In This Issue

TcR-α recombinations in renal cell carcinoma exome files correlate with an intermediate level of T-cell exhaustion biomarkers

Abstract

Renal cell carcinoma exome-derived, V(D)J recombination reads had an elevated presence and variability, for both TcR-α and -β, when compared to marginal tissue, reflecting an opportunity to assess tumor immunogenicity by comparison with marginal tissue T cells. PD-1, PD-L2, CTLA4 and FOXP3, all of which are implicated in the evasion of an anti-tumor immune response, had a significantly higher expression for samples representing co-detection of productive TcR-α and -β recombination reads. Samples representing tumors with productive TcR-α recombination reads but no detectable, productive TcR-β recombination reads, reflected a 20% survival advantage, and RNASeq data indicated an intermediate level of immune checkpoint gene expression for those samples. These results raise the question of whether relatively high levels of detection of productive TcR-α recombination reads, in comparison with detection of reads representing the TcR-β gene, identify a microenvironment that has not yet entered a T-cell exhaustion phase and may thereby represent conditions for immune enhancements that do not require anti-immune checkpoint therapies.

Rapid immunosurveillance by recirculating lymphocytes in the rat intestine: critical role of unsulfated sialyl-Lewis X on high endothelial venules of the Peyer’s patches

Abstract

Naive lymphocytes systemically recirculate for immunosurveillance inspecting foreign antigens and pathogens in the body. Trafficking behavior such as the migration pathway and transit time within the gastrointestinal tract, however, remains to be elucidated. Rat thoracic duct lymphocytes (TDLs) were transferred to a congeneic host that had undergone mesenteric lymphadenectomy. The migration pathway was investigated using newly developed four-color immunohistochemistry and immunofluorescence. Donor TDLs showed rapid transition in gut tissues from which they emerged in mesenteric lymph around 4 h after intravenous injection. Immunohistochemistry showed that donor TDLs predominantly transmigrated across high endothelial venules (HEVs) at the interfollicular area of the Peyer's patches (PPs), then exited into the LYVE-1⁺ efferent lymphatics, that were close to the venules. The rapid recirculation depended largely on the local expression of unsulfated sialyl-Lewis X on these venules where putative dendritic cells (DCs) were associated underneath. Recruited naive T cells briefly made contact with resident DCs before exiting to the lymphatics in the steady state. In some transplant settings, however, the T cells retained contact with DCs and were sensitized and differentiated into activated T cells. In conclusion, we directly demonstrated that lymphocyte recirculation within the gut is a very rapid process. The interfollicular area of PPs functions as a strategically central site for rapid immunosurveillance where HEVs, efferent lymphatics and resident DCs converge. PPs can, however, generate alloreactive T cells, leading to exacerbation of graft-versus-host disease or gut allograft rejection.

Clinical response to PD-1 blockade correlates with a sub-fraction of peripheral central memory CD4+ T cells in patients with malignant melanoma

Abstract

Cancer immunotherapy that blocks immune checkpoint molecules, such as PD-1/PD-L1, unleashes dysfunctional antitumor T-cell responses and has durable clinical benefits in various types of cancers. Yet its clinical efficacy is limited to a small proportion of patients, highlighting the need for identifying biomarkers that can predict the clinical response by exploring antitumor responses crucial for tumor regression. Here, we explored comprehensive immune-cell responses associated with clinical benefits using PBMCs from patients with malignant melanoma treated with anti-PD-1 monoclonal antibody. Pre- and post-treatment samples were collected from two different cohorts (discovery set and validation set) and subjected to mass cytometry assays that measured the expression levels of 35 proteins. Screening by high dimensional clustering in the discovery set identified increases in three micro-clusters of CD4⁺ T cells, a subset of central memory CD4⁺ T cells harboring the CD27⁺FAS⁻CD45RA⁻CCR7⁺ phenotype, after treatment in long-term survivors, but not in non-responders. The same increase was also observed in clinical responders in the validation set. We propose that increases in this subset of central memory CD4⁺ T cells in peripheral blood can be potentially used as a predictor of clinical response to PD-1 blockade therapy in patients with malignant melanoma.

The immune checkpoint molecule VISTA regulates allergen-specific Th2-mediated immune responses

Abstract

V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a novel immune checkpoint receptor and ligand that regulates T-cell activation. We investigated the functional involvement of VISTA in T_h2 cell-mediated immune responses using an ovalbumin (OVA)-induced allergic asthma model. Treatment with an anti-VISTA monoclonal antibody (mAb) during allergen sensitization increased the production of antibodies, including total IgE, OVA-specific IgG1 and IgG2a and allergen-specific IL-5 and IL-13; it also increased the expression of IL-13 by splenic CD4⁺ T cells. However, treatment with the anti-VISTA mAb during sensitization did not accelerate asthmatic responses, including airway hyper-responsiveness (AHR) or the number of eosinophils in bronchoalveolar lavage (BAL) fluid. In contrast, treatment with the anti-VISTA mAb during allergen challenge significantly augmented AHR and BAL fluid eosinophilia. This treatment also increased the production of IL-5 and IL-13 in BAL fluid and the expression of IL-13 by CD4⁺ T cells in draining lymph nodes. These results suggest that VISTA is involved in the regulation of T_h2 cell generation and T_h2 cell-mediated antibody production and regulates asthmatic responses, especially in the effector phase.

Sweet syndrome associated with ipilimumab in a patient with metastatic melanoma

Use of a novel 1-hour protocol for rapid frozen section immunocytochemistry, in a case of squamous cell carcinoma treated with Mohs micrographic surgery

Summary

For squamous cell carcinoma (SCC) treated using Mohs micrographic surgery (MMS), interpretation of haematoxylin and eosin-stained frozen sections can be challenging. In these situations, ancillary use of immunostaining is a useful tool for the Mohs surgeon. However, use of immunostaining in MMS laboratories is limited, mainly because current manual immunostaining platforms are subject to operator error, and automated immunostaining, albeit accurate, is too slow for inclusion in MMS. In this report, we describe a novel 1-hour protocol for rapid frozen section immunocytochemistry, using the pancytokeratin markers AE1/AE3. This protocol has been specifically designed to integrate the speed of manual techniques and the accuracy of automated platforms, making it a valuable addition to the MMS laboratory. We propose that in selected or histologically challenging cases, there is a role for the use of this novel protocol, allowing the Mohs surgeon to more confidently declare tumour clearance, thus preventing further unnecessary surgery and preserving healthy tissue.

A new discussion of the cutaneous vascular reactivity in sensitive skin: A sub-group of SS?

Abstract

Background

Sensitive skin (SS) seems not to be a one-dimensional condition and many scholars concentrate on skin barrier disruption or sensorineural change, but few focus on its increased vascular reactivity. This study explored the possibility of using the different selection methods and measurement methods to verify a high vascular reactivity in SS without an impaired cutaneous barrier function.

Methods

Sixty "self-perceived sensitive skin" volunteers were enlisted and each one completed three kinds of screening tests: assess cutaneous sensory using questionnaire survey and Lactic Acid Sting Test (LAST); assess barrier function using Sodium lauryl sulphate (SLS) skin irritation test and assess cutaneous vascular reactivity using 98% DMSO test and non-invasive measurement. Volunteers were divided into different groups based on response to SLS. The DMSO clinical score and the biophysical parameters obtained by non-invasive measurement were subsequently analysed.

Results

(1) The positive correlations could be seen between sum LAST score and sum DMSO score regardless of the observation time; (2) The biological parameters (CBF、a*values and L* values) are all keeping with DMSO score; (3) If the participants were divided into SLS reactors and non-reactors, a composition ratio of DMSO score was significant difference in these two groups and in SLS non-reactors, there were still seven participants showed high reaction to DMSO.

Conclusions

There is a sub-group of SS for characteristics of a high vascular reactivity without an impaired cutaneous barrier function. The DMSO test and novel non-invasive measurements which are conducive to assess cutaneous vascular reactivity, combined with SLS skin irritation test could help us to screen this kind of SS.

An innovative method to quantitate tissue integration of hyaluronic acid-based dermal fillers

Abstract

Background/purpose

Following intradermal injection, hyaluronic acid (HA)-based fillers tend to spread within the reticular dermis and to distribute between the dermal fibers. This biointegration is commonly measured qualitatively using histological methods. We developed a "toolbox" consisting of a visual scoring and a semi-automatic image analysis method using internal developed algorithm to quantitate the biointegration of Restylane® in histological sections.

Methods

Restylane^® was injected intradermally in the abdominal skin of 10 healthy human subjects scheduled for abdominoplasty. The injections were performed either in vivo before surgery or ex vivo on samples taken post-surgery at different time points. The samples were processed for histology by visual scoring and image analysis using algorithms developed in Definiens to assess biointegration.

Results

The image analysis segmentation was accurate with <5% manual changes. Furthermore, the results calculated with the semi-automatic method were consistent with the visual scores obtained on injected human skin samples by means of a 5-grade photographic scale. A modified hematoxylin-eosin staining was found adequate to visualize both, the filler and the general morphology, on the same section. An excellent correlation was observed between the integration results obtained with PAS/Alcian Blue and HE-stained slides, allowing for a single staining in future studies.

Conclusion

We developed a modified HE staining histological method and a new histomorphometric image analysis tool to quantitate biointegration of HA-based fillers in human skin. The results obtained in this study confirmed the known intermediate biointegration properties of Restylane®, thus validating these innovative methods.

Value of a second dose of epinephrine during anaphylaxis: a patient/caregiver survey

Publication date: Available online 3 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): T. Ted Song, Duncan Brown, Martin Karjalainen, Ulrike Lehnigk, Phil Lieberman
BackgroundAnaphylaxis guidelines recommend prescription of >1 epinephrine auto-injector (EAI) for patients at risk. A second epinephrine dose is required in 16 to 36% of patients.ObjectiveEvaluate real-world use of EAIs and understand the patients/caregivers' adherence to guidelines.MethodsWe collected survey responses from United States patients and caregivers with an EAI prescription in November 2015. The survey covered several domains relevant to anaphylaxis and EAI use.ResultsThe survey was completed by 953 respondents (505 patients, 448 caregivers). Most respondents were women (71%). The majority of respondents had previously administered an EAI (75%). The mean age was 28 (standard deviation ± 14.0) years. 786 (82%) respondents did not carry 2 EAIs all the time, and the main reason given was to keep 1 EAI in another location. Most respondents kept at least 1 EAI at home (84%). The percentages of respondents with >1 EAI available at locations surveyed were low (patients: 22% at home, 2% at work; caregivers: 27% at home, 10% at school). During training most respondents (64%) were instructed to always carry 1 EAI and keep the other in another location. Half of the respondents reported the use of a second epinephrine dose in a previous event. 45% of the 73 respondents who sought emergency care did so because of the unavailability of a second dose.ConclusionOur study suggests poor adherence in patients and caregivers to anaphylaxis guidelines recommending >1 EAI available at all times and implies that this can result in adverse outcomes.

Cross-Reactivity and Tolerability Of Cephalosporins In Patients With Ige-Mediated Hypersensitivity To Penicillins

Publication date: Available online 3 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Antonino Romano, Rocco Luigi Valluzzi, Cristiano Caruso, Michela Maggioletti, Donato Quaratino, Francesco Gaeta
BackgroundStudies performed since 1990 on samples of at least 30 subjects with a documented IgE-mediated hypersensitivity to penicillins have found a rate of positive responses to allergy tests with cephalosporins ranging from 0% to 27%.ObjectiveWe sought to assess the cross-reactivity with cephalosporins and evaluate the possibility of using cephalosporins in penicillin-allergic subjects.MethodWe conducted a prospective study of 252 consecutive subjects who had suffered 319 immediate reactions (mostly anaphylaxis) to penicillins and had positive skin tests to at least one penicillin reagent.All patients underwent serum specific IgE assays for cefaclor, as well as skin tests with 3 aminocephalosporins (cephalexin, cefaclor, and cefadroxil), cefamandole, cefuroxime, ceftazidime, ceftriaxone, cefotaxime, and cefepime. Patients with negative results for the last 5 cephalosporins were challenged with cefuroxime axetil and ceftriaxone; those with negative results for aminocephalosporins were also challenged with cefaclor and cefadroxil.ResultsNinety-nine participants (39.3%) had positive allergy tests for cephalosporins. Specifically, 95 (37.7%) were positive to aminocephalosporins and/or cefamandole, which share similar or identical side chains with penicillins.All 244 subjects who underwent challenges with cefuroxime axetil and ceftriaxone tolerated them. Of the 170 patients who underwent aminocephalosporin challenges, 3 reacted to cefaclor and 4 to cefadroxil.ConclusionsCross-reactivity between penicillins and cephalosporins seems to be mainly related to side chain similarity or identity.Subjects with an IgE-mediated hypersensitivity to penicillins could be treated with cephalosporins like cefuroxime and ceftriaxone that have side chain determinants different from those of penicillins and are negative in pretreatment skin testing.

Inhaled corticosteroids safety and adverse effects in patients with asthma

Publication date: Available online 3 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Enrico Heffler, Lorena Nascimento Girardi Madeira, Matteo Ferrando, Francesca Puggioni, Francesca Racca, Luca Malvezzi, Gianni Passalacqua, Giorgio Walter Canonica
Asthma is a common inflammatory airway disease for which the most commonly used controller medications are inhaled corticosteroids (ICS). Asthma control is difficult to achieve in individuals with severe asthma, which comprise 5-10% of individuals with asthma, even with high doses of ICS and other anti-inflammatory drugs.In this clinical context, the adverse effects of ICS (including hypothalamic-pituitary-adrenal axis suppression, reduction in growth velocity, osteoporosis, diabetes, and respiratory infections) become more probable and impacting on the quality of life of severe asthmatics. We here summarize the evidence of ICS-related adverse effects, particularly in patients with asthma. The possibility to use biologic agents earlier for severe asthma has the potential to prevent or reduce the occurrence of corticosteroid-related adverse effects, and also reduce corticosteroid-related costs.

Tiotropium attenuates refractory cough and capsaicin cough reflex sensitivity in patients with asthma

Publication date: Available online 3 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Kensuke Fukumitsu, Yoshihiro Kanemitsu, Takamitsu Asano, Norihisa Takeda, Hiroya Ichikawa, Jennifer Maries Go Yap, Satohi Fukuda, Takehiro Uemura, Osamu Takakuwa, Hirotsugu Ohkubo, Ken Maeno, Yutaka Ito, Tetsuya Oguri, Atsushi Nakamura, Masaya Takemura, Akio Niimi
BackgroundAsthmatic cough is often refractory to standard treatments such as inhaled corticosteroids and long-acting β2 agonists (ICS/LABA). Tiotropium may modulate cough reflex sensitivity of acute viral cough, but its efficacy in asthmatic cough remains unknown.ObjectiveTo evaluate whether tiotropium improves cough and cough reflex sensitivity in asthmatic patients refractory to ICS/LABA.MethodsSeventeen consecutive asthmatic patients with chronic cough despite the use of ICS/LABA [13 females; 43.4 (19.0) years-old; average ICS dose 651 (189) μg/day, fluticasone equivalent] were additionally treated with tiotropium (5 μg/day) for 4 to 8 weeks to examine its effects on pulmonary function and capsaicin cough reflex sensitivity (cough thresholds; C2 and C5). Cough severity, cough-specific quality of life, and asthma control were also evaluated using cough visual analog scales (VAS), the Japanese version of Leicester Cough Questionnaire (J-LCQ), and Asthma Control Test (ACT), respectively. Patients with an improved cough VAS of ≥15 mm were considered responders to tiotropium.ResultsTiotropium significantly improved cough VAS, J-LCQ, and ACT scores, but not forced expiratory volume in 1 second (FEV1). Changes in cough VAS correlated with those in C2 (r=-0.58, p=0.03), C5 (r=-0.58, p=0.03), and ACT scores (r=-0.62, p=0.02), but not in FEV1 in the overall patients. When analyses were confined to the 11 responders, tiotropium significantly improved capsaicin cough reflex sensitivity within the subgroup (C2: p=0.01 and C5: p=0.02), and versus the non-responders (C2: p=0.004 and C5: p=0.02).ConclusionTiotropium may alleviate asthmatic cough refractory to ICS/LABA by modulating cough reflex sensitivity but not thorough bronchodilation.

Partial RAG Deficiency in a Patient with Varicella Infection, Autoimmune Cytopenia, and Anti-Cytokine Antibodies

Publication date: Available online 2 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Vera Goda, Aniko Malik, Tibor Kalmar, Zoltan Maroti, Bhumika Patel, Boglarka Ujhaz, Krisztian Csomos, Jaime E. Hale, Karin Chen, Jacob Bleesing, Paolo Palma, Caterina Cancrini, Anne M. Comeau, Gergely Krivan, Jolan E. Walter

Clinician Agreement, Self-efficacy, and Adherence with the Guidelines for the Diagnosis and Management of Asthma

Publication date: Available online 3 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Michelle M. Cloutier, Paivi M. Salo, Lara J. Akinbami, Richard D. Cohn, Jesse C. Wilkerson, Gregory B. Diette, Sonja Williams, Kurtis S. Elward, Jacek M. Mazurek, Jovonni R. Spinner, Tracey A. Mitchell, Darryl C. Zeldin
BackgroundThe 2007 Guidelines for the Diagnosis and Management of Asthma provide evidence-based recommendations to improve asthma care. Limited national-level data are available about clinician agreement and adherence to these guidelines.ObjectiveTo assess clinician-reported adherence with specific guideline recommendations, as well as agreement with and self-efficacy to implement guidelinesMethodsWe analyzed 2012 National Asthma Survey of Physicians data for 1412 primary care clinicians and 233 asthma specialists about four cornerstone guideline domains: asthma control, patient education, environmental control, and pharmacologic treatment. Agreement and self-efficacy were measured using Likert scales; two overall indices of agreement and self-efficacy were compiled. Adherence was compared between primary care clinicians and asthma specialists. Logistic regression models assessed the association of agreement and self-efficacy indices with adherence.ResultsAsthma specialists expressed stronger agreement, higher self-efficacy, and greater adherence with guideline recommendations than primary care clinicians. Adherence was low among both groups for specific core recommendations, including written asthma action plan (30.6% and 16.4%, respectively P<.001); home peak flow monitoring, (12.8% and 11.2%, P=.34); spirometry testing, (44.7% and 10.8%, P<.001); and repeated assessment of inhaler technique, (39.7% and 16.8%, P<.001). Among primary care clinicians, greater self-efficacy was associated with greater adherence. For specialists, self-efficacy was associated only with increased odds of spirometry testing. Guideline agreement was generally not associated with adherence.ConclusionsAgreement with and adherence to asthma guidelines was higher for specialists than primary care clinicians, but was low in both groups for several key recommendations. Self-efficacy was a good predictor of guideline adherence among primary care clinicians but not among specialists.

As You Eat It: Effects of prenatal nutrition on asthma

Publication date: Available online 2 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Kathleen Lee-Sarwar, Augusto A. Litonjua
Asthma most frequently develops early in life, and increased recognition of the role of lifestyle and environmental factors in asthma susceptibility raises the possibility that dietary exposures during pregnancy may influence risk of asthma in offspring. This review discusses the latest evidence with regard to the effect of diet during pregnancy on childhood asthma risk, including potential mechanisms, outcomes of randomized clinical trials, and results from observational studies. Vitamin D and polyunsaturated fatty acid intake during pregnancy are highlighted as areas with large and growing bodies of literature to support a potential role in prenatal modulation of subsequent asthma risk. Several other nutritional interventions are under active investigation, and recommendations regarding dietary modifications during pregnancy will likely need to be personalized based on factors such as maternal smoking and genetic variants. Though nutrition during pregnancy is uniquely challenging to investigate, and definitive recommendations cannot be made without additional high quality evidence and knowledge regarding long-term effects of interventions, the modifiable nature of the diet and sizeable potential reduction of morbidity supports ongoing research to determine how to optimize nutrition during pregnancy to prevent asthma in offspring.

Two-week intervals during omalizumab treatment may provide better symptom control in selected patients with chronic urticaria

Publication date: Available online 2 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Murat Türk, Emek Kocatürk, Kübra Cüre, İnsu Yılmaz

Ara h 2 basophil activation test does not predict clinical reactivity to peanut

Publication date: Available online 2 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Alexandra Chapuis, Jonathan Thevenot, Frédéric Coutant, Khaled Messaoudi, Elodie Michaud, Bruno Pereira, Emmanuelle Rochette, Nelly Gourdon-Dubois, Etienne Merlin, Jean-Luc Fauquert, Bertrand Evrard, Paul Rouzaire

Male X-chromosome Mosaicism leading to Carrier Phenotype and inheritance of Chronic Granulomatous Disease

Publication date: Available online 2 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Stephanie Harris, Helen Braggins, Karin van Leeuwen, Kimberly Gilmour, Matthew S. Buckland, Dirk Roos, David M. Lowe

Determination of the Preferred Tongue Position for Optimal Inhaler Use

Publication date: Available online 2 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Takahiko Horiguchi, Rieko Kondo

Soluble delta-like 1 homolog (DLK1) stimulates angiogenesis through Notch1/Akt/eNOS signaling in endothelial cells

Abstract

Aim

Delta-like 1 homolog (DLK1) is a non-canonical ligand of Notch signaling, which plays a pivotal role in vascular development and tumor angiogenesis. This study aimed to elucidate the function and mechanism of DLK1 in angiogenesis.

Methods and results

By using in situ hybridization and immunohistochemical studies, expression analysis revealed a unique vascular tropism of DLK1 in vasculature of neuroblastoma and vascular tumors. Thus, it was hypothesized that DLK1 may be cleaved and then bound to endothelial cells, thereby regulating the endothelial function. To test such hypothesis, soluble DLK1 encompassing DLK1 extracellular domain (DLK1-EC) was generated and validated by its inhibitory function in adipogenesis assay. Recombinant DLK1-EC exhibited the preferential binding capability toward endothelial cells and stimulated the microvessels sprouting in aorta rings. Above all, implantation of DLK1-EC dose-dependently elicited the cornea neovascularization in rats. By using various angiogenesis assays, it was delineated that DLK1-EC stimulated the angiogenesis by promoting the proliferation, motility and tube formation of endothelial cells. By immunoblot and luciferase analysis, it was elucidated that DLK1-EC enhanced the expression and activities of Notch1/Akt/eNOS/Hes-1 signaling in dose- and time-dependent manners. Pharmaceutical blockage of Notch signaling using γ-secretase inhibitor DAPT abrogated the DLK1-EC-induced endothelial migration and Hes-1-driven luciferase activities. Furthermore, Notch1 inactivation by neutralizing antibodies or RNA interference reversed the DLK1-EC-induced angiogenesis.

Conclusions

The present study unveils the pro-angiogenic function and mechanism of soluble DLK1 through activation of Notch1 signaling in endothelial cells.

miRNAs regulate the HIF switch during hypoxia: a novel therapeutic target

Abstract

The decline of oxygen tension in the tissues below the physiological demand leads to the hypoxic adaptive response. This physiological consequence enables cells to recover from this cellular insult. Understanding the cellular pathways that mediate recovery from hypoxia is therefore critical for developing novel therapeutic approaches for cardiovascular diseases and cancer. The master regulators of oxygen homeostasis that control angiogenesis during hypoxia are hypoxia-inducible factors (HIFs). HIF-1 and HIF-2 function as transcriptional regulators and have both unique and overlapping target genes, whereas the role of HIF-3 is less clear. HIF-1 governs the acute adaptation to hypoxia, whereas HIF-2 and HIF-3 expressions begin during chronic hypoxia in human endothelium. When HIF-1 levels decline, HIF-2 and HIF-3 increase. This switch from HIF-1 to HIF-2 and HIF-3 signaling is required in order to adapt the endothelium to prolonged hypoxia. During prolonged hypoxia, the HIF-1 levels and activity are reduced, despite the lack of oxygen-dependent protein degradation. Although numerous protein factors have been proposed to modulate the HIF pathways, their application for HIF-targeted therapy is rather limited. Recently, the miRNAs that endogenously regulate gene expression via the RNA interference (RNAi) pathway have been shown to play critical roles in the hypoxia response pathways. Furthermore, these classes of RNAs provide therapeutic possibilities to selectively target HIFs and thus modulate the HIF switch. Here, we review the significance of the microRNAs on the relationship between the HIFs under both physiological and pathophysiological conditions.

A population genetics analysis in clinical isolates of Sporothrix schenckii based on calmodulin and calcium/calmodulin-dependent kinase partial gene sequences

Summary

Background

Sporotrichosis is a subcutaneous mycosis that is caused by diverse species of Sporothrix. High levels of genetic diversity in Sporothrix isolates have been reported, but few population genetics analyses have been documented.

Aim

To analyze the genetic variability and population genetics relations of Sporothrix schenckii Mexican clinical isolates and to compare them with other reported isolates.

Methods

We studied the partial sequences of calmodulin and calcium/calmodulin-dependent kinase genes in 24 isolates; 22 from Mexico, one fromColombia, and one ATCC^®6331^™; the latter was used as a positive control. In total, 24 isolates were analyzed. Phylogenetic, haplotype and population genetic analyses were performed with 24 sequences obtained by us and 345 sequences obtained from GenBank.

Results and conclusions

The frequency of Sporothrix schenckii sensu stricto was 81% in the 22 Mexican isolates, while the remaining 19% were Sporothrix globosa. Mexican S. schenckii sensu stricto had high genetic diversity and was related to isolates from South America. In contrast, S. globosa showed one haplotype related to isolates from Asia, Brazil, Spain and the USA. In S. schenckii sensu stricto, S. brasiliensis and S. globosa, haplotype polymorphism (θ) values were higher than the nucleotide diversity data (π). Additionally, Tajima′s D plus Fu and Li′s tests analyses displayed negative values, suggesting directional selection and arguing against the model of neutral evolution in these populations. In addition, analyses showed that calcium/calmodulin-dependent kinase was a suitable genetic marker to discriminate between common Sporothrix species.

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Dupilumab treatment in moderate-to-severe atopic dermatitis: A systematic review and meta-analysis

Atopic dermatitis (AD) is a common chronic skin condition with a worldwide prevalence of 1 to 20% in adults, approximately 20% of patients have moderate-to-severe disease [1–4]. It is characterized by the T-helper (Th)-2-mediated skin inflammation, epidermal barrier dysfunction and increased Staphylococcus aureus colonization [5,6]. Despite the high prevalence of AD, treatments are limited, especially for patients with moderate to severe disease, only 3 (depending on country) systemic therapeutic options approved for patients with severe disease who are not controlled by topical medications, including oral corticosteroids, oral cyclosporin, and UVA/narrow-band UVB phototherapy [7].

Reduced-HMGB1 suppresses poly(I:C)-induced inflammation in keratinocytes

HMGB1 was originally characterized as a non-histone chromosomal protein constitutively expressed in mammalian cells that contributes to various aspects of nuclear homeostasis, such as stabilization of nucleosomes, DNA repair and recombination, and transcription [1,2]. Recent reports showed that HMGB1 also has cytokine-like properties and can induce inflammatory responses via its interaction with cell surface-expressed innate receptors [1,3–6]. Two different routes of HMGB1 release have been reported.

The Headache-Attributed Lost Time (HALT) Indices: measures of burden for clinical management and population-based research

The burden attributable to headache disorders has multiple components: a simple measure summarising them all does not exist. The Migraine Disability Assessment (MIDAS) instrument has proved useful, estimating ...

Response to: Studying the blood pressures of antegrade and retrograde internal mammary vessels: Do they really work as recipient vessels? Tomioka YK, Uda H, Yoshimura K, Sunaga A, Kamochi H, Sugawara Y. J Plast Reconstr Aesthet Surg. 2017 Oct;70(10):1391-1396.

We congratulate Tomioka et al. on an interesting article assessing intraoperatively the arterial and venous pressures in both the antegrade and retrograde limbs of the internal mammary vessels.1 The authors report positively on the recorded arterial and venous pressures in the retrograde vessels, demonstrating clearly that in their series of ten free flap breast reconstructions, there is adequate arterial flow and sufficiently low venous back pressure to allow perfusion of a second microsurgery recipient site.

The pedicled internal pudendal artery perforator flap for ischial pressure sore reconstruction: technique and long-term outcome of a cohort study

The ischial region is the site most affected by pressure sores and has the highest recurrence and complication rates compared to other affected sites. We developed a practical and safe pedicled flap for reconstruction of ischial pressure sores based on the rich available perforators from the internal pudendal artery and the surplus of skin at the infragluteal fold.

Upgrading the BREAST-Q questionnaire with donor site evaluation after PAP flap breast reconstruction.

Dear Sir:

The ‘wifi’ otoplasty : combined concentric posterior microchondrectomies and sutures for correction of prominent ears

Prominent ears are by far the most common congenital ear deformity. Many techniques have been described using one or a combination of 3 basic methods: cartilage cutting, cartilage weakening and pure cartilage shaping techniques. The ideal otoplasty technique should yield a natural correction of the deformity, with low recurrence rates and with little risk of complications.

Reduction of the DIEP flap donor site morbidity through a minimally invasive pedicle harvest with jacob's ladder incisions.

Despite the decrease of donor-site morbidity through the introduction of the deep inferior epigastric artery perforator (DIEP) flap as successor of the free transverse rectus abdominis (TRAM) flap, abdominal complications still occur. The etiology of lower abdominal bulging following breast reconstruction with the DIEP flap is still under debate. Most studies estimate the incidence for a postoperative lower abdominal bulging to be between 0.7% and 5%. However, a higher number of undetected and unreported cases is not unusual.

Time course of improvement after re-repair procedure for VPI management

Palatal re-repair aims to improve velar function by retro-positioning the levator veli palatini muscles. The surgery includes extensive dissection, leading to tissue edema and scar formation which may need time to remodel. Together with the change of muscle orientation and tension, it is expected that a period of time is needed to reach the final functional performance. This study attempts to determine how much time is required to reach the optimum performance of the palate after re-repair.

‘Abdominal reanimation’ and massive flank hernias: moving towards a more functional reconstruction

Dear Sir,

The impact of a career night information session on medical students' perceptions of the scope of practice of plastic surgeons

- Misconceptions surrounding the scope of practice of plastic surgeons are common amongst health care professionals. Medical students are vulnerable to these misconceptions. The aim of this study is to assess the impact of an information event on medical students with respect to their interest and knowledge of the scope of practice of plastic surgeons.

An analysis of the breast reduction mammaplasty research pipeline

It has been more than 6 years since the American Society of Plastic Surgeon's (ASPS) reduction mammaplasty guideline was published, and therefore, it may be out of date with current literature. Evidence suggests that recommendations quickly become outdated, as 20% of recommendations may become out of date after 3 years.1 It may be necessary for the ASPS to consider an update of this current guideline. However, until a guideline update is published, researchers may be unaware of the extent of new and ongoing reduction mammaplasty research.

Free second dorsal metacarpal artery flap for digital reconstruction: when you cannot go local, you can go free

Traditionally flaps based on the dorsal metacarpal artery system are used as pedicled or islanded flaps to cover defects on the dorsum of the hand or digits. In these areas they provide like for like tissues in texture, colour and quality to skin over the digits. 1, 2, 3.

Breast reconstruction and risk of arm lymphedema development: a meta-analysis breast

Lymphedema remains a significant complication following breast cancer surgery when there is axillary lymph node intervention. Previous systematic reviews have identified risk factors for breast cancer-related lymphedema, including increased BMI, number of lymph nodes dissected and radiotherapy. However, they have not examined the effect of breast reconstruction on lymphedema occurrence. In this systematic review and meta-analysis, we sought to evaluate the association between Breast Reconstruction (BR) and lymphedema.

Anatomical relationship of the right internal jugular vein and the spinal accessory nerve – a word of caution.

We wish to report an usual relationship between the internal jugular vein and the spinal accessory nerve. We highlight this as a word of caution to head and neck surgeons performing neck dissections, so that they are aware of this anomalous relationship in an effort to prevent iatrogenic injury.

Time to re-group and save: do we routinely need to perform group-and-save in patients undergoing free deep inferior epigastric perforator (DIEP) flap breast reconstruction?

Dear Sir,

“Current evidence on the role of smoking in plastic surgery elective procedures: a systematic review and meta-analysis.”

Smoking is considered to be a significant risk factor for the development of postoperative complications after various surgical procedures, mainly by limiting oxygen delivery to tissues. Evidence on the collective impact of smoking in aesthetic procedure outcomes is scarce. The aim of this study is to evaluate the current evidence on the association between smoking and postoperative outcomes in patients who underwent common elective procedures in plastic surgery.

Distally based anteromedial thigh flaps pedicled on the rectus femoris branch of the lateral circumflex femoral artery for reconstruction of soft-tissue defect of the knee

Anteromedial thigh flaps are far less clinically appealing than their anterolateral counterparts, and are occasionally considered as an alternative to the anterolateral thigh flap. Herein, we report the study of soft-tissue defects reconstruction in the knee using a distally based anteromedial thigh flap pedicled on the rectus femoris branch of the descending branch of the lateral circumflex femoral artery.Patients and Methods: Between July 2008 and September 2016, a distally based anteromedial thigh flap was used to reconstruct soft-tissue defects of the knee in 5 patients (3 males, 2 females; age range at surgery 4–55 years old).

Intralesional cryotherapy versus excision with corticosteroid injections or brachytherapy for keloid treatment: randomised controlled trials.

Keloids are a burden for patients due to physical, aesthetic and social consequences. Treatment remains a challenge due to therapy resistance and high recurrence rates. The main goals of treatment are to improve scar appearance and symptoms and patients' quality of life (QoL).

The use of SERI™ surgical scaffolds in direct-to-implant reconstruction after skin-sparing mastectomy: a retrospective study on surgical outcomes and a systematic review of current literature.

Little is reported on surgical outcomes of SERI Surgical Scaffold, a bioresorbable silk-derived surgical scaffold, developed to provide soft-tissue support and repair, in implant/expander breast reconstruction.

A Systematic Review and Meta-Analysis of the Effects of Topical Nitrates in the Treatment of Primary and Secondary Raynaud’s Phenomenon

Multiple placebo controlled trials have assessed locally applied topical nitrate preparations in treating Raynaud's phenomenon (RP).

Diacerein Orphan Drug Development for Epidermolysis Bullosa Simplex: A Phase 2/3 Randomized, Placebo-Controlled, Double-Blind Clinical Trial

EBS is a rare genetic, blistering skin disease for which there is no cure. Treatments that address the pathophysiology of EBS are needed.

Baricitinib in adult patients with moderate-to-severe atopic dermatitis: a phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study

Baricitinib, an oral selective inhibitor of Janus kinase (JAK)1 and JAK2, modulates pro-inflammatory cytokine signaling.

UV modification of biochar for enhanced hexavalent chromium removal from aqueous solution

Abstract

This study was conducted to understand the effects of ultraviolet (UV) irradiation on the physicochemical properties and the hexavalent chromium (Cr(VI)) removal ability of biochar. Structural and morphological analysis showed that UV irradiation increased the specific surface area of biochar and added a large amount of oxygen-containing functional groups (e.g., carboxyl, lactonic, and hydroxyl) to biochar's surface. Batch sorption experimental results showed that UV-modified biochar (UVBC) produced at the pyrolysis temperature of 300 °C, the irradiated time of 24 h, and the irradiation distance of 40 mm exhibited excellent Cr(VI) removal ability (from 1.11 mg/g for BC to 20.04 mg/g for UVBC, a 18.1-fold increase). The adsorption kinetics and adsorption isotherm data agreed well with the pseudo-second-order model and Freundlich model, respectively. Experimental and modeling results suggest that the oxygen-containing functional groups and specific surface areas of biochars were notably increased by UV irradiation, which enhanced Cr(VI) adsorption by surface complexation. X-ray photoelectron spectroscopy (XPS) analysis of UVBC before and after reaction with Cr(VI) showed that reduction occurred during Cr(VI) adsorption. The energy consumption of UV modification is 2.7 MJ per gram of UVBC produced, which is comparable to that in activated carbon. The results showed that the method of UV modification of biochar is a very novel and effective method for the adsorption of Cr(VI) in solution.

Sorption of pentachlorophenol (PCP) in the marine bottom sediments—batch sorption experiment at varying pressure

Abstract

Study was undertaken to determine the effect of hydrostatic pressure on the sorption of pentachlorophenol (PCP). The experiment was conducted at atmospheric pressure (1000 hPa) and at increased pressure (6000 hPa) simulating conditions at the water depth of 50 m. The sorption of PCP was examined in an artificial environment (microcosm) consisting of the marine water and the bottom sediments from a Polish harbor and the southern Baltic Sea. The first part of the experiment comprised the determination of PCP sorption parameters in the microcosms and parameters of the sediments (organic matter content, conductivity) and of the overlying water (pH, ion concentration) at 1000 hPa. The second part of the experiment was conducted at 6000 hPa inside the hyperbaric chamber. The hyperbaric exposure affected parameters of the harbor sediments and the overlying water but had little influence on the concentration of PCP in the microcosms containing the southern Baltic Sea sediments. Considering the specific characteristics of the harbor sediments, it can be assumed that the impact of hydrostatic pressure on the sorption process of PCP at 50-m depth appears to be negligible.

Precis for Responsibility from the Margins

Model-theoretic semantics and revenge paradoxes

Abstract

Revenge arguments purport to show that any proposed solution to the semantic paradoxes generates new paradoxes that prove that solution to be inadequate. In this paper, I focus on revenge arguments that employ the model-theoretic semantics of a target theory and I argue, contra the current revenge-theoretic wisdom, that they can constitute genuine expressive limitations. I consider the anti-revenge strategy elaborated by Field (J Philos Log 32:139–177, 2003; Revenge of the Liar, Oxford University Press, Oxford, pp 53–144, 2007; Saving truth from paradox, Oxford University Press, Oxford, 2008, §§21–23) and argue that it does not offer a way out of the revenge problem. More generally, I argue that the difference between 'standard' and 'revenge' paradoxes is ill-conceived and should be abandoned. This will contribute to show that the theories that provide a uniform account of truth and other semantic notions are the ones best equipped to avoid the paradoxes altogether—'standard' and 'revenge' alike.

Impact of humic acid on the accumulation of metals by microalgae

Abstract

Indirect impact of humic acid (HA) on metal accumulation and toxicity (Cd, Ni, Pb, and Hg; 100 μM; 24 h of exposure) in Scenedesmus quadricauda was studied. Algae were pre-cultured on solid (10 and 100 mg HA/L) or in liquid media (1, 5, and 10 mg HA/L) over 30 days and then exposed to metals mentioned above. Accumulation of applied metals irrespective of pre-culture increased in the order Ni < Cd < Pb < Hg. Algae pre-cultured on solid HA-enriched media accumulated more Cd (+ 46% at 10 mg HA/L), Ni (+ 50 and + 81% at 10 and 100 mg HA/L, respectively), and Pb (+ 15% at 100 mg HA/L) but the impact on Hg amount was not detected. Potassium and calcium decreased in response to all metals (K strongly under Hg excess) and HA had negligible impact. Interestingly, fluorescence microscopy detection of reactive oxygen species/nitric oxide (ROS/NO) balance showed that HA pre-culture suppressed ROS signal and stimulated NO signal in response to Cd (indicating positive impact of HA) while ROS signal in Ni and Pb treatments rather increased but NO signal decreased as expected from elevated Ni and Pb accumulation. Hg had clearly the most toxic impact on the ROS/NO balance. Algae pre-cultured in liquid HA-enriched media showed significantly increased Ni accumulation only (+ 14% at a dose 10 mg HA/L). Present study for the first time showed that humic acid may indirectly affect accumulation of metals and that solid HA-enriched medium used for pre-culture is more suitable to increase accumulation of metals by algae.

Cilostazol induced migraine does not respond to sumatriptan in a double blind trial

Cilostazol is an inhibitor of phosphodiesterase 3 and thus causes accumulation of cAMP. It induces migraine-like attacks in migraine patients. Whether the cilostazol model responds to sumatriptan in migraine p...

Performance of A 2 NO-MBR process in treating synthetic and municipal wastewater

Abstract

In this study, a novel anaerobic-anoxic/nitrification (A₂N) two-sludge sequencing batch reactor (SBR) configured with post-aeration (A₂NO-membrane bioreactor process) was conducted to evaluate the operational efficiency, process characteristics, and microbial community structure in treating synthetic and municipal wastewater. When influent C/N ratios were 4.2–8.6, the removal efficiencies of COD, NH₄⁺-N, TN, and TP were 86.4–90.0, 85.2–93.6, 61.8–76.0, and 97.6–99.3%, respectively, and the effluent concentrations met the first level A criteria of GB18918-2002. Phosphorus removal was mainly in anoxic phase with a removal rate of 0.54–1.30 mgP/(gMLSS h), accounting for 75.9–99.7%. Enhanced phosphorus removal was observed during post-aeration phase with a removal rate of 0.06–0.55 mgP/(gMLSS h). Additionally, Oxidation-Reduction Potential (ORP) and pH could reflect the process of anaerobic phosphorus release and anoxic denitrifying phosphorus removal. DO and pH could indicate the end of nitrification. Moreover, Candidatus Accumulibacter and Dechloromonas related to biological nitrogen and phosphorus removal were enriched effectively with total proportions of 15.9 and 11.5% in treating synthetic and municipal wastewater, respectively.

Hu antigen R (HuR) heterogeneous expression quantification as a prognostic marker of melanoma

Abstract

Background

Prognostic markers for melanoma, particularly for stage II disease, are needed for the risk benefit evaluation of future adjuvant therapies. The mainly nuclear RNA-binding protein HuR regulates the protein expression of thousands of mRNAs, its own heterogeneous expression could therefore reflect tumor heterogeneity and plasticity. Here, we evaluate its quantification in primary melanoma as a marker of metastatic outcome.

Methods

We conducted an immunohistochemistry-based automated quantification of HuR nuclear expression heterogeneity in primary melanomas most with Breslow thickness ≥ 1 mm and calculated the dimensionless fourth moment, i.e. the Kurtosis of HuR (HuR K) expression distribution. 12 tumors from patients with no metastatic disease were compared to a similar number of tumors from patients who had metastatic disease at two years follow-up.

Results

HuR K value, appeared significantly higher in the non-metastatic group comparatively to the metastatic group (P=2.84 × 10⁻³, one-tail Wilcoxon rank-sum test). Moreover, compared to the Breslow thickness, HuR K value appeared as a more robust marker of metastatic outcome (respective areas under ROC curves 0.84 and 0.87).

Conclusion

Our data need confirmation on a large cohort, however strongly suggest that HuR expression heterogeneity quantification using kurtosis, could be used as a prognostic marker in melanoma.

Mg2+ Reduces Biofilm Quantity in Acidithiobacillus ferrooxidans through inhibiting Type IV Pili Formation

Abstract

Bioleaching is a promising process for 350 million tons Jinchuan low grade pentlandite. But high concentration of Mg²⁺ is harmful to bioleaching microorganisms. Interestingly, biofilm formation can improve leaching rate. Thus, it is actual necessary to investigate the effect of Mg²⁺ stress on Acidithiobacillus ferrooxidans biofilms formatiom. In this study, we found that 0.1 and 0.5M Mg²⁺ stress significantly reduced the total biomass of biofilm in a dose-dependent manner. The observation results of EPS and bacteria using Confocal Laser Scanning Microscopy showed the biofilm became thinner and looser under Mg²⁺ stress. Whereas, 0.1 and 0.5M Mg²⁺ stress had no remarkable effect on the bacterial viability. The attachment rate of Acidithiobacillus ferrooxidans to pentlandite was reduced by Mg²⁺ stress. Furthermore, Sliding motility, twitching motility and the gene expression level of pilV and pilW were inhibited under Mg²⁺ stress. These results suggested Mg²⁺ reduced biofilm formation through inhibiting pilV and pilW gene expression, decreasing Type IV pili formation, and then attenuating the ability of attachment, subduing the active expansion of biofilms mediated by twitching motility. This study provided more information about the effect of Mg²⁺ stress on biofilm formation and may be useful for increasing the leaching rate in low grade pentlandit.

Issue Information

Human lactoferrin attenuates the proinflammatory response of neonatal monocyte-derived macrophages

Abstract

Bioactive components of human milk such as human lactoferrin (hLF) play an essential role in gut microbiome homeostasis and protection against neonatal inflammatory diseases. Neonatal intestinal macrophages display a pro-inflammatory profile that might contribute to inflammatory mucosal injury. Therefore, the aim of the study was to investigate the immunomodulatory effects of hLF on differentiation and activation of monocyte-derived macrophages (moMϕ). Monocytes isolated from umbilical cord blood of term neonates and peripheral blood of healthy adults were differentiated in the absence or presence of hLF and differentiation, apoptosis and phagocytosis were evaluated. Cytokine production, toll like receptor (TLR) signaling and activation marker expression were investigated upon activation with LPS and LTA challenge. We demonstrate that hLF-differentiated moMϕ exhibit decreased TLR4 expression, TLR signaling, proinflammatory cytokine secretion and intracellular TNFα production. Investigation of differentiation markers, morphology and induction of apoptosis showed no alteration in lactoferrin-differentiated moMϕ. Taken together, hLF promote anergic/anti-inflammatory effects by TLR expression and pathway interference resulting in a diminished pro-inflammatory moMϕ phenotype. The anergic/anti-inflammatory properties of hLF might contribute to the prevention of harmful TLR-mediated inflammatory disorders in the developing gut of premature infants. This article is protected by copyright. All rights reserved.

The induced RNA-binding protein, HuR targets 3'-UTR region of IL-6 mRNA and enhances its stabilization in periodontitis

Abstract

RNA-binding proteins (RBPs) regulate mRNA stability by binding to the 3'-UTR region of mRNA. Human antigen-R (HuR), one of the RBPs, is involved in the progression of diseases, such as rheumatoid arthritis, diabetes mellitus, some inflammatory diseases. Interleukin (IL)-6 is a major inflammatory cytokine regulated by HuR binding to mRNA. Periodontal disease (PD) is also an inflammatory disease caused by elevations in IL-6 following an infection by periodontopathognic bacteria. The involvement of HuR in the progression of PD was assessed using in vitro and in vivo experiment.

Immunohistochemistry of inflamed periodontal tissue showed the strong staining of HuR in the epithelium and connective tissue. HuR mRNA and protein level was increased following a stimulation with Porphyromonas gingivalis (Pg), one of the periodontopathogenic bacteria, LPS derived from Pg (PgLPS), and tumor necrosis factor (TNF)-α in OBA-9, an immortalized human gingival epithelial cell. The luciferase activity of 3'-UTR of IL-6 mRNA was increased by TNF-α, Pg, and PgLPS in OBA-9. Luciferase activity was also increased in HuR-overexpressing OBA-9 following a bacterial stimulation. The down-regulation of HuR by siRNA resulted in a decrease in the mRNA expression and production of IL-6. In contrast, the overexpression of HuR increased IL-6 mRNA expression and production in OBA-9. The HuR inhibitor, quercetin suppressed Pg-induced HuR mRNA expression and IL-6 production in OBA-9. An oral inoculation with quercetin also inhibited bone resorption in ligature-induced periodontitis model mice as a result of downregulation of IL-6. These results show that HuR modulates inflammatory responses by regulating IL-6. This article is protected by copyright. All rights reserved.

Surreptitious apple cider vinegar treatment of a melanocytic nevus: Newly described histologic features

Analysis of the number of enlarged pores according to site, age, and sex

Abstract

Background

Increasing the number of enlarged pores causes cosmetic problems. The difference in the number of enlarged pores according to facial site, age, and sex is unclear.

Objective

To analyze the distribution of the number of enlarged pores according to facial site, age, and sex.

Methods and materials

We analyzed the number of the enlarged pores and the percentage of wrinkles in the nose, forehead, and cheek from 434 polarized images. The measurement results were analyzed according to site, age, and sex. Relationship between enlarged pore counts and wrinkle severity was also analyzed. The study was conducted by using DermaVision,™ which can take cross-polarization, parallel polarization, and ultraviolet light images.

Results

The enlarged pores of the nose and forehead were more prominent than in the cheeks. Pore counts were increased with age, and the increment was significant between the 30's and 40's. There was no significant difference by gender. Enlarged pore counts were related to wrinkle severity.

Conclusions

The number of enlarged pores differs depending on body site and increased with age. The enlarged pore counts correlate with wrinkle severity and the correlation varies depending on the body site.

Allergic contact dermatitis caused by triethylenetetramine: the glue is the clue

Different concentrations and volumes of p-phenylenediamine in pet. (equivalent doses) are associated with similar patch test outcomes: a pilot study

SUMMARY

Background

Concern about causing active sensitization when patch testing is performed with p-phenylenediamine (PPD) 1% pet. has led to a recommendation to use PPD 0.3% pet. as a potentially safer preparation. However, the dose per area of allergen delivered, and hence the risk of active sensitization, depend on the amount dispensed into the patch test chamber, which can vary widely.

Objective

To evaluate whether patch testing with equivalent doses of different concentrations of PPD in pet. is associated with similar outcomes.

Methods

Seventeen known PPD-sensitive subjects were patch tested with different volumes and concentrations of PPD in pet. that deliver the same allergen dose per unit area (6 mg of PPD 1% pet. and 20 mg of PPD 0.3% pet. in Finn Chambers®, both equivalent to ∼ 0.09 mg/cm²).

Results

Eleven patients (65%) had positive reactions to both doses; 4 patients (24%) had negative results [percentage agreement of 88% (15/17)]. One patient each had a positive reaction to only one dose.

Conclusions

The 88% concordance suggests that dose per unit area is more important in determining reactions to allergens than the excipient volume dispensed. Patch testing with a smaller volume of 1% PPD may be a reasonable alternative to testing with 20 mg of 0.3% PPD.

Ecotoxicity of the nonsteroidal ecdysone mimic RH-5849 to Daphnia magna

Abstract

The nonsteroidal ecdysone mimic 1,2-dibenzoyl-1-tert-butylhydrazine (RH-5849), a novel insect growth regulator, is mainly registered for use in rice fields. So far, its toxicity and ecological risks towards aquatic cladoceran invertebrates remain unclear. In this study, RH-5849 was evaluated for its acute and 21-day chronic toxicity towards Daphnia magna. The viability, morphology, growth, and reproduction of D. magna were observed to establish a concentration-toxicity relationship associated with the RH-5849 exposure. In addition, the relationship between the changes of physiological and biochemical indices and the chronic indices was analyzed in order to find potential early warning indicators in D. magna to the chronic risk of RH-5849 exposure. The results showed that the 48-h EC₅₀ of acute immobilization and EC₅₀ of 21-day survival of RH-5849 on D. magna were 45.3 and 1.34 mg/L, respectively. Chronic exposure to RH-5849 mainly affected the reproductive parameters of D. magna and the no observed effect concentration (NOEC) and the EC₅₀ were 0.050 and 0.5423 mg/L, respectively. The number of offspring per female reduced significantly after 21-day exposure to 0.10 mg/L of RH-5849. The morphological changes, manifested in head width and body length, the length of the helmet or apical spine, and the curvature and transparency of the body, were observed in RH-5849-treated groups. Moreover, it was found that the alkaline phosphatase activity in D. magna after 5–7-day exposure was positively correlated with the number of offspring per female after 21 days. These results indicate the potential risk of RH-5849 towards aquatic crustaceans should be taken into consideration when applied to rice fields.

Arsenic hyperaccumulation in Pityrogramma calomelanos L. (Link): adaptive traits to deal with high metalloid concentrations

Abstract

Pityrogramma calomelanos is interestingly the single non-Pteris arsenic (As)-hyperaccumulating fern. It has been pointed as a potential species for phytoremediation and a model plant to study the As toxicity and its mechanisms of action. In order to investigate the morphoanatomical traits associated to As tolerance, P. calomelanos plants were exposed to different As concentrations in hydroponic solution. At low As dose (1 mM As), 90% of the As accumulated in plants was allocated in shoots, and no symptoms of As stress were observed in fronds and roots. Under higher As exposure (10 and 30 mM As), 81–74% of the total As in plants was present in shoots, and apical and marginal necroses on pinnae were observed. Anatomical observations showed that As induces damages mainly in the secondary veins and adjacent cells. High amounts of phenols were observed in pinna tissues of control and treated plants. In the roots, As promoted slight alterations as detachment of border-like cells and accumulation of granular substances in cortical cells. The high root-to-shoot As translocation and the constitutive presence of phenols and border-like cells protecting the root tips showed to be adaptive traits that allow P. calomelanos to survive in contaminated sites.

Combined Fe/P and Fe/S ratios as a practicable index for estimating the release potential of internal-P in freshwater sediment

Abstract

Release of phosphorus (P) from sediment is a major source of P in many freshwater lakes. Currently, assessing the ability of sediment to release P, which is valuable to the management of water eutrophication, remains a challenge. Thus, the purpose of this study was to find effective indexes for predicting the release potential of internal-P. In this study, high-resolution diffusive gradients in thin films (DGT) and conventional sequential extraction were used to characterize the distribution and speciation of P, iron (Fe), and sulfur (S) in the surface sediment of a mildly eutrophic reservoir in southwestern China. Sediment samples exhibited large variations in Fe, S, and P, thereby providing favorable conditions for investigating the effects of Fe and S on sediment P mobilization. In contrast to traditional knowledge, our results show that total P (TP) and redox-sensitive P(BD-P) are poorly correlated with releasable P(DGT-P). This implies that high levels of sedimentary TP and BD-P do not necessarily result in an elevated release of internal-P under anaerobic conditions. Sedimentary P release was greatly suppressed at ratios of Fe/P > 30 and Fe/S > 6. Significant positive correlations between DGT-P and DGT-Fe or DGT-S suggest that Fe and S play an important role in governing the mobility of sedimentary P. These results support the combined Fe/P and Fe/S ratios as an effective and practicable index for assessing the ability of sediment to release P. Thus, our study provides a new and simple method for assessing sedimentary P pollution in freshwater ecosystems.

Distribution and mobility of exogenous copper as influenced by aging and components interactions in three Chinese soils

Abstract

Copper contamination of soils is a global environmental problem. Soil components (organic matter, clay minerals, and microorganisms) and retention time can govern the adsorption, fixation, and distribution of copper. This study evaluated the interaction effects of soil components and aging on the distribution of exogenous copper. Three typical Chinese soils (Ultisol, Alfisol, and Histosol) were collected from Hunan, Henan, and Heilongjiang Provinces. Soils were incubated with rice straw (RS) and engineered bacteria (Pseudomonas putida X4/pIME) in the presence of exogenous copper for 12 months. Sequential extraction was employed to obtain the distribution of Cu species in soils, and the mobility factors of Cu were calculated. The relationships between soil properties and Cu fractions were analyzed with stepwise multiple linear regression. The results show that organic carbon plays a more important role in shaping the distribution of relatively mobile Cu, and iron oxides can be more critical in stabilizing Cu species in soils. Our results suggest that organic matter is the most important factor influencing copper partitioning in Ultisols, while iron oxides are more significant in Alfisols. The mobility of exogenous Cu in soils depends largely on organic carbon, amorphous Fe, and aging. The introduction of both rice straw and rice straw + engineered bacteria enhanced the stabilization of Cu in all the three soils during aging process. The introduction of bacteria could reduce copper mobility, which was indicated by the lowest mobility factors of Cu for the treatment with bacteria in Black, Red, and Cinnamon soils at the first 4, 8, and 8 months, respectively. Different measures should be taken into account regarding the content of organic matter and iron oxides depending on soil types for the risk assessment and remediation of Cu-contaminated soils.

Effects of lanthanum and silicon stress on bio-sequestration of lanthanum in phytoliths in rice seedlings

Abstract

Plant phytoliths are important for silicon (Si) cycling in natural ecosystems; however, their role in lanthanum (La) sequestration in plants is still unclear. In the present study, we elucidated the mechanism of La-induced damage to the growth of rice (Oryza sativa L.) seedling from the viewpoint of the La sequestration by phytoliths (PhytLa). The phytoliths were extracted by using the microwave digestion method. La concentrations within the plants and phytoliths were determined by a modified lithium metaborate fusion method. Analysis showed that pretreatment with low La concentration not only promoted photosynthesis and transpiration in rice but also enhanced the sequestration ability of phytoliths on La. Conversely, high La concentration inhibited photosynthesis and transpiration in rice and the ability of phytoliths to sequester La. Moreover, high Si concentrations promoted the sequestration ability of phytoliths during these processes. Promotion of combined stress of La and Si on the ability of rice seedling was stronger than that of the single La stress. The sequestration ability of phytoliths in different parts of rice varied significantly, following the order: stem > leaf > root. This pattern could be attributed to factors such as the production of various phytolith morphotypes (such as tubes) and PhytLa, PhytLa efficiency, La accumulation, and the rate of photosynthesis and transpiration in different parts of rice seedlings. This study demonstrated that La uptake in rice seedlings was affected by the presence of Si in the medium, and phytolith played a crucial role in the bio-sequestration of La and assuaged the damage caused by La in rice seedlings.

Graphical abstract

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Poor medical care for people with migraine in Europe – evidence from the Eurolight study

Migraine is prevalent everywhere, and disabling. It is also neglected: consequently, it is under-diagnosed and undertreated. We analysed data from the Eurolight study on consultations and utilization of migrai...

Annular erythema nodosum leprosum reaction in a young male: a rare presentation