous Therapy with Anti-TNF Drugs
Authors: Bonifati Claudio , Elia Fulvia , Graceffa Dario , Ceralli Fabrizio , Maiani Elisa , De Mutiis Carlo , Solivetti Francesco M.
Published: February 2014

Background. We wanted to verify retrospectively the proportion of patients with psoriatic arthritis who were in remission after 1 year of continuous therapy with either etanercept or adalimumab. Remission was defined as the absence of both clinical and contrast-enhanced ultrasound (CEUS) findings suggestive of joint inflammation. Patients and Methods. The data of twenty-five patients with psoriatic arthritis were available for the clinical and CEUS evaluations before and after 1 year of continuous therapy with etanercept or adalimumab. The count of swollen (ACR66), tender (ACR68), and active inflamed joints (AJC) was used to measure the severity of joint involvement. PASI was used to score the severity of psoriasis. HAQ, DLQI, VAS pain, and VAS itching were administered to each patient before starting therapy and every 3 months, up to 1 year. Results. Eight (32%) out of twenty-five patients were in remission after 1 year of therapy with etanercept or adalimumab. A significant reduction of all clinical variables analysed was seen during the course of therapy. Conclusion. Although a significant proportion of patients achieved remission of arthritis after 1 year of effective anti-TNF therapy, the majority of them continued to have either clinical or CEUS findings suggestive of persistence of joint inflammation.
Molecular and Microscopic-Based Characterization ofPlasmodiumspp. in Fars and Hormozgan Provinces, South of Iran
Authors: Mohammadzadeh Tahereh , Hatam Gholamreza , Kalantari Mohsen , Sarkari Bahador , Motazedian Mohammad Hosein , Sadjjadi Seyed Mahmoud , Safari Reza
Published: February 2014

Despite malaria control programs in recent years, malaria transmission has not been eliminated in Iran. Molecular techniques including PCR, which has proved more sensitive and specific than microscopic examination methods, help to detect infection in low levels of parasitemia and mixed infections. Main our objectives were setting up nested PCR for detection of malaria and evaluating PCR based on plasmodia DNA from blood smears in Fars province, the comparison of this method with traditional microscopy and also evaluate the data in comparison with its neighboring province, Hormozgan. A total of 149 malaria positive samples including 116, 19, and 14 samples from Shiraz, Jask, and Lengeh ports were utilized in this study, respectively. Blood slides were prepared for microscopic observation. DNA from thin smears was extracted and nested PCR was analyzed using rPLU5 and rPLU6 for genus specification, rFAL1, rFAL2, and rVIV1, rVIV2 forP. falciparumandP. vivaxdetection, respectively. The results showed that 126 (84.6%), 16 (10.7%), and 7 (4.7%) out of 149 cases were positive forP. vivax,P. falciparum,and mixed infections, respectively, by microscopy. The PCR indicated that 95 (63.7%), 15 (10.1%), and 22 (14.8%) cases were infected withP. vivax,P. falciparum,and mixed mentioned species, respectively, and 17 (11.4%) cases were uninfected. Our results confirmed the considerable sensitivity of nested PCR for detection of the mixed infections. Simultaneous application of PCR even based on microscopy slides can facilitate access to the highest level of confidence in malaria researches.
Oversimplification and Overstandardization in Biological Methods: Sperm Bioassays in Ecotoxicology as a Case of Study and a Proposal for Their Reformulation
Authors: Murado M. A. , Prieto M. A.
Published: February 2014

An interesting toxicological bioassay (fertilization inhibition in sea urchin) uses as assessment criterion a variable (fertilization ratio) whose variation with time creates two types of difficulties. First, it fails to distinguish between the toxic effect and the spontaneous decline in the sperm activity, causing some inconsistencies. Second, the sensitivity of the fertilization ratio to many other variables of the system requires a complex standardization, constraining the achievement of the method without solving its main problem. Our proposal consists of using a parameter (sperm half-life) as the response of the assay, and describing explicitly the behavior of the system as a simultaneous function of dose and time. This new focus is able to solve the problematic character of the results based on the fertilization ratio and by using the same data set which is required by the conventional approach; it simplifies the protocol, economizes experimental effort, provides unambiguous and robust results, and contributes to the detection of an artefactual temperature effect, which is not very evident under the usual perspective. Potential application of this new approach to the improvement of other formally similar bioassays is finally suggested.
UML Profile for Mining Process: Supporting Modeling and Simulation Based on Metamodels of Activity Diagram
Authors: Giubergia Andrea , Riesco Daniel , Gil-Costa Verónica , Printista Marcela
Published: February 2014

An UML profile describes lightweight extension mechanism to the UML by defining custom stereotypes, tagged values, and constraints. They are used to adapt UML metamodel to different platforms and domains. In this paper we present an UML profile for models supporting event driving simulation. In particular, we use the Arena simulation tool and we focus on the mining process domain. Profiles provide an easy way to obtain well-defined specifications, regulated by the Object Management Group (OMG). They can be used as a presimulation technique to obtain solid models for the mining industry. In this work we present a new profile to extend the UML metamodel; in particular we focus on the activity diagram. This extended model is applied to an industry problem involving loading and transportation of minerals in the field of mining process.
The Prevention of Postmenopausal Osteoporotic Fractures: Results of the Health Technology Assessment of a New Antiosteoporotic Drug
Authors: de Waure Chiara , Specchia Maria Lucia , Cadeddu Chiara , Capizzi Silvio , Capri Stefano , Di Pietro Maria Luisa , Veneziano Maria Assunta , Gualano Maria Rosaria , Kheiraoui Flavia , La Torre Giuseppe , Nicolotti Nicola , Sferrazza Antonella , Ricciardi Walter
Published: February 2014

Objective. The Health Technology Assessment (HTA) approach was applied to denosumab in the prevention of osteoporotic fractures in postmenopausal women.Method. Epidemiological, clinical, technical, economic, organizational, and ethical aspects were considered. Medical electronic databases were accessed to evaluate osteoporosis epidemiology and therapeutical approaches. A budget impact and a cost-effectiveness analyses were performed to assess economic implications. Clinical benefits and patient needs were considered with respect to organizational and ethical evaluation.Results. In Italy around four millions women are affected by osteoporosis and have a higher risk for fractures with 70,000 women being hospitalized every year. Bisphosphonates and strontium ranelate are recommended as first line treatment for the prevention of osteoporotic fractures. Denosumab is effective in reducing vertebral, nonvertebral, and hip/femoral fractures with an advantage of being administered subcutaneously every six months. The budget impact analysis estimated a reduction in costs for the National Health Service with the introduction of denosumab. Furthermore, the economic analysis demonstrated that denosumab is cost-effective in comparison to oral bisphosphonates and strontium ranelate. Denosumab can be administered in outpatients by involving General Practitioners in the management. Ethical evaluation is positive because of its efficacy and compliance.Conclusion. Denosumab could add value in the prevention of osteoporotic fractures.
View-Dependent Tessellation and Simulation of Ocean Surfaces
Authors: Puig-Centelles Anna , Ramos Francisco , Ripolles Oscar , Chover Miguel , Sbert Mateu
Published: February 2014

Modeling and rendering realistic ocean scenes have been thoroughly investigated for many years. Its appearance has been studied and it is possible to find very detailed simulations where a high degree of realism is achieved. Nevertheless, among the solutions to ocean rendering, real-time management of the huge heightmaps that are necessary for rendering an ocean scene is still not solved. We propose a new technique for simulating the ocean surface on GPU. This technique is capable of offering view-dependent approximations of the mesh while maintaining coherence among the extracted approximations. This feature is very important as most solutions previously presented must retessellate from the initial mesh. Our solution is able to use the latest extracted approximation when refining or coarsening the mesh.
Comparative Pharmacokinetics of Levofloxacin in Healthy and Renal Damaged Muscovy Ducks following Intravenous and Oral Administration
Authors: Aboubakr Mohamed , Soliman Ahmed
Published: February 2014

The pharmacokinetics aspects of levofloxacin were studied in healthy and experimentally renal damaged Muscovy ducks after single intravenous (IV) and oral (PO) dose of 10 mg kg−1 bwt. Following IV administration, elimination half-life (t1/2(β)) and mean residence time (MRT) were longer in renal damaged ducks than in healthy ones. Total clearance(Cltot)in renal damaged ducks (0.20 L kg−1 h−1) was significantly lower as compared to that in healthy ones (0.41 L kg−1 h−1). Following PO administration, the peak serum concentration(Cmax)was higher in renal damaged than in healthy ducks and was achieved at maximum time(tmax)of 2.47 and 2.05 h, respectively. The drug was eliminated (t1/2(el)) at a significant slower rate (3.94 h) in renal damaged than in healthy ducks (2.89 h). The pharmacokinetic profile of levofloxacin is altered in renal damaged ducks due to the increased serum levofloxacin concentrations compared with that in clinically healthy ducks. Oral administration of levofloxacin at 10 mg kg−1 bwt may be highly efficacious against susceptible bacteria in ducks. Also, the dose of levofloxacin should be reduced in renal damaged ducks. Pharmacokinetic/pharmacodynamic integration revealed significantly higher values forCmax/MIC and AUC/MIC ratios in renal damaged ducks than in healthy ones, indicating the excellent pharmacokinetic characteristics of levofloxacin in renal damaged ducks.
Better Postdiagnosis Diet Quality Is Associated with Reduced Risk of Death among Postmenopausal Women with Invasive Breast Cancer in the Women's Health Initiative
Authors: George Stephanie M. , Ballard-Barbash Rachel , Shikany James M. , Caan Bette J. , Freudenheim Jo L. , Kroenke Candyce H. , Vitolins Mara Z. , Beresford Shirley A. , Neuhouser Marian L.
Published: February 2014

Background: Few studies have evaluated whether adherence to dietary recommendations is associated with mortality among cancer survivors. In breast cancer survivors, we examined how postdiagnosis Healthy Eating Index (HEI)-2005 scores were associated with all-cause and cause-specific mortality.

Methods: Our prospective cohort study included 2,317 postmenopausal women, ages 50 to 79 years, in the Women's Health Initiative's Dietary Modification Trial (n = 1,205) and Observational Study (n = 1,112), who were diagnosed with invasive breast cancer and completed a food frequency questionnaire after being diagnosed. We followed women from this assessment forward. We used Cox proportional hazards models to estimate multivariate-adjusted HRs and 95% confidence intervals (CI) for death from any cause, breast cancer, and causes other than breast cancer, according to HEI-2005 quintiles.

Results: Over 9.6 years, 415 deaths occurred. After adjustment for key covariates, women consuming better quality diets had a 26% lower risk of death from any cause (HRQ4:Q1, 0.74; 95% CI, 0.55–0.99; Ptrend = 0.043) and a 42% lower risk of death from non–breast cancer causes (HRQ4:Q1, 0.58; 95% CI, 0.38–0.87; Ptrend = 0.011). HEI-2005 score was not associated with breast cancer death (HRQ4:Q1, 0.91; 95% CI, 0.60–1.40; Ptrend = 0.627). In analyses stratified by tumor estrogen receptor (ER) status, better diet quality was associated with a reduced risk of all-cause mortality among women with ER+ tumors (n = 1,758; HRQ4:Q1, 0.55; 95% CI, 0.38–0.79; Ptrend = 0.0009).

Conclusion: Better postdiagnosis diet quality was associated with reduced risk of death, particularly from non–breast cancer causes.

Impact: Breast cancer survivors may experience improved survival by adhering to U.S. dietary guidelines. Cancer Epidemiol Biomarkers Prev; 23(4); 575–83. ©2014 AACR.
EASL- and mRECIST-Evaluated Responses to Combination Therapy of Sorafenib with Transarterial Chemoembolization Predict Survival in Patients with Hepatocellular Carcinoma
Authors: Liu Lei , Wang Weijuan , Chen Hui , Zhao Yan , Bai Wei , Yin Zhanxin , He Chuangye , Jia Jia , Yang Man , Xia Jielai , Fan Daiming , Han Guohong
Published: February 2014

Purpose: Published studies have not investigated the suitability of Response Evaluation Criteria in Solid Tumors (RECIST), European Association for the Study of the Liver (EASL) criteria, and modified RECIST (mRECIST) for assessing the response of patients with hepatocellular carcinoma to treatment with sorafenib combined with transarterial chemoembolization. Here, we aimed to define the earliest time at which the response to combination therapy could be accurately assessed and validate the prognostic value of these criteria at this early posttherapy time point.

Experimental Design: A total of 114 consecutive patients with hepatocellular carcinoma receiving combination therapy were retrospectively enrolled. The therapy response at different time points was assessed using RECIST, EASL, and mRECIST. Cox regression analysis and Kaplan–Meier curves were used to assess overall survival (OS) in the responders and nonresponders.

Results: At the third follow-up (median, 94 days; range, 89–102 days) after therapy, the response rates obtained using EASL (50.6%) and mRECIST (51.6%) were greater than that obtained using RECIST (16.5%). The agreement was strong between the mRECIST and EASL results (k = 0.9) but weak between mRECIST and RECIST (k = 0.3). The EASL and mRECIST responses significantly correlated with survival. Risk reductions of 52% and 50% were observed for EASL and mRECIST responders, respectively, compared with nonresponders. However, no significant association between the treatment response and survival was observed using RECIST.

Conclusions: The earliest time to evaluate the response to combination therapy is 3 months (median, 94 days) after therapy. EASL and mRECIST responses are independent predictors for OS at this early time point. Clin Cancer Res; 20(6); 1623–31. ©2014 AACR.
Glaucoma: Present Challenges and Future Trends
Authors: Bettin Paolo , Di Matteo Federico
Published: February 2014

The authors indicate four key issues which, in their opinion, represent the most stimulating challenges in the field of glaucoma today, and describe the present approaches and the developments that can be expected or advised in the near future: (1) Glaucoma is often undiagnosed or diagnosed too late. Accurate detection is crucial to correctly recognize and treat affected subjects, thus reducing the disability and the social burden of the disease. Is glaucoma screening advisable and cost-effective? What strategies can be implemented to achieve an earlier diagnosis? (2) What role can genetics play in glaucoma clinics? (3) What are the fundamentals and the limits of medical hypotensive and nonhypotensive treatment of glaucoma today, and what novelties could be introduced in the next few years? (4) What are the current and future options for glaucoma surgery? Should we aim at reducing aqueous production or at enhancing aqueous outflow? What are the success figures and the pros and cons of ab externo procedures with external filtration (trabeculectomy, nonpenetrating techniques and glaucoma drainage devices) and of ab externo techniques with internal filtration (viscocanalostomy and canaloplasty)? Will microinvasive procedures ever play a role in the treatment of the disease? These questions and the possible future developments in the management of glaucoma are discussed critically, based on the current clinical state of the art, on a review of the literature, and on an everyday experience in a busy university hospital glaucoma service.
Translational Findings on Brain-Derived Neurotrophic Factor and Anxiety: Contributions from Basic Research to Clinical Practice
Authors: Domingos da Silveira da Luz Anna Claudia , Pereira Dias Gisele , do Nascimento Bevilaqua Mário Cesar , Cocks Graham , Gardino Patricia Franca , Thuret Sandrine , Nardi Antonio Egidio
Published: February 2014

Background/Aims: Anxious responses are evolutionarily adaptive, but excessive fear can become disabling and lead to anxiety disorders. Translational models of anxiety might be useful sources for understanding the neurobiology of fear and anxiety and can contribute to future proposals of therapeutic intervention for the disorders studied. Brain-derived neurotrophic factor (BDNF), which is known for its importance on neuroplasticity and contextual memory, has emerged as a relevant element for emotional memory. Recent studies show that the Val66Met BDNF polymorphism correlates with various psychiatric disorders, including anxiety, but there are several differences between experimental and clinical studies. Methods: In this work, we review the literature focused on the BDNF Val66Met polymorphism and anxiety, and discuss biological findings from animal models to clinical studies. Results: As occurs with other psychiatric disorders, anxiety correlates with anatomical, behavioral and physiological changes related to the BDNF polymorphism. In animal studies, it has been shown that a significant decrease in regulated secretion from both BDNFVal/Met and BDNFMet/Met neurons represented a significant decrease in available BDNF. Conclusion: These studies suggest that developing pharmacological strategies facilitating the release of BDNF from synapses or prolongation of the half-life of secreted BDNF may improve the therapeutic responses of humans expressing the BDNF polymorphism.
Exhaled Breath Temperature in Asthmatics and Controls after Eucapnic Voluntary Hyperventilation and a Methacholine Challenge Test
Authors: Svensson Henning , Bjermer Leif , Tufvesson Ellen
Published: February 2014

Background: It has been suggested that exhaled breath temperature (EBT) is increased in asthmatic subjects. Objectives: Our aim was to investigate EBT in asthmatics compared to healthy controls before and after eucapnic voluntary hyperventilation (EVH) and a methacholine challenge test (MCT). Methods: A total of 26 asthmatics and 29 healthy controls were included. Forced expiratory volume in 1 s (FEV1), EBT and oral, axillary and auricular temperatures were measured before and after EVH and MCT. Results: FEV1 % predicted (%p) was significantly lower in asthmatic subjects compared to healthy controls at all time points. EBT was significantly increased in all subjects 15-30 min after EVH and 5-45 min after MCT. Oral temperature displayed a similar pattern of increase, in contrast to axillary and auricular temperature, and correlated with EBT before and after both of the challenge tests. EBT after 5 min correlated with the largest drop in FEV1%p after EVH in asthmatic subjects. No significant differences or changes in EBT were found when comparing asthmatics to healthy controls before or after any of the tests. Conclusions: EBT is increased after both EVH and MCT, possibly reflecting a vascular response. This is related to both the fall in FEV1 and to oral temperature, suggesting an effect on the whole respiratory tract including the oral cavity. No differences in EBT are seen between asthmatics and healthy controls, indicating that the increase in EBT is mainly physiological rather than pathophysiological.
Androgens Contribute to Age-Associated Changes in Peripheral T-Cell Homeostasis Acting in a Thymus-Independent Way
Authors: Arsenović-Ranin Nevena , Kosec Duško , Pilipović Ivan , Bufan Biljana , Stojić-Vukanić Zorica , Radojević Katarina , Nacka-Aleksić Mirjana , Leposavić Gordana
Published: February 2014

Objective: Considering a causal role of androgens in thymic involution, age-related remodeling of peripheral T-cell compartments in the absence of testicular hormones was evaluated. Methods: Rats were orchidectomized (ORX) at the age of 1 month, and T-peripheral blood lymphocytes (PBLs) and splenocytes from young (75-day-old) and aged (24-month-old) rats were examined for differentiation/activation and immunoregulatory marker expression. Results: In ORX rats, following the initial rise, the counts of CD4+ and CD8+ PBLs diminished with aging. This reflected the decline in thymic export as shown by recent thymic emigrant (RTE) enumeration. Orchidectomy increased the count of both of the major T-splenocyte subsets in young rats, and they (differently from controls) remained stable with aging. The CD4+:CD8+ T-splenocyte ratio in ORX rats shifted towards CD4+ cells compared to age-matched controls. Although in the major T-cell subsets in the blood and spleen from aged ORX rats the numbers of RTEs were comparable to the corresponding values in age-matched controls, the numbers of mature naïve and memory/activated cells substantially differed. Compared with age-matched controls, in aged ORX rats the numbers of CD4+ mature naïve PBLs and splenocytes were reduced, whereas those of CD4+ memory/activated cells (predictive of early mortality) were increased. Additionally, in spleens from aged ORX rats, despite unaltered thymic export, CD4+CD25+FoxP3+ and natural killer T cell counts were greater than in age-matched controls. Conclusion: (i) Age-related decline in thymopoietic efficacy is not dependent on androgen presence, and (ii) androgens are involved in the maintenance of peripheral T-cell (particularly CD4+ cell) homeostasis during aging.
Uric Acid - Key Ingredient in the Recipe for Cardiorenal Metabolic Syndrome
Authors: Chaudhary Kunal , Malhotra Kunal , Sowers James , Aroor Annayya
Published: February 2014

Elevated serum uric acid levels are a frequent finding in persons with obesity, hypertension, cardiovascular and kidney disease as well as in those with the cardiorenal metabolic syndrome (CRS). The increased consumption of a fructose-rich Western diet has contributed to the increasing incidence of the CRS, obesity and diabetes especially in industrialized populations. There is also increasing evidence that supports a causal role of high dietary fructose driving elevations in uric acid in association with the CRS. Animal and epidemiological studies support the notion that elevated serum uric acid levels play an important role in promoting insulin resistance and hypertension and suggest potential pathophysiological mechanisms that contribute to the development of the CRS and associated cardiovascular disease and chronic kidney disease. To this point, elevated serum levels of uric acid appear to contribute to impaired nitric oxide production/endothelial dysfunction, increased vascular stiffness, inappropriate activation of the renin-angiotensin-aldosterone system, enhanced oxidative stress, and maladaptive immune and inflammatory responses. These abnormalities, in turn, promote vascular, cardiac and renal fibrosis as well as associated functional abnormalities. Small clinical trials have suggested that uric acid-lowering therapies may be beneficial in such patients; however, a consensus on the treatment of asymptomatic hyperuricemia is lacking. Larger randomized controlled trials need to be performed in order to critically evaluate the beneficial effect of lowering serum uric acid in patients with the CRS and those with diabetes and/or hypertension.
Meta-Analyses to Investigate Gene-Environment Interactions in Neuroepidemiology
Authors: van der Mei I.A.F. , Otahal P. , Simpson Jr. S. , Taylor B. , Winzenberg T.
Published: February 2014

Background: Most chronic neurological diseases are caused by a combination of multiple genetic and environmental factors. Increasingly, gene-environment interactions (GxE) are being examined, providing opportunities to combine studies systematically using meta-analysis. Methods: Systematic review of the literature on how to examine GxE using observational study designs, and how to conduct a meta-analysis of studies on GxE. Results: Most methods and challenges related to a standard meta-analysis apply to a GxE meta-analysis. There are, however, some substantive differences. With GxE, there is the capability of using a case-only design. Research on GxE interactions may be more prone to publication bias, since interactions are usually not the primary hypothesis and only ‘exciting' significant GxE findings are reported out of a range of secondary analyses. In disease aetiology research, there has been debate whether to measure interaction on a multiplicative or additive scale. There are some significant challenges associated with measuring interaction on an additive scale, and thus the uptake of the measures of additive interaction has been limited. As a result, the methods of analysing interaction have been less consistent and reporting has been highly variable. We suggest using the STROBE/STREGA reporting guidelines to allow evaluation of interaction on both scales. Conclusions: We identified a number of differences of a GxE meta-analysis over a standard meta-analysis. Awareness of these issues is important. Using established reporting guidelines for GxE studies is recommended. The development of consortia for neurological disorders that include both genetic and environmental data might offer benefits for GxE meta-analyses in the future.
Familial Coaggregation of Alzheimer's Disease and Parkinson's Disease: Systematic Review and Meta-Analysis
Authors: Feldman Adina L. , Johansson Anna L.V. , Lambert Paul C. , Sieurin Johanna , Yang Fei , Pedersen Nancy L. , Wirdefeldt Karin
Published: February 2014

Background: Familial aggregation has been shown for Alzheimer's disease (AD) and Parkinson's disease (PD) separately, and it has been hypothesized that these diseases also coaggregate in families. Methods: The authors investigated familial coaggregation of AD and PD by conducting a systematic review and meta-analysis. PubMed was searched for relevant studies published through the end of October 2012. Three independent investigators screened publications and extracted data. Relative risk estimates of AD risk associated with family history of PD or parkinsonism, or PD risk associated with family history of AD or dementia, were summarized into metaestimates using random effects models. Heterogeneity and publication bias were tested using Higgins' and Egger's tests, respectively. Results: We included 16 studies in the review, with 14 included in any meta-analysis. AD risk associated with family history of PD yielded a summary hazard ratio of 1.18 (95% CI: 1.00-1.39) based on 5 reconstructed cohort studies and a summary odds ratio (OR) of 1.40 (95% CI: 0.92-2.12) based on 7 case-control studies. PD risk associated with family history of AD yielded a summary OR of 0.75 (95% CI: 0.49-1.16) based on 3 studies. There was no significant heterogeneity among studies, nor significant publication bias. Conclusions: There may be familial coaggregation of AD and PD, although the association was modest and only apparent when studying AD risk associated with family history of PD.
A Prime Time for Trained Immunity: Innate Immune Memory in Newborns and Infants
Authors: Levy Ofer , Wynn James L.
Published: February 2014

The newborn and infant periods of early life are associated with heightened vulnerability to infection. Limited antigen exposure and distinct adaptive immune function compared to the adult places a greater burden on innate immunity for host defense to microbial challenge during this time. Trained immunity describes the phenomenon of augmented innate immune function following a stimulus that is not specific to the original stimulus. We review the concept of trained immunity in the context of the newborn's unique innate immune system function, the preclinical and clinical evidence that supports the tenet of innate immune memory in early life, and potential consequences of altered innate immune host responses.
Lung Congestion as a Risk Factor in End-Stage Renal Disease
Authors: Zoccali Carmine , Tripepi Rocco , Torino Claudia , Bellantoni Marianna , Tripepi Giovanni , Mallamaci Francesca
Published: February 2014

Background: Lung congestion is emerging as a pervasive, insidious problem in end-stage renal disease (ESRD) patients on dialysis. Summary: Chest ultrasound (US), a novel, easy-to-perform, cheap technique, which is currently applied for objective monitoring of pulmonary congestion in patients with heart failure in Europe, allows reliable quantification of lung water in clinical practice. Before hemodialysis (HD), about 60% of ESRD patients displayed moderate-severe lung congestion and this alteration is frequently asymptomatic. Lung congestion is reduced but not abolished by ultrafiltration dialysis, and about one third to one fourth of patients still have excessive lung water after dialysis. Lung congestion is also prevalent in patients on peritoneal dialysis (PD), and in apparently asymptomatic HD and PD patients this alteration is strongly associated with poor physical performance. Lung water in HD patients correlates in an inverse fashion with echocardiographic parameters of systolic and diastolic function, but it is only weakly related with hydration status measured by bioimpedance analysis. Moderate-severe lung congestion is a strong predictor of death and cardiovascular events and provides prognostic information independent of NYHA class, and traditional and nontraditional risk factors in ESRD patients on HD. Key Messages: Systematic application of chest US in ESRD patients shows that hidden or clinically manifest lung congestion is exceedingly frequent in this population. This alteration largely reflects left ventricular disorders superimposed on volume overload. The clinical usefulness of systematic application of chest US in ESRD remains to be tested in a formal clinical trial.
Nocturnal Deterioration after Ischemic Stroke and Autonomic Dysfunction: Hypothesis and Implications
Authors: Palamarchuk Iryna , Kimpinski Kurt , Lippert Corbin , Hachinski Vladimir
Published: February 2014

Background: A significant number of patients admitted to hospital after acute ischemic stroke deteriorate clinically. Deterioration is generally noted within the first 48 h after stroke onset. The mechanisms leading to this deterioration are not fully understood. Summary: One potential cause of this deterioration may be altered or impaired autonomic function. We expect the hemodynamic changes regulated by the autonomic nervous system that are dysregulated after stroke to be exaggerated during sleep, resulting in arrhythmia and blood pressure fluctuations in these patients. Such physiological changes could result in worsening the overall outcome of the ischemic stroke patient or in sudden death. Therefore, it is necessary to summarize yet unrelated observations and hypothesize on their individual effects and interactions as they relate to poststroke deterioration. Key Messages: If the hypothesis is correct that dysautonomia occurs to the degree that it affects clinical outcomes negatively, this would have important implications for the prevention of neurological deterioration and sudden death after ischemic stroke.
Tumor Volume as a Prognostic Factor in Resectable Malignant Melanoma
Authors: Voss Barbara , Wilop Stefan , Jonas Stephan , El-Komy M.H.M. , Schaller Joerg , von Felbert Verena , Megahed Mosaad
Published: February 2014

Background: Vertical tumor thickness according to Breslow and histological ulceration are still the most powerful predictors for the clinical outcome of resectable cutaneous malignant melanoma (MM) without lymph node infiltration. It has been proposed that tumor volume in MM may also be of prognostic relevance. Methods: We retrospectively analyzed the prognostic impact of tumor volume and other established risk factors in 122 MM patients with a median follow-up period of 39.7 months. Results: We found the logarithmic tumor volume to be a better prognostic factor compared to Breslow tumor thickness in multivariate analysis. MM with a tumor volume below a threshold of 140 mm3 had a significantly higher relapse-free survival after 5 years of 98% compared to 47% in larger MMs (p < 0.0001). Conclusion: In some melanomas with a low tumor thickness, a higher tumor volume appeared to be linked to a higher risk of disease recurrence. Inclusion of tumor volume into the risk assessment of resectable MM may be of benefit in the future.
Motility Abnormalities in Irritable Bowel Syndrome
Authors: DuPont Andrew W. , Jiang Zhi-Dong , Harold Stephen A. , Snyder Ned , Galler Greg W. , Garcia-Torres Francisco , DuPont Herbert L.
Published: February 2014

Background/Aims: The intestinal pathophysiology in irritable bowel syndrome (IBS) is largely unknown. The lactulose breath test has been used to identify small bowel bacterial overgrowth in these patients. Methods: We studied intestinal transit in patients with IBS using of the SmartPill® (SP) wireless pH/pressure recording capsule and performed lactulose breath tests to look for physiologic abnormalities. Results: A total of 35/46 (76%) of the IBS patients had prolonged gastric emptying times. Constipation-predominant disease was associated with prolonged gut transit times. The mean hours ± SD for colonic transit time in the constipation group was 71.7 ± 61.1 (n = 13) compared with 22.5 ± 14.9 (n = 14) for diarrhea-predominant and 26.4 ± 21.5 (n = 20) for mixed clinical subtype (p = 0.0010). No correlation between small bowel transit time and abnormal breath hydrogen or methane excretion in the 46 combined patients with IBS was seen. Conclusions: Delayed gastric emptying was identified in IBS and in some patients may contribute to at least a component of their symptoms. Constipation-predominant IBS is associated with prolonged gut transit times. Otherwise, transit abnormalities do not appear to be important in IBS. Intestinal transit did not correlate with breath test results.
Definitions and Outcomes of Nutritional Interventions in Children with Respiratory Infections: The Approach of the COMMENT Initiative
Authors: Guarino Alfredo , Bruzzese Eugenia , Lo Vecchio Andrea , Dagan Ron , Tsolia Maria
Published: February 2014

Background/Aims: This study is aimed at assessing definitions and outcomes used to measure the effects of nutrition in the prevention and treatment of respiratory tract infections in childhood. Methods: We reviewed clinical trials studying the impact of nutritional interventions on upper and lower respiratory tract infections (URTI and LRTI), focusing on definitions and key outcomes. Results: Fifty trials were included (46 on prevention and 4 on treatment). The definitions of respiratory infections were highly heterogeneous. In 15 of the trials, URTI or LRTI were diagnosed by a pediatrician. In 30 trials, definitions were based on symptoms reported by family members or field-workers only. Five trials did not provide any specific definition. Incidence was the most common outcome measure reported in the trials on prevention, and duration and illness severity were the most common in the treatment trials. Conclusions: The results showed a major heterogeneity with the use of a wide array of different definitions and clinical end points. To overcome these limitations, outcome measures might be differentiated into two categories: ‘direct outcomes' in which respiratory infections are diagnosed and monitored by physicians according to rigorous definitions and ‘indirect outcomes' (e.g. chest X-ray, antibiotic prescription and hospitalizations) to assess the burden of respiratory illnesses. Agreement on standard definitions and end points is needed to drive future trials.
Pharmacological Approach to Diabetic Macular Edema
Authors: Bandello F. , Casalino G. , Loewenstein A. , Goldstein M. , Pelayes D. , Battaglia Parodi M.
Published: February 2014

Diabetic macular edema (DME) is a highly prevalent cause of vision loss and has a remarkable impact on public health, and on the quality of life of diabetic patients. Even though laser photocoagulation has been the standard of care for decades, a substantial group of patients are unresponsive and fail to improve after laser treatment. Recently, new pharmacological approaches based on the use of intravitreal drugs, such as corticosteroids and anti-vascular endothelial growth factor, have revolutionized the treatment of DME. The use of intravitreal drugs is supported by the improvement in visual acuity reported by several clinical trials and can limit the potentially destructive effects of the laser treatment. Encouraging results also emerged from studies evaluating the use of a combination therapy, or the association of intravitreal drugs and laser treatment. This review aims at providing a brief synopsis of the main investigations regarding the current pharmacological approach to DME.
Michel Dumas and Pierre-Marie Preux: Promoting Tropical Neurology Silently - The Gist of Their Contributions
Authors: Bhalla Devender
Published: February 2014

This article presents the contribution by two senior French Neurologists over the past three decades in building, developing and promoting ‘tropical neurology' in a number of neglected countries of Asia, Africa and Latin America. It talks about the ‘human, dedicational and contributive value' of these two experts who do not come from an English-speaking world. It highlights meaningful changes that have been achieved in different tropical countries as a result of their direct contribution. This overview may likely be a cause for learning and motivation to others to really work in and for tropical countries, where a large proportion of global health burden is to be found.