Assessing the external benefits of contaminated soil remediation in Korea: a choice experiment study

Abstract

Korean government has made and will continue to make a considerable investment in contaminated soil remediation to rectify the problems that arise from soil pollution. Quantitative information on the benefits of contaminated soil remediation is widely demanded by the public as well as the government. This article aims to assess the external benefits of contaminated soil remediation. A survey of 1000 randomly selected households was undertaken in Korea. The results show that the marginal willingness to pay values for a 1% decrease in human health hazard, a 1% improvement in biodiversity restoration, and 1000 new job creation by contaminated soil remediation are estimated to be KRW 204 (USD 0.17), 593 (0.50), and 238 (0.20) per household per year. The findings can provide policy-makers with useful information for both evaluating and planning the contaminated soil remediation.

Basal Cell Carcinoma, PART II: Contemporary Approaches to Diagnosis, Treatment, and Prevention

As the most common human cancer worldwide and continuing to increase in incidence, basal cell carcinoma is associated with significant morbidity and cost. Continued advances in research have refined both our insight and approach to this seemingly ubiquitous disease. This 2-part continuing medical education article will provide a comprehensive and contemporary review of basal cell carcinoma. Part II of this series will present both standard of care and newly developed approaches to diagnosis, treatment, and prevention of this disease.

Basal Cell Carcinoma: Part 1

As the most common human cancer worldwide and continuing to increase in incidence, basal cell carcinoma is associated with significant morbidity and cost. Continued advances in research have refined both our insight and approach to this seemingly ubiquitous disease. This 2-part continuing medical education article will provide a comprehensive and contemporary review of basal cell carcinoma. Part I of this series will describe our current understanding of this disease in regards to epidemiology, cost, clinical and histopathologic presentations, carcinogenesis, natural history, and disease associations.

Use and overuse of triptans in Austria – a survey based on nationwide healthcare claims data

To evaluate triptan use and overuse as well as prescription patterns in Austria based on a nationwide healthcare database because data on triptan use and overuse in Austria is missing.

How high the sky? Rumfitt on the (putative) indeterminacy of the set-theoretic universe

Abstract

This comment focuses on Chapter 9 of The Boundary Stones of Thought and the argument, due to William Tait, that Ian Rumfitt there sustains for the indeterminacy of set. I argue that Michael Dummett's argument, based on the notion of indefinite extensibility and set aside by Rumfitt, provides a more powerful basis for the same conclusion. In addition, I outline two difficulties for the way Rumfitt attempts to save classical logic from acknowledged failures of the principle of bivalence, one specifically for his treatment of the set-theoretic case, the other of more general bearing but especially germane to the case of vagueness.

The epistemic significance of political disagreement

Abstract

The degree of doxastic revision required in response to evidence of disagreement is typically thought to be a function of our beliefs about (1) our interlocutor's familiarity with the relevant evidence and arguments, and their intellectual capacities and virtues, relative to our own, or (2) the expected probability of our interlocutor being correct, conditional on our disagreeing. While these two factors are typically used interchangeably, I show that they have an inverse correlation in cases of disagreement about politically divisive propositions. This presents us with a puzzle about the epistemic impact of disagreement in these cases. The most significant disagreements on (1) are the least significant disagreements on (2), and vice versa. I show that assessing the epistemic status of an interlocutor by reference to either (1) or (2) has uncomfortable consequences in these cases. I then argue that this puzzle cannot be escaped by claiming that we usually have dispute-independent reason to reject the significance of politically charged disagreement altogether.

Improved recovery from limb ischaemia by delivery of an affinity-isolated heparan sulphate

Abstract

Peripheral arterial disease is a major cause of limb loss and its prevalence is increasing worldwide. As most standard-of-care therapies yield only unsatisfactory outcomes, more options are needed. Recent cell- and molecular-based therapies that have aimed to modulate vascular endothelial growth factor-165 (VEGF₁₆₅) levels have not yet been approved for clinical use due to their uncertain side effects. We have previously reported a heparan sulphate (termed HS7) tuned to avidly bind VEGF₁₆₅. Here, we investigated the ability of HS7 to promote vascular recovery in a murine hindlimb vascular ischaemia model. HS7 stabilised VEGF₁₆₅ against thermal and enzyme degradation in vitro, and isolated VEGF₁₆₅ from serum via affinity-chromatography. C57BL6 mice subjected to unilateral hindlimb ischaemia injury received daily intramuscular injections of respective treatments (n = 8) and were assessed over 3 weeks by laser Doppler perfusion, magnetic resonance angiography, histology and the regain of function. Mice receiving HS7 showed improved blood reperfusion in the footpad by day 7. In addition, they recovered hindlimb blood volume two- to fourfold faster compared to the saline group; the greatest rate of recovery was observed in the first week. Notably, 17% of HS7-treated animals recovered full hindlimb function by day 7, a number that grew to 58% and 100% by days 14 and 21, respectively. This was in contrast to only 38% in the control animals. These results highlight the potential of purified glycosaminoglycan fractions for clinical use following vascular insult, and confirm the importance of harnessing the activity of endogenous pro-healing factors generated at injury sites.

Functionalized and grafted TiO 2 , CeO 2 , and SiO 2 nanoparticles—ecotoxicity on Daphnia magna and relevance of ecofriendly polymeric networks

Abstract

Effects of functionalization and grafting of TiO₂, CeO₂, and SiO₂ nanoparticles (NPs) were investigated, and toxicity of pristine, functionalized, and grafted NP towards Daphnia magna was measured. Surface functionalization of NP with amine groups decreased hydrophobicity of NP. When NPs were hydrophilic, they were less toxic than hydrophobic NP towards D. magna. Grafting agents influenced toxicity: no toxicity of NP was observed when bio-based and hydrogenated synthetic polymers were used, whereas perfluorinated polymers induced a higher toxicity.

Alexander Gebharter: Causal Nets, Interventionism, and Mechanisms. Philosophical Foundations and Applications

Highlights from the Literature

Forthcoming Meetings

How should adult patients with neurofibromatosis 1 be managed?

Among familial tumor syndromes, neurofibromatosis 1 (NF-1) is the most prevalent, affecting about 1 in 3000 births. The disorder leads to a microdeletion in the gene coding for neurofibromin, which is a negative regulator of the Ras oncogene signal transduction pathway. The gene is situated on 17q11.2, and mutation is transmitted as an autosomal dominant trait. However, half of affected individuals are spontaneous mutations.

Flexible occurrent control

Abstract

There has recently been much interest in the role of attention in controlling action. The role has been mischaracterized as an element in necessary and sufficient conditions on agential control. In this paper I attempt a new characterization of the role. I argue that we need to understand attentional control in order to fully understand agential control. To fully understand agential control we must understand paradigm exercises of agential control. Three important accounts of agential control—intentional, reflective, and goal-represented control—do not fully explain such exercises. I argue that understanding them requires understanding how deployments of visual attention implement flexible occurrent control, or a capacity to flexibly adjust the degree of control that individuals exercise over their actions. While such deployments of attention are neither necessary nor sufficient for exercising agential control, they constitute an attentional skill for controlling action, understanding which is central to fully understanding agential control. We can appreciate its centrality if we appreciate that this attentional skill for controlling action is plausibly crucial to acting non-negligently.

Ameliorative effect of ginseng extract on phthalate and bisphenol A reprotoxicity during pregnancy in rats

Abstract

Phthalates (such as DEHP) and bisphenol A (BPA) are widely used chemicals in plastics manufacturing and exert public health concerns as endocrine disrupters. This study was designed to investigate the deleterious effect of DEHP and BPA on endocrine profile of pregnant female rats and the combined treatment with ginseng extract (Panax ginseng). Seventy-two pregnant rats were divided into six groups (control, ginseng, DEHP, BPA, Gin + DEHP, and Gin + BPA), 12 females per each group. The drugs were supplemented from pregnancy day 0 until day 20. Determination of serum sex hormones (testosterone, progesterone, and estradiol) were determined on days 4, 10, and 20 of pregnancy. mRNA transcripts of STAR, HSD17B3, CYP17, AKT1, and PTEN were relatively quantified against ACTB in the ovary and placenta of days 10 and 20 pregnant females by relative quantitative polymerase-chain reaction (RQ-PCR). DEHP and BPA significantly decreased the endocrine profile of testosterone, progesterone, and estradiol of days 10 and 20 of pregnant females. Combined administration of these chemicals along with ginseng extracts has returned the hormones to normal levels when compared with the control group. The ovarian and placental CYP17 and HSD17B3 mRNA transcripts showed variable expression pattern in both tissues and they were significantly affected by DEHP and BPA administration, concomitantly correlating to STAR, AKT1, PTEN, progesterone, and testosterone levels on pregnancy days 10 and 20. The results confirm the reprotoxicity of DEHP and BPA as endocrine disruptors and indicate that ginseng could be used to alleviate the toxic effects of these chemicals.

It is time to rethink weight loss in cancer

Nihilism is all too common at the intersection of nutrition and cancer care. It is far too easy to see a person in clinic with cancer and weight loss, and to reflect silently on the apparent inevitability of this scenario. In the busy clinical environment, our focus moves quickly to other seemingly more pressing (or tangible) issues in the consultation. Because we are so used to seeing people lose weight, there is a risk that other causes of weight loss may be overlooked, including poor nutritional status (whether recent or long term), cachexia, or both.

The case for ‘successfully’ treating hormone naïve metastatic prostate cancer

It was one of those exciting first days of clinical rotation in medical school that remain vibrant when reminiscing our 'induction' into medicine. Our instructor presented a gentleman with a rare surgical complication and asked the group the incidence. We were extremely excited to unanimously agree 1% only to be reprimanded by the tone of his response: you obviously did your homework but keep in mind for this gentleman it is currently at 100%.

Metastatic melanoma with balloon/histiocytoid cytomorphology after treatment with immunotherapy: A histologic mimic and diagnostic pitfall

Journal of Cutaneous Pathology, EarlyView.

Anatomic Variations of the Infraorbital Foramen in Caucasian Versus African American Skulls

Purpose: The infraorbital foramen (IOF) represents a highly conserved structure but demonstrates morphologic variability. The purpose of this study is to describe the IOF location, size, and supernumerary foramina in an African American population and compare it with a Caucasian population. Methods: Sixty African American and 60 Caucasian skulls from the Hamann-Todd collection of the Cleveland Museum of Natural History were studied. The primary outcome was the number of accessory IOF and measurements of the location, size, shape, and direction of each foramen. Pearson chi-square, t tests, Fisher exact test, and Wilcoxon rank sum tests were used to analyze the data. Results: The African American population had a smaller vertical IOF diameter (mean = 2.81 mm) compared with the Caucasian population (mean = 3.08 mm) on the right side (p

Orbital Decompression for Thyroid-Related Orbitopathy During the Quiescent Phase

Purpose: To describe historical and modern surgical approaches to orbital decompression in patients with thyroid-related orbitopathy in the quiescent phase. Methods: A literature review of published techniques using the National Institutes of Health PubMed database. Results: Historically, orbital decompression has been accomplished via transantral, transcranial, transnasal, and orbital approaches. Current techniques use predominately periocular incisions to achieve effective decompression and proptosis reduction. Based on exophthalmometry and desired proptosis reduction, the authors propose a graded surgical approach to decompression for thyroid orbitopathy beginning with fat reduction, followed by deep lateral orbit via a superior eyelid crease incision, then medial wall by retro-caruncular approach, then posterior medial orbital floor either via transconjunctival or swinging eyelid approach, and finally with lateral orbital rim removal by superior eyelid crease incision as needed. These approaches can result in a range of proptosis reduction of up to 10 mm. Conclusions: A structured approach to orbital decompression results in predictable and effective outcomes in proptosis reduction. Accepted for publication February 8, 2018. Supported by the Bell Charitable Foundation, Rancho Santa Fe, CA; Research to Prevent Blindness, New York, NY. None of the authors have any proprietary or commercial interest in any materials discussed in this article. Address correspondence and reprint requests to Don O. Kikkawa, M.D., Division of Oculofacial Plastic and Reconstructive Surgery, UC San Diego Department of Ophthalmology, Shiley Eye Institute, La Jolla, CA. E-mail: dkikkawa@ucsd.edu © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Thyroid Stimulating Hormone Receptor Antibodies in Thyroid Eye Disease—Methodology and Clinical Applications

Background: Thyroid stimulating hormone receptor antibodies (TSHR-Ab) cause autoimmune hyperthyroidism and are prevalent in patients with related thyroid eye disease (TED). Purpose: To provide a historical perspective on TSHR-Ab and to present evidence-based recommendations for clinical contemporary use. Methods: The authors review the recent literature pertaining to TSHR-Ab in patients with TED and describe the various immunoassays currently used for detecting TSHR-Ab and their clinical applications. Results: We provide a historical summary and description of the various methods used to detect TSHR-Ab, foremost, the functional TSHR-Ab. Increasing experimental and clinical data demonstrate the clinical usefulness of cell-based bioassays for measurements of functional TSHR-Ab in the diagnosis and management of patients with autoimmune TED and in the characterization of patients with autoimmune-induced hyperthyroidism and hypothyroidism. Thyroid stimulating hormone receptor antibodies, especially the functional stimulating antibodies, are sensitive, specific, and reproducible biomarkers for patients with autoimmune TED and correlate well with clinical disease activity and clinical severity. Unlike competitive-binding assays, bioassays have the advantage of indicating not only the presence of antibodies but also their functional activity and potency. Conclusions: Measurement of TSHR-Ab (especially stimulating antibodies) is a clinically useful tool for the management of patients with TED. Accepted for publication November 18, 2017. Tanja Diana has received speaker fees from Quidel, George J. Kahaly consults for and has received research grants and speaker fees from Quidel, U.S.A. Address correspondence and reprint requests to George J. Kahaly, M.D., Ph.D., Department of Medicine, Molecular Thyroid Research Laboratory, JGU Medical Center, Langenbeckstreet 1, Mainz 55131, Germany. E-mail: Kahaly@ukmainz.de. © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Thyrotropin Receptor Antibodies—An Overview

Purpose: Thyroid autoimmunity affects approximately 5% of the population, and its investigation relies heavily on the use of autoantibodies. Thyroid stimulating hormone receptor (TSHR) autoantibodies (TRAb) play a central role in the evaluation of Graves disease (GD), Graves ophthalmopathy (GO) and pretibial myxedema (PTM). However, there is still controversy regarding overall TRAb assay diagnostic accuracy and their prognostic utility. Methods: We reviewed and analyzed the literature reporting TRAb assays and their clinical utility. Results: Current assays measure the overall TRAb titer in a competitive manner (TSH binding inhibiting immunoglobulin assay) or biologic activity of the stimulating TSHR autoantibodies (thyroid stimulating immunoglobulin assay). Both types of assays have improved over time with advances in sensitivity and specificity. TRAb are particularly relevant in hyperthyroidism cases where use of iodinated contrast is not an option (e.g., pregnancy or recent use of iodinated contrast) or in cases of euthyroid eye disease, suspicious for GO. Third generation TRAb assays are useful for therapy selection in GD, prognostic predictions in GO and risk prediction for fetal and neonatal thyrotoxicosis. Discussion: Given the pathogenic role of TRAb, we expect that the future will bring useful evidence regarding their predictive role with respect to efficacy of therapeutic modalities for GO and PTM. We also hope to better understand the role of blocking and neutral antibodies against TSHR, and harness that ability for modulation of thyroid function or therapy of differentiated thyroid carcinoma managed with TSH suppression. Conclusions: Thyroid autoimmune diseases have seen tremendous gains in understanding their pathophysiology, largely antibody mediated. Better TRAb testing is becoming a springboard for providing individualized patient care. Accepted for publication November 18, 2017. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Marius Stan, M.D., Department of Medicine and Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN. E-mail: stan.marius@mayo.edu © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Radiotherapy for Active Thyroid Eye Disease

Purpose: To critically review the published literature on orbital radiotherapy as a treatment modality for thyroid eye disease (TED). Methods: A systematic review and analysis of the relevant published literature was performed. Results: Thyroid eye disease is an autoimmune condition that is amenable to treatments that modulate the immune response, including orbital radiotherapy (ORT). Ideal candidates for ORT are patients in the early, active phase of TED with moderate to severe, or rapidly progressive, disease, including patients with significant motility deficits and compressive optic neuropathy. Patients with progressive strabismus may also benefit. Patients with mild or inactive disease will not benefit from ORT when compared with the natural history of the disease. Orbital radiotherapy should generally be used in conjunction with corticosteroid therapy, with response to corticosteroids demonstrating the immunomodulatory therapeutic potential of ORT. When treating TED-compressive optic neuropathy, ORT may help obviate the need for urgent surgical decompression, or postpone it until the stable, inactive phase of the disease. Orbital radiotherapy treatment doses should approach 20 Gy in most cases, but lower doses may be considered in younger patients without significant dysmotility. The safety profile of ORT is well established, and side effects are minimal in appropriately selected patients. Conclusions: Radiotherapy is a safe and effective treatment for active TED in appropriately selected patients. Accepted for publication December 14, 2017. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Michael Kazim, M.D., Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University College of Physicians and Surgeons, 635 W. 165th Street, New York, NY. E-mail: mk48@cumc.columbia.edu © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Residue behavior and risk assessment of thifluzamide in the maize field ecosystem

Abstract

In the present work, the dissipation kinetics and final residue levels of thifluzamide in the maize field ecosystem were investigated. Using a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction combined with liquid chromatography-tandem mass spectrometric detection (LC-MS/MS), a rapid, sensitive, efficient, and reliable method for extraction and quantitative analysis of thifluzamide residues in maize grain, maize plant, and soil was developed. Satisfactory recoveries of 78.7–97.0% were achieved with relative standard deviations (RSDs) in the range of 1.6 to 8.2%. The limits of detection (LODs) and the limit of quantification (LOQ) were 0.002–0.005 and 0.010 mg kg⁻¹, respectively. The dissipation kinetics of thifluzamide in maize plant was well fitted by the first-order kinetic model with short half-lives of 0.19–0.22 days, while thifluzamide degraded slowly in soil with half-lives of 4.56–15.85 days. The final residues in maize grain, maize plant, and soil samples collected at the milk stage and the physiological maturity stage were no more than 0.010, 0.807, and 0.278 mg kg⁻¹, respectively. Given that no maximum residue limit (MRL) for thifluzamide in maize has been established, the safety of this fungicide application was estimated by a dietary risk assessment. The hazard quotient was 0.03%, which was substantially less than 1, indicating that the long-term risk induced by the thifluzamide application on maize at the recommended dose is negligible. These results help governments to develop regulations for the safe use of thifluzamide.

Particle Concentrations in Occupational Settings Measured with a Nanoparticle Respiratory Deposition (NRD) Sampler

Abstract

There is an increasing need to evaluate concentrations of nanoparticles in occupational settings due to their potential negative health effects. The Nanoparticle Respiratory Deposition (NRD) personal sampler was developed to collect nanoparticles separately from larger particles in the breathing zone of workers, while simultaneously providing a measure of respirable mass concentration. This study compared concentrations measured with the NRD sampler to those measured with a nano Micro Orifice Uniform-Deposit Impactor (nanoMOUDI) and respirable samplers in three workplaces. The NRD sampler performed well at two out of three locations, where over 90% of metal particles by mass were submicrometer particle size (a heavy vehicle machining and assembly facility and a shooting range). At the heavy vehicle facility, the mean metal mass concentration of particles collected on the diffusion stage of the NRD was 42.5 ± 10.0 µg/m³, within 5% of the nanoMOUDI concentration of 44.4 ± 7.4 µg/m³. At the shooting range, the mass concentration for the diffusion stage of the NRD was 5.9 µg/m³, 28% above the nanoMOUDI concentration of 4.6 µg/m³. In contrast, less favorable results were obtained at an iron foundry, where 95% of metal particles by mass were larger than 1 µm. The accuracy of nanoparticle collection by NRD diffusion stage may have been compromised by high concentrations of coarse particles at the iron foundry, where the NRD collected almost 5-fold more nanoparticle mass compared to the nanoMOUDI on one sampling day and was more than 40% different on other sampling days. The respirable concentrations measured by NRD samplers agreed well with concentrations measured by respirable samplers at all sampling locations. Overall, the NRD sampler accurately measured concentrations of nanoparticles in industrial environments when concentrations of large, coarse mode, particles were low.

Corticosteroid use endpoints in neuro-oncology: Response Assessment in Neuro-Oncology Working Group

Abstract

Background

Corticosteroids are the mainstay of treatment for peritumor edema but are often associated with significant side effects. Therapies that can reduce corticosteroid use would potentially be of significant benefit to patients. However, currently there are no standardized endpoints evaluating corticosteroid use in neuro-oncology clinical trials.

Methods

The Response Assessment in Neuro-Oncology (RANO) Working Group has developed consensus recommendations for endpoints evaluating corticosteroid use in clinical trials in both adults and children with brain tumors.

Results

Responders are defined as patients with a 50% reduction in total daily corticosteroid dose compared with baseline or reduction of the total daily dose to ≤2 mg of dexamethasone (or equivalent dose of other corticosteroid); baseline dose must be at least 4 mg of dexamethasone daily (or equivalent dose of other corticosteroids) for at least one week. Patients must have stable or improved Neurologic Assessment in Neuro-Oncology (NANO) score or Karnofsky performance status score or Eastern Cooperative Oncology Group (ECOG) (Lansky score for children age <16 y), and an improved score on a relevant clinical outcome assessment tool. These criteria must be sustained for at least 4 weeks after baseline assessment to be considered a response, and are confirmed 4 weeks after that (ie, 8 wk after baseline assessment) to be considered a sustained response.

Conclusions

This RANO proposal for corticosteroid use endpoints in neuro-oncology clinical trials may need to be refined and will require prospective validation in clinical studies.

Naïve realism: a simple approach

Abstract

Naïve realism is often characterized, by its proponents and detractors alike, as the view that for a subject to undergo a perceptual experience is for her to stand in a simple two-place acquaintance relation toward an object. However, two of the leading defenders of naïve realism, John Campbell and Bill Brewer, have thought it necessary to complicate this picture, claiming that a third relatum is needed to account for various possible differences between distinct visual experiences of the same object (for example, differences that result from changes in the object's spatial orientation relative to the subject, or from changes in the intensity with which the subject focuses her attention on the object). This, I argue, is a mistake. Once it is acknowledged that a subject's visual experience acquaints her with more than just a single object, all of the relevant facts can be explained from within the simpler naïve realist framework.

Influence of corticosteroid therapy on IL-18 and nitric oxide production during Behçet’s disease

Abstract

Background and aims

Behçet's disease (BD) is a chronic multisystemic inflammatory disease with complex etiopathogenesis. Th1-proinflammatory cytokines seem to be involved in its pathogenesis. Our current study aims to evaluate interleukin-18 (IL-18) and nitric oxide (NO) involvement in the development of different clinical manifestations of BD as well as to investigate the corticosteroid therapy effect on this production in Algerian patients.

Methods

For this purpose, we evaluated in vivo and ex vivo IL-18, interferon-γ (IFN-γ) levels using ELISA and NO production by the Griess' method in naïve-active and corticosteroid-treated BD patients with different clinical manifestations. Additionally, we assessed CD40/CD40L expression by flow cytometrics assay in these groups of patients.

Results and discussion

Our results indicate that IL-18 and nitrite levels were higher in naïve-active BD patients. Interestingly, this high production differed according to the clinical manifestations and was associated with an increased risk of mucocutaneous and vascular involvement. Concerning corticosteroid treated-active BD patients, no difference was observed in this production between each clinical subgroup. However, IFN-γ levels increased in all categories of active patients. Interestingly, corticosteroid therapy reduced significantly these inflammatory mediators regardless of the clinical manifestations studied. In addition, the CD40/CD40L expression differed according to the clinical presentations.

Conclusion

Collectively, our results suggest that concomitant high production of IL-18 and NO in naïve-active BD patients is related to an increased risk of mucocutaneous lesions and vascular involvement. Moreover, the relationship between these two inflammatory markers could constitute a predictable tool of BD clinical presentations and an early factor of therapy efficiency.

Oxidative stress as a possible mechanism of statin-induced myopathy

Abstract

Statins, inhibitors of hydroxy methyl glutaryl coenzyme-A (HMG-CoA) reductase, are the most widely used drugs for treating hypercholesterolemia. However, statins can cause disabling myopathy as their main adverse effect. Several molecular mechanisms underlie the statin-induced myopathy including the decrease in the levels of essential mevalonate and cholesterol derivatives. This review discusses a further mechanism involving the loss of other anti-oxidant defenses besides ubiquinone (Co-Q) in skeletal muscles which produce a significant amount of reactive oxygen species (ROS). Therefore, to maintain their function, skeletal muscles need a high level of anti-oxidants.

Enhancement of drug permeability across blood brain barrier using nanoparticles in meningitis

Abstract

The central nervous system, one of the most delicate microenvironments of the body, is protected by the blood–brain barrier regulating its homeostasis. Blood–brain barrier is a highly complex structure that tightly regulates the movement of ions of a limited number of small molecules and of an even more restricted number of macromolecules from the blood to the brain, protecting it from injuries and diseases. However, the blood–brain barrier also significantly precludes the delivery of drugs to the brain, thus, preventing the therapy of a number of neurological disorders. As a consequence, several strategies are currently being sought after to enhance the delivery of drugs across the blood–brain barrier. Within this review a brief description of the structural and physiological features of the barriers and the recently born strategy of brain drug delivery based on the use of nanoparticles are described. Finally, the future technological approaches are described. The strong efforts to allow the translation from preclinical to concrete clinical applications are worth the economic investments.

A Comparison of the United States and International Perspective on Chronic Urticaria Guidelines

Publication date: Available online 18 May 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Torsten Zuberbier, Jonathan A. Bernstein
Urticaria is a heterogeneous skin disorder that may be acute or chronic and is defined by the appearance of wheals, angioedema, or both. The European perspective is expressed in a recent international guideline and the American perspective has been based on the US Joint Task Force chronic urticaria practice parameter published in 2014. Both the international guideline (initiated by the European societies European Academy of Allergology and Clinical Immunology [EAACI]/Global Allergy and Asthma European Network [GA²LEN]/European Dermatology Forum [EDF] in collaboration with the World Allergy Organization [WAO]) and the US (American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology) guideline have been developed to help direct primary care physicians and specialists in the management of their patients with urticaria. The EAACI/GA²LEN/EDF/WAO guideline applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to developing consensus recommendations and these were then discussed in a Delphi conference including more than 250 specialists in the field and have been endorsed by more than 40 international societies. In contrast, the US Joint Task Force CU practice parameter made recommendations based on scientific evidence whenever possible; however, when there was insufficient evidence, recommendations were based on expert consensus opinion. Although both agree on most points regarding the definition, general evaluation, and treatment, there are some differences that exist between the 2 guidelines. Most of these differences pertain to recommendations based on expert opinion because of weak scientific evidence. Within this document, we compare the recommendations of these 2 groups, highlighting the key similarities and differences.