bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of bisphosphonate as an adjunct to nonsurgical periodontal therapy in the management of periodontal disease: a systematic review
Authors: Akram Zohaib , Abduljabbar Tariq , Kellesarian Sergio Varela , Abu Hassan Mohamed Ibrahim , Javed Fawad , Vohra Fahim
Published: October 2016

Aims

The aim of this systematic review was to assess the efficacy of bisphosphonate therapy as an adjunct to scaling and root planing (SRP) in the management of periodontitis.

Methods

Databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Cochrane Oral Health Group Trials Register databases) were searched up to and including July 2016. The primary outcome was probing depth (PD), and the secondary outcomes were changes in clinical attachment level (CAL) and bone defect (BD) fill. The mean differences (MD) of outcomes and 95% confidence intervals (CI) for each variable were calculated using random effect model.

Results

Eight clinical studies were included. Seven studies used alendronate as an adjunct to SRP; of these, four studies used topical application and three used oral alendronate. Considering the effects of adjunctive bisphosphonates as compared to SRP alone, a high degree of heterogeneity for PD (Q value = 39.6, P < 0.0001, I2 = 87.38%), CAL (Q value = 13.65, P = 0.008, I2 = 70.71%), and BD fill (Q value = 53.26, P < 0.0001, I2 = 92.49%) was noticed among both the groups. Meta‐analysis showed a statistically significant PD reduction (MD = –1.18, 95% CI = –1.91 to –0.44, P = 0.002), CAL gain (MD = –0.69, 95% CI = –1.20 to –0.18, P = 0.008) and BD fill (MD = –2.36, 95% CI = –3.64 to –1.08, P < 0.001) for SRP + bisphosphonate treatment vs. SRP alone.

Conclusions

Adjunctive bisphosphonate therapy appears to be effective in managing periodontitis, however, due to the potential risk of osteonecrosis of the jaws and short‐term follow‐up of the studies, their clinical application is debatable.
Biomarker‐guided clinical development of the first‐in‐class anti‐inflammatory FPR2/ALX agonist ACT‐389949
Authors: Stalder Anna K. , Lott Dominik , Strasser Daniel S. , Cruz Hans G. , Krause Andreas , Groenen Peter M.A. , Dingemanse Jasper
Published: October 2016

Aims

The main objectives of these two phase I studies were to investigate safety and tolerability as well as the pharmacokinetic/pharmacodynamic profile of the novel potent and selective formyl peptide receptor type 2 (FPR2)/Lipoxin A4 receptor (ALX) agonist ACT‐389949. A challenge model was used to assess the drug's anti‐inflammatory potential, with the aim of selecting a dosing regimen for future patient studies.

Methods

Two double‐blind, randomized phase I studies investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of ACT‐389949 at different doses and dosing regimens. Drug exposure was correlated with target engagement markers such as receptor internalization and cytokine measurements. The effect of FPR2/ALX agonism on neutrophil migration was studied in a lipopolysaccharide (LPS) inhalation model.

Results

ACT‐389949 was well tolerated. Maximum concentrations were reached around 2 h after dosing, with a mean terminal half‐life of 29.3 h [95% confidence interval (CI) 25.5, 33.7]. After multiple‐dose administration, exposure increased by 111% (95% CI 89, 136), indicating drug accumulation.

Administration of ACT‐389949 resulted in a dose‐dependent, long‐lasting internalization of FPR2/ALX into leukocytes. Pro‐ and anti‐inflammatory cytokines were dose‐dependently but transiently upregulated only after the first dose. No pharmacological effect on neutrophil count was observed in the LPS challenge test performed at steady state.

Conclusions

FPR2/ALX agonism with ACT‐389949 was shown to be safe and well tolerated in healthy subjects. Receptor internalization and downstream mediators pointed towards a desensitization of the system, which may explain the lack of effect on neutrophil recruitment in the LPS challenge model.
Distinct Metabolic Profile of Inhaled Budesonide and Salbutamol in Asthmatic Children during Acute Exacerbation
Authors: Quan‐Jun Yang , Jian‐Ping Zhang , Jian‐Hua Zhang , Yong‐Long Han , Bo Xin , Jing‐Xian Zhang , Bona Dai , Yuan Zhang , Cheng Guo
Published: October 2016

Inhaled budesonide and salbutamol represent the most important and frequently used drugs in asthmatic children during acute exacerbation. However, there is still no consensus about their resulting metabolic derangements; thus, this study was conducted to determine the distinct metabolic profiles of these two drugs. A total of 69 children with asthma during acute exacerbation were included, and their serum and urine were investigated using high‐resolution nuclear magnetic resonance (NMR). A metabolomics analysis was performed using a principal component analysis and orthogonal signal correction–partial least squares using SIMCA‐P. The different metabolites were identified, and the distinct metabolic profiles were analysed using MetPA. A high‐resolution NMR‐based serum and urine metabolomics approach was established to study the overall metabolic changes after inhaled budesonide and salbutamol in asthmatic children during acute exacerbation. The perturbed metabolites included 22 different metabolites in the serum and 21 metabolites in the urine. Based on an integrated analysis, the changed metabolites included the following: increased 4‐hydroxybutyrate, lactate, cis‐aconitate, 5‐hydroxyindoleacetate, taurine, trans‐4‐hydroxy‐l‐proline, tiglylglycine, 3‐hydroxybutyrate, 3‐methylhistidine, glucose, cis‐aconitate, 2‐deoxyinosine and 2‐aminoadipate; and decreased alanine, glycerol, arginine, glycylproline, 2‐hydroxy‐3‐methylvalerate, creatine, citrulline, glutamate, asparagine, 2‐hydroxyvalerate, citrate, homoserine, histamine, sn‐glycero‐3‐phosphocholine, sarcosine, ornithine, creatinine, glycine, isoleucine and trimethylamine N‐oxide. The MetPA analysis revealed seven involved metabolic pathways: arginine and proline metabolism; taurine and hypotaurine metabolism; glycine, serine and threonine metabolism; glyoxylate and dicarboxylate metabolism; methane metabolism; citrate cycle; and pyruvate metabolism. The perturbed metabolic profiles suggest potential metabolic reprogramming associated with a combination treatment of inhaled budesonide and salbutamol in asthmatic children.
Lipid‐soluble Cigarette Smoke Particles Induced Vascular Endothelin Type A Receptor Up‐Regulation through Activation of ERK1/2 Signal Pathways
Authors: Zhang Yaping , Zhang Wei , Edvinsson Lars , Xu Cang‐Bao
Published: October 2016

Abnormal contraction of vessels termed ‘vasospasm’ is associated with various cardiovascular diseases. Smoking is a well‐known risk factor that increases vasospasm. However, the molecular mechanisms by which smoking leads to vasospasm and cardiovascular disease are not fully understood. This study was designed to examine whether DMSO‐extracted cigarette smoke particles (DSP) could induce up‐regulation of vascular endothelin type A (ETA) receptors, and whether ETA receptor is up‐regulated through activation of extracellular regulated protein kinases 1 and 2 (ERK1/2) signal pathways. Mesenteric arterial segments from rats were cultured in the presence of DSP, water‐extracted cigarette smoke particles (WSP) or equivalent concentration of nicotine for up to 24 hr. The results showed that DSP, but not WSP or nicotine, induced ETA receptor up‐regulation with increased ETA receptor‐mediated contraction (myograph, p < 0.001). Simultaneously, the expression of ETA receptor mRNA (real‐time PCR, p < 0.001) and protein (immunohistochemistry) were enhanced in the smooth muscle cells, suggesting that the lipid‐soluble substances contained in cigarette smoke were responsible for the effects of DSP. Actinomycin D (a general transcriptional inhibitor) decreased ETA receptor mRNA expression and attenuated receptor‐mediated contraction (p < 0.001), while DSP accelerated ETA receptor mRNA degradation (p < 0.01) and promoted the translation of ETA receptor mRNA into protein. Furthermore, the up‐regulation of ETA receptors was significantly attenuated by inhibition of ERK1/2 signal pathways (p < 0.001). In conclusion, DSP most likely activate ERK1/2 signal pathway‐mediated transcriptional and post‐transcriptional (translational) mechanisms that lead to vascular ETA receptor up‐regulation, which might contribute to vasospasm and the development of smoking‐associated cardiovascular diseases.
MicroRNA 200a inhibits erythroid differentiation by targeting PDCD4 and THRB
Authors: Li Yanming , Zhang Qian , Du Zhenglin , Lu ZhiChao , Liu Shuge , Zhang Lu , Ding Nan , Bao Binghao , Yang Yadong , Xiong Qian , Wang Hai , Zhang Zhaojun , Qu Hongzhu , Jia Haibo , Fang Xiangdong
Published: October 2016

Previous studies on erythropoiesis revealed that microRNAs (miRNAs) play a critical role in erythroid differentiation. Given the abundance of identified miRNAs and the limited understanding of erythroid miRNAs, additional examination is required. Here, two sets of erythroid differentiation miRNome data were analysed to screen for novel erythroid‐inhibiting miRNAs. MIR200A was selected based on its pattern of downregulated expression in the miRNome datasets during induction of erythroid differentiation. Overexpression of MIR200A in K562 and TF‐1 cells confirmed its inhibitory role in erythroid differentiation. Further in vivo study indicated that overexpression of mir200a inhibited primitive erythropoiesis of zebrafish. Transcriptome analyses after MIR200A overexpression in TF‐1 cells indicated a significant role in regulating erythroid function and revealed potential regulation networks. Additionally, bioinformatics and experimental analyses confirmed that PDCD4 (programmed cell death 4) and THRB (thyroid hormone receptor, beta) are both targets of MIR200A‐3p. Gain‐ and loss‐of‐function studies of PDCD4 and THRB revealed that the two targets were capable of promoting erythroid gene expression. Overall, our results revealed that microRNA 200a inhibits erythroid differentiation by targeting PDCD4 and THRB.
Assessing moderated mediation in linear models requires fewer confounding assumptions than assessing mediation
Authors: Loeys Tom , Talloen Wouter , Goubert Liesbet , Moerkerke Beatrijs , Vansteelandt Stijn
Published: October 2016

It is well known from the mediation analysis literature that the identification of direct and indirect effects relies on strong no unmeasured confounding assumptions of no unmeasured confounding. Even in randomized studies the mediator may still be correlated with unobserved prognostic variables that affect the outcome, in which case the mediator's role in the causal process may not be inferred without bias. In the behavioural and social science literature very little attention has been given so far to the causal assumptions required for moderated mediation analysis. In this paper we focus on the index for moderated mediation, which measures by how much the mediated effect is larger or smaller for varying levels of the moderator. We show that in linear models this index can be estimated without bias in the presence of unmeasured common causes of the moderator, mediator and outcome under certain conditions. Importantly, one can thus use the test for moderated mediation to support evidence for mediation under less stringent confounding conditions. We illustrate our findings with data from a randomized experiment assessing the impact of being primed with social deception upon observer responses to others’ pain, and from an observational study of individuals who ended a romantic relationship assessing the effect of attachment anxiety during the relationship on mental distress 2 years after the break‐up.
The integrative role of cryo electron microscopy in molecular and cellular structural biology
Authors: Orlov Igor , Myasnikov Alexander G. , Andronov Leonid , Natchiar S. Kundhavai , Khatter Heena , Beinsteiner Brice , Ménétret Jean‐François , Hazemann Isabelle , Mohideen Kareem , Tazibt Karima , Tabaroni Rachel , Kratzat Hanna , Djabeur Nadia , Bruxelles Tatiana , Raivoniaina Finaritra , Pompeo Lorenza di , Torchy Morgan , Billas Isabelle , Urzhumtsev Alexandre , Klaholz Bruno P.
Published: October 2016

After gradually moving away from preparation methods prone to artefacts such as plastic embedding and negative staining for cell sections and single particles, the field of cryo electron microscopy (cryo‐EM) is now heading off at unprecedented speed towards high‐resolution analysis of biological objects of various sizes. This ‘revolution in resolution’ is happening largely thanks to new developments of new‐generation cameras used for recording the images in the cryo electron microscope which have much increased sensitivity being based on complementary metal oxide semiconductor devices. Combined with advanced image processing and 3D reconstruction, the cryo‐EM analysis of nucleoprotein complexes can provide unprecedented insights at molecular and atomic levels and address regulatory mechanisms in the cell. These advances reinforce the integrative role of cryo‐EM in synergy with other methods such as X‐ray crystallography, fluorescence imaging or focussed‐ion beam milling as exemplified here by some recent studies from our laboratory on ribosomes, viruses, chromatin and nuclear receptors. Such multi‐scale and multi‐resolution approaches allow integrating molecular and cellular levels when applied to purified or in situ macromolecular complexes, thus illustrating the trend of the field towards cellular structural biology.
Trastuzumab cardiotoxicity: from clinical trials to experimental studies
Authors: Nemeth Balazs T , Varga Zoltan V , Wu Wen Jin , Pacher Pal
Published: October 2016

Epidermal growth factor receptor‐2 (HER‐2) is overexpressed in 20 to 25% of human breast cancers, which is associated with aggressive tumour growth and poor prognosis. Trastuzumab (Herceptin®) is a humanized monoclonal antibody directed against HER‐2, the first highly selective form of therapy targeting HER‐2 overexpressing tumours. Although initial trials indicated high efficacy and a favourable safety profile of the drug, the first large, randomized trial prompted a retrospective analysis of cardiac dysfunction in earlier trials utilizing trastuzumab. There has been ongoing debate on the cardiac safety of trastuzumab ever since, initiating numerous clinical and preclinical investigations to better understand the background of trastuzumab cardiotoxicity and evaluate its effects on patient morbidity. Here, we have given a comprehensive overview of our current knowledge on the cardiotoxicity of trastuzumab, primarily focusing on data from clinical trials and highlighting the main molecular mechanisms proposed.

Linked Articles

This article is part of a themed section on New Insights into Cardiotoxicity Caused by Chemotherapeutic Agents. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.21/issuetoc
Macroecology of parental care in arthropods: higher mortality risk leads to higher benefits of offspring protection in tropical climates
Authors: Santos Eduardo S. A. , Bueno Pedro P. , Gilbert James D. J. , Machado Glauco
Published: October 2016

The intensity of biotic interactions varies around the world, in such a way that mortality risk imposed by natural enemies is usually higher in the tropics. A major role of offspring attendance is protection against natural enemies, so the benefits of this behaviour should be higher in tropical regions. We tested this macroecological prediction with a meta‐regression of field experiments in which the mortality of guarded and unguarded broods was compared in arthropods. Mortality of unguarded broods was higher, and parental care was more beneficial, in warmer, less seasonal environments. Moreover, in these same environments, additional lines of defence further reduced offspring mortality, implying that offspring attendance alone is not enough to deter natural enemies in tropical regions. These results help to explain the high frequency of parental care among tropical species and how biotic interactions influence the occurrence of parental care over large geographic scales. Finally, our findings reveal that additional lines of defences – an oftentimes neglected component of parental care – have an important effect on the covariation between the benefits of parental care and the climate‐mediated mortality risk imposed by natural enemies.
Bevacizumab for non‐small‐cell lung cancer: A nested case control study of risk factors for hemoptysis
Authors: Goto Koichi , Endo Masahiro , Kusumoto Masahiko , Yamamoto Nobuyuki , Ohe Yuichiro , Shimizu Ayaka , Fukuoka Masahiro
Published: October 2016

Potentially life‐threatening, serious hemoptysis is an adverse event associated with bevacizumab in non‐squamous non‐small‐cell lung cancer (NSCLC) trials. Suggested risk factors include central tumor location and cavitation; however, the profile of hemoptysis occurrence in clinical practice is still unclear. A nested case‐control study was conducted to assess the onset profile and risk factors for hemoptysis in bevacizumab‐treated patients in a real‐world setting in Japan. After bevacizumab was approved for NSCLC, physicians registered all NSCLC patients scheduled for bevacizumab therapy, from November 2009 to August 2011. Patients developing grade 2 hemoptysis requiring an injectable hemostatic agent or grade ≥3 hemoptysis were selected as case subjects, matched with four control subjects each. Case report forms were collected after an observation period of 24 weeks. Radiologists assessed blinded thoracic images. Risk factors for hemoptysis were assessed by univariate and stepwise multivariate analysis. Of 6774 patients registered, 23 (0.3%) experienced grade ≥2 drug‐related hemoptysis. A total of 104 patients (21 cases, 83 controls) were analyzed by central reviewers for risk factors of hemoptysis occurrence. In the univariate analysis seven factors were associated with hemoptysis. In the step‐wise multivariate analysis, prior thoracic radiotherapy (P = 0.1844), presence of tumor exposure in the central airway (P = 0.0256) and concomitant radiotherapy (P = 0.1169) were identified as risk factors for hemoptysis. While the incidence of hemoptysis was low in the real‐world setting in Japan, the three risk factors identified, prior thoracic radiotherapy, presence of tumor exposure in the central airway and concomitant radiotherapy, should be considered when selecting patients for bevacizumab treatment. Although technically classed as a clinical trial, a nested case‐control study was a non‐interventional surveillance study analyzing all NSCLC patients receiving bevacizumab in Japan, therefore it was not registered as a phase II/III clinical trial would be.
Comparison of tumor‐infiltrating lymphocytes between primary and metastatic tumors in breast cancer patients
Authors: Ogiya Rin , Niikura Naoki , Kumaki Nobue , Bianchini Giampaolo , Kitano Shigehisa , Iwamoto Takayuki , Hayashi Naoki , Yokoyama Kozue , Oshitanai Risa , Terao Mayako , Morioka Toru , Tsuda Banri , Okamura Takuho , Saito Yuki , Suzuki Yasuhiro , Tokuda Yutaka
Published: October 2016

The presence of tumor‐infiltrating lymphocytes (TILs) is associated with favorable long‐term outcome in breast cancer. However, little is known about changes in TILs during metastatic progression. To confirm our hypothesis that malignant tumors escape from the host immune system during metastasis, we evaluated the percentage of TILs in paired samples of primary and metastatic breast tumors. We retrospectively identified 25 patients with human epidermal growth factor receptor‐2 (HER2+, n = 14) and triple negative (TN, n = 11) early breast cancer diagnosed between 1990 and 2009 at Tokai University Hospital (Isehara, Japan) and who subsequently experienced regional or distant recurrence confirmed by tumor biopsy/resection. Hematoxylin–eosin‐stained slides of these paired samples were evaluated for stromal TILs. Immunohistochemical staining was carried out using primary antibodies against CD4, CD8, Foxp3, programmed cell death ligand 1 (PD‐L1), PD‐L2, and HLA class I for characterizing the TILs and breast tumors. The percentage of TILs in the primary tumors was significantly higher (average 34.6%) than that in metastatic tumors (average 15.7%) (paired t‐test, P = 0.004) and that of CD8+ and CD4+ T cells significantly decreased from primary to metastatic tumors (paired t‐test, P = 0.008 and P = 0.026, respectively). The PD‐L1, PD‐L2, and HLA class I antibody expression changed from positive to negative and vice versa from the primary to the metastatic tumors. Tumors at first metastatic recurrence in HER2+ and TN breast cancers have a lower percentage of TILs and CD8+ and CD4+ T cells compared to primary tumors, which indicates that immune escape plays a role in tumor progression.
Metacognition in Early Childhood: Fertile Ground to Understand Memory Development?
Authors: Geurten Marie , Willems Sylvie
Published: October 2016

Metacognition is a critical factor that appears to be involved in improving episodic memory during childhood. However, as metacognitive abilities emerge relatively late in development, they have not been expected to influence children's memory performance before age 7. Nevertheless, in recent studies, as early as age 3, children rely on basic metacognitive abilities to evaluate their memory and use the result of this evaluation to regulate their memory performance. In this article, we consider evidence for the early development of metacognitive skills. We then review studies indicating that children can use inference rules based on the results of their introspection (monitoring) to regulate their memory decisions, demonstrating the early use of several metacognitive heuristics. Finally, we discuss preliminary findings indicating that changes in how children use metacognitive heuristics can account for changes in episodic memory throughout childhood.
Survey of glaucoma surgical preferences and post‐operative care in the United Kingdom
Authors: Rodriguez‐Una Ignacio , Azuara‐Blanco Augusto , King Anthony J
Published: October 2016

Background

To evaluate the spectrum of glaucoma surgery and the post‐operative follow‐up regimes undertaken among glaucoma specialists in the United Kingdom.

Design

National survey.

Participants

Seventy‐five glaucoma specialists (consultants and fellows).

Methods

An eight‐question survey was emailed to all glaucoma subspecialists members of the United Kingdom and Eire Glaucoma Society.

Main Outcome Measures

Surgery undertaken, post‐operative management, awareness of intervention tariff and handling of the follow‐up burden generated through surgery.

Results

Almost all the participants (74/75: 99%) routinely performed trabeculectomy, 54 responders (72%) undertook tube surgery and Minimally Invasive Glaucoma Surgery (MIGS) was more frequently undertaken (33.0%) than non‐penetrating surgery (23%).

In general, for patients with advanced glaucoma requiring a low target intraocular pressure (IOP), the most frequent primary intervention was trabeculectomy (99%), followed by tubes (64%). Similarly, in patients with less advanced glaucoma requiring moderate target IOP, participants preferred trabeculectomy (99%), followed by MIGS (60%). By the first 6 months after the procedure, trabeculectomy and Baerveldt tube implant required a larger number of postoperative visits (9 and 7, respectively), than iStent® and non‐penetrating deep sclerectomy (3 and 5, respectively).

The majority of participants were not aware of the costs of their interventions.

Conclusions

A wide variety of glaucoma surgery techniques are undertaken. Post‐operative follow‐up regimes are variable between techniques and for surgeons using the same technique. Trabeculectomy requires more follow‐up than any other intervention. For patients requiring low IOP, trabeculectomy is the operation of choice for most surgeons.
THE 80% PENSION FUNDING TARGET, HIGH ASSUMED RETURNS, AND GENERATIONAL INEQUITY
Authors: Costrell Robert M.
Published: October 2016

Generational inequity in pension funding is highly sensitive to the lax policies of 80% funding targets and high assumed returns to investment. I develop a simple, powerful relationship between steady‐state (SS) inequity in contributions—the percent of extra contributions to fund prior cohorts—and the SS unfunded ratio. I then show how the SS unfunded ratio is governed by x% funding targets and the gap between assumed and true returns. The SS degree of inequity is over 60% under an 80% funding target and over 50% with a one‐point gap between assumed and true returns. (JEL H75)
Supporting Conservation: The Roles of Flagship Species and Identifiable Victims
Authors: Thomas‐Walters Laura , J Raihani Nichola
Published: October 2016

Psychological insights into human behavior can have enormous applied value for promoting charitable giving. Nevertheless, the application of these insights to conservation appeals featuring nonhuman animals has scarcely been explored. Although people often donate more when presented with single “identifiable” victims, whether this effect also extends to nonhumans is not known. Similarly, although many conservation appeals feature flagship species, it is unclear whether flagship species generate increased donations. We experimentally investigated how (1) identifiable versus statistical beneficiaries and (2) flagship versus nonflagship species affected donations to a conservation charity. Unexpectedly, subjects did not donate more when presented with single identifiable beneficiaries rather than groups of beneficiaries. Flagship species, on the other hand, increased donation amounts relative to appeals featuring nonflagship species. We discuss how these findings can inform and improve the effectiveness of conservation fundraising appeals.
Zinc sulfate improved the unbalanced T cell profiles in Der p‐allergic asthma: An ex vivo study
Authors: Tsai Yu Lin , Ko Wang‐Sheng , Hsiao Jung‐Lung , Pan Hsin‐Hung , Chiou Ya‐Ling
Published: October 2016

Introduction

In the pathogenesis of asthma, an imbalance between helper T (Th) 1/Th2 and Th17/Treg cells is believed to play a key role in asthmatic inflammatory responses. Some studies indicated that zinc deficiency increases inflammatory factor production and worsens asthma. However, the effects of zinc on T cell profiles to reduce inflammatory response remain unclear.

Objectives

We investigated the beneficial effects of zinc on isolated cell populations and cytokine levels from patients with asthma.

Methods

Thirty‐six individuals Dermatophagoides pteronyssinus (Der p)‐allergic and 31 healthy subjects were enrolled in the study, and peripheral blood mononuclear cells (PBMCs) were collected. Harvested PBMCs were stimulated with recombinant Der p antigen in the presence or absence of zinc sulfate (25 μM or 50 μM) for 48 h. Cell surface markers and intracellular cytokine levels were examined by flow cytometry. The pro‐inflammatory factors in plasma and culture supernatants were measured by commercial enzyme‐linked immunosorbent assay.

Results

Zinc sulfate dramatically reduced the proportions of Th2 and Th17 cells, but increased that of Th1 and Treg cells. Zinc sulfate also markedly reduced the levels of interleukin (IL)‐4 and IL‐17, but increased the levels of IFN‐γ.

Conclusions

Zinc ameliorates the imbalance in T cell profiles and could be a potential adjuvant therapy for Der p‐induced allergic hypersensitivity.
The use of robotic surgery in abdominal organ transplantation: A literature review
Authors: Levi Sandri Giovanni B. , de Werra Edoardo , Mascianà Gianluca , Guerra Francesco , Spoletini Gabriele , Lai Quirino
Published: October 2016

Minimally invasive surgical approaches in transplantation are gaining increasing interest, and many centers are reporting their, mainly laparoscopic, experiences. Robotic surgery (RS) has some hypothetical advantages over traditional laparoscopy and has been successfully applied, although infrequently to organ transplantation. Our goal was to review and critique the publications reporting RS use in organ transplantation. Most of the RS experience has been with living renal donor organ procurement and, to a lesser extent, with RS procedures in the transplant recipient. The available literature suggests that RS appears to be a safe surgical alternative to standard open procedures. RS in living liver donor surgery remains limited, and more experience is required before commenting on RS‐related outcomes RS in pancreatic transplantation is exceedingly rare. The enhanced precision and ergonomics of RS may expand its applicability to liver living donation and pancreas transplantation at some point in the future.
Evaluation of MDRD4, CKD‐EPI, BIS‐1, and modified Cockcroft–Gault equations to estimate glomerular filtration rate in the elderly renal‐transplanted recipients
Authors: David‐Neto Elias , Triboni Ana Heloisa Kamada , Ramos Fernanda , Agena Fabiana , Galante Nelson Zocoler , Altona Marcelo , Lemos Francine Brambate Carvalhinho , Sapienza Marcelo Tatit , Nahas William Carlos
Published: October 2016

Equations to estimate glomerular filtration rate (eGFR) were developed in patients using the variables age, body weight, and serum creatinine, which may be different in the elderly. Elderly renal transplant patients (EG; n=70; mean age 65 ± 4 y) who measured plasma 51Cr‐EDTA‐Clearance (mGFR) had mGFR compared to eGFR obtained by the Cockcroft–Gault corrected by body surface area (CG‐BSA), the modification of diet in renal disease (MDRD‐4), the Berlin Initiative Study (BIS‐1), and the chronic kidney disease epidemiology collaboration (CKD‐EPI). Results were validated using a cohort of 43, of the 70 elderly recipients, who performed a second 51Cr‐EDTA‐Clearance. Mean mGFR was 47 ± 16 mL/min/1.73 m2 and statistically lower than eGFR by MDRD (52 ± 19, P=.001) and BIS‐1 (51 ± 13, P=.007) but not different from the CG‐BSA (47 ± 15) and CKD‐EPI (49 ± 18). The CKD‐EPI and CG‐BSA presented the lowest bias but only CKD‐EPI also showed the highest 30% and 10% accuracy. The same findings were repeated in the validation set. For a cohort of elderly recipients ≥65 years (n=35, 68 ± 3y), the CKD‐EPI performed better with the lowest bias (0 ± 12 mL/min/1.73 m2) and best 30% and 10% accuracy. The CKD‐EPI equation is a valuable tool to monitor GFR in the elderly RTx recipients.
Using direct mail to promote organ donor registration: Two campaigns and a meta‐analysis
Authors: Feeley Thomas H. , Quick Brian L. , Lee Seyoung
Published: October 2016

Background

Two direct mail campaigns were undertaken in Rochester and Buffalo, New York, with the goal of enrolling adults aged 50‐64 years into the state organ and tissue donation electronic registry. Meta‐analytic methods were used to summarize the body of research on the effects of direct mail marketing to promote organ donation registration.

Methods

In the first study, 40 000 mailers were sent to targeted adults in Rochester, New York, and varied by brochure‐only, letter‐only, and letter plus brochure mailing conditions. A follow‐up mailer using letter‐only was sent to 20 000 individuals in Buffalo, New York area. In a second study, campaign results were combined with previously published direct mail campaigns in a random‐effects meta‐analysis.

Results

The overall registration rates were 1.6% and 4.6% for the Rochester and Buffalo campaigns, and the letter‐only condition outperformed the brochure‐only and letter plus brochure conditions in the Rochester area campaigns. Meta‐analysis indicated a 3.3% registration rates across 15 campaigns and 329 137 targeted individuals. Registration rates were higher when targeting 18‐year‐olds and when direct mail letters were authored by officials affiliated with state departments.

Conclusion

Use of direct mail to promote organ donor registration is an inexpensive method to increase enrollments in state registries.
Critical considerations in responding to crystal methamphetamine use in Australian Aboriginal communities
Authors: MacLean Sarah , Hengsen Ross , Stephens Raelene
Published: October 2016

Introduction and Aims

This article identifies factors that participants in a study based in an Australian regional centre believed to be critical to understanding and responding to crystal methamphetamine (ice) use among Aboriginal people.

Design and Methods

The study entailed a participatory methodology involving a university and an Aboriginal community controlled organisation. Semi‐structured interviews conducted with ice users (n = 14), family members (n = 6) and workers (n = 6) were analysed thematically.

Results

Interviewees believed that historical trauma, contemporary disadvantage and racism cohere to produce a market for ice and other drugs within Aboriginal communities. Intense shame prevented some ice users and their families from seeking help, while fear about ice use was exacerbated when suppliers of ice threatened violence. Disconnection from family and community further intensified a sense of isolation and despair. By contrast, family reintegration provided ice users in the study with the strongest motivation for change.

Discussion and Conclusions

Although drawing only on a small sample of participants, the study suggests that Aboriginal people's experiences of ice use may have some distinct characteristics, meaning that tailored responses are required. Interventions should address the shame and ameliorate the fear that surround problematic ice use for families and users, provide help to those who feel trapped because of drug debts and relationships with dealers, and support families to maintain contact with ice users where this is manageable. Supports for users to remain connected to family and community are also critical. The effectiveness of family wellbeing interventions as adjuncts to treatment could be evaluated. [MacLean S, Hengsen R, Stephens R Critical considerations in responding to crystal methamphetamine use in Australian Aboriginal communities Drug Alcohol Rev 2017;36:502‐508]
Climate constrains range expansion of an allochronic population of the pine processionary moth
Authors: Godefroid M. , Rocha S. , Santos H. , Paiva M.‐R. , Burban C. , Kerdelhué C. , Branco M. , Rasplus J.‐Y. , Rossi J.‐P.
Published: October 2016

Aim

Allochronic speciation occurs when sympatric populations sharing similar feeding regimes diverge because they mate at different times. Such speciation mode is fascinating because it permits the study of subsequent adaptations and/or geographic range shifts undergone by the populations that face new ecological constraints. Moreover, exploring whether intraspecific differentiation is accompanied by niche divergence is crucial for planning efficient biodiversity management and invasive species control. Here, we address the topic of potential climatic niche divergence between two sympatric populations of the pine processionary moth Thaumetopoea pityocampa (PPM) that diverged under allochrony. The larval development of a PPM population recently discovered in coastal regions of Portugal, referred to as the summer population (SP), occurs in the spring–summer instead of the autumn–winter as for all other populations of this species.

Location

Portugal.

Methods

We carried out intensive field sampling in the area where both populations are sympatric and calibrated spread (MigClim approach) and species distribution models (ensemble forecasting approach) to depict the response of SP to environment and predict its potential range under current and future climatic conditions.

Results

Since its discovery in 1997, the distribution of SP has been expanding along the Western coasts of Portugal. Still, its establishment in inland regions failed, even though suitable hosts occur. Our models identify maximal temperatures as the main constraint explaining SP absence from inland regions. The coastal area where winter populations and SP co‐occur displays unique climatic conditions (moderate maximal and minimal temperatures), which enable the coexistence of these populations with totally different phenologies. The models predict a future decrease of SP range due to climate warming.

Main conclusions

We show here that a climatic niche shift occurred following allochronic divergence. This study highlights how climate differentially affects allochronic populations and how considering intraspecific diversity is crucial when predicting species responses to climate change.
Auditory toxicity in late preterm and term neonates with severe jaundice
Authors: Amin Sanjiv B , Saluja Satish , Saili Arvind , Laroia Nirupama , Orlando Mark , Wang Hongyue , Agarwal Asha
Published: October 2016

Aim

Jaundice may cause auditory toxicity (auditory neuropathy and hearing loss). However, total serum bilirubin (TSB) does not discriminate neonates at risk for auditory toxicity. We compared TSB, bilirubin:albumin molar ratio (BAMR), and unbound bilirubin for their association with auditory toxicity in neonates with severe jaundice (TSB ≥342μmol/L, or that met exchange transfusion).

Method

Neonates greater or equal to 34 weeks gestational age with severe jaundice during the first 2 postnatal weeks were eligible for prospective cohort study, unless they had craniofacial malformations, chromosomal disorders, toxoplasmosis, other infections, rubella, cytomegalovirus, herpes simplex infections, surgery, or family history of congenital deafness.

Results

Twenty‐eight out of 100 neonates (mean gestational age 37.4wks; 59 males, 41 females) had auditory toxicity. Peak unbound bilirubin, but not peak TSB and BAMR, was associated with auditory toxicity (p<0.05) in neonates with severe (TSB <427.5μmol/L) and extreme hyperbilirubinemia (TSB ≥427.5μmol/L). Area under the receiver operating characteristic curve for unbound bilirubin (0.78) was significantly greater (p=0.03) than TSB (0.54) among neonates with severe but not extreme hyperbilirubinemia.

Interpretation

Unbound bilirubin is more strongly associated with auditory toxicity than TSB and/or BAMR in greater or equal to 34 weeks gestational age neonates with severe jaundice. Unbound bilirubin is a better predictor than TSB in neonates with severe hyperbilirubinemia.
Pediatric opsoclonus–myoclonus syndrome: the role of functional brain connectivity studies
Authors: Gallerini Simone , Marsili Luca
Published: October 2016

This commentary is on the original article by Chekroud et al. on pages 98–104 of this issue.
TELEWORK: URBAN FORM, ENERGY CONSUMPTION, AND GREENHOUSE GAS IMPLICATIONS
Authors: Larson William , Zhao Weihua
Published: October 2016

A primary motivation of telework policy is to reduce energy consumption and greenhouse gas emissions. Using a numerical simulation of the standard urban model, we show telework causes sprawl, calling into question the idea that telework decreases energy consumption. Overall effects depend on wage changes due to telework, land‐use regulation such as height limits or greenbelts, and the telework participation rate. While energy consumption increases in some scenarios, emissions may fall due to changes in the energy mix between gasoline and other sources. (JEL R11, R28, C60)
SOFT SKILLS, HARD SKILLS, AND THE BLACK/WHITE WAGE GAP
Authors: Fan C. Simon , Wei Xiangdong , Zhang Junsen
Published: October 2016

This study examines the relative importance of soft skills versus hard skills across occupations and its impact on the observed wage gap between Blacks and Whites in the United States. It posits that the Black/White pay gap may vary across occupations that require the use of different types of skills. We classify occupations into hard‐skill intensive versus soft‐skill intensive jobs using the skill content measures of different occupations from the Occupational Information Network (O*Net). We then use data from the National Longitudinal Survey of Youth (NLSY) and Current Population Survey (CPS) to investigate the impact of job skill type on the wage gap. Consistent with our theoretical predictions, we show that this wage gap in white‐collar jobs is smaller for hard‐skills jobs than it is for soft‐skills jobs. Moreover, we demonstrate that, in response to variations in the wage gap across different occupations, Blacks are more likely to self‐select themselves into hard‐skills jobs, ceteris paribus. This shows not only that discrimination against Blacks varies across occupations, but also that such discrimination induces the self‐selection of Blacks into certain occupations. Moreover, this finding highlights the role played by co‐worker/customer discrimination in explaining the racial wage gap in the U.S. labor market. (JEL J15, J31)
Migratory delay leads to reduced passage success of Atlantic salmon smolts at a hydroelectric dam
Authors: Nyqvist Daniel , Greenberg Larry A. , Goerig Elsa , Calles Olle , Bergman Eva , Ardren William R. , Castro‐Santos Theodore
Published: October 2016

Passage of fish through hydropower dams is associated with mortality, delay, increased energy expenditure and migratory failure for migrating fish and the need for remedial measures for both upstream and downstream migration is widely recognised. A functional fish passage must ensure safe and timely passage routes that a substantial portion of migrating fish will use. Passage solutions must address not only the number or percentage of fish that successfully pass a barrier, but also the time it takes to pass. Here, we used radiotelemetry to study the functionality of a fish bypass for downstream‐migrating wild‐caught and hatchery‐released Atlantic salmon smolts. We used time‐to‐event analysis to model the influence of fish characteristics and environmental variables on the rates of a series of events associated with dam passage. Among the modelled events were approach rate to the bypass entry zone, retention rates in both the forebay and the entry zone and passage rates. Despite repeated attempts, only 65% of the tagged fish present in the forebay passed the dam. Fish passed via the bypass (33%), via spill (18%) and via turbines (15%). Discharge was positively related to approach, passage and retention rates. We did not detect any differences between wild and hatchery fish. Even though individual fish visited the forebay and the entry zone on multiple occasions, most fish passed during the first exposures to these zones. This study underscores the importance of timeliness to passage success and the usefulness of time‐to‐event analysis for understanding factors governing passage performance.
Climate‐induced seasonal changes in smallmouth bass growth rate potential at the southern range extent
Authors: Middaugh Christopher R. , Kessinger Brin , Magoulick Daniel D.
Published: October 2016

Temperature increases due to climate change over the coming century will likely affect smallmouth bass (Micropterus dolomieu) growth in lotic systems at the southern extent of their native range. However, the thermal response of a stream to warming climate conditions could be affected by the flow regime of each stream, mitigating the effects on smallmouth bass populations. We developed bioenergetics models to compare change in smallmouth bass growth rate potential (GRP) from present to future projected monthly stream temperatures across two flow regimes: runoff and groundwater‐dominated. Seasonal differences in GRP between stream types were then compared. The models were developed for fourteen streams within the Ozark–Ouachita Interior Highlands in Arkansas, Oklahoma and Missouri, USA, which contain smallmouth bass. In our simulations, smallmouth bass mean GRP during summer months decreased by 0.005 g g−1 day−1 in runoff streams and 0.002 g g−1 day−1 in groundwater streams by the end of century. Mean GRP during winter, fall and early spring increased under future climate conditions within both stream types (e.g., 0.00019 g g−1 day−1 in runoff and 0.0014 g g−1 day−1 in groundwater streams in spring months). We found significant differences in change in GRP between runoff and groundwater streams in three seasons in end‐of‐century simulations (spring, summer and fall). Potential differences in stream temperature across flow regimes could be an important habitat component to consider when investigating effects of climate change as fishes from various flow regimes that are relatively close geographically could be affected differently by warming climate conditions.
High‐order motor cortex in rats receives somatosensory inputs from the primary motor cortex via cortico‐cortical pathways
Authors: Kunori Nobuo , Takashima Ichiro
Published: October 2016

The motor cortex of rats contains two forelimb motor areas; the caudal forelimb area (CFA) and the rostral forelimb area (RFA). Although the RFA is thought to correspond to the premotor and/or supplementary motor cortices of primates, which are higher‐order motor areas that receive somatosensory inputs, it is unknown whether the RFA of rats receives somatosensory inputs in the same manner. To investigate this issue, voltage‐sensitive dye (VSD) imaging was used to assess the motor cortex in rats following a brief electrical stimulation of the forelimb. This procedure was followed by intracortical microstimulation (ICMS) mapping to identify the motor representations in the imaged cortex. The combined use of VSD imaging and ICMS revealed that both the CFA and RFA received excitatory synaptic inputs after forelimb stimulation. Further evaluation of the sensory input pathway to the RFA revealed that the forelimb‐evoked RFA response was abolished either by the pharmacological inactivation of the CFA or a cortical transection between the CFA and RFA. These results suggest that forelimb‐related sensory inputs would be transmitted to the RFA from the CFA via the cortico‐cortical pathway. Thus, the present findings imply that sensory information processed in the RFA may be used for the generation of coordinated forelimb movements, which would be similar to the function of the higher‐order motor cortex in primates.
A resting‐state fMRI study of obese females between pre‐ and postprandial states before and after bariatric surgery
Authors: Wiemerslage Lyle , Zhou Wei , Olivo Gaia , Stark Julia , Hogenkamp Pleunie S. , Larsson Elna‐Marie , Sundbom Magnus , Schiöth Helgi B.
Published: October 2016

Past studies utilizing resting‐state functional MRI (rsfMRI), have shown that obese humans exhibit altered activity in brain areas related to reward compared to normal‐weight controls. However, to what extent bariatric surgery‐induced weight loss alters resting‐state brain activity in obese humans is less well‐studied. Thus, we measured the fractional amplitude of low‐frequency fluctuations from eyes‐closed, rsfMRI in obese females (n = 11, mean age = 42 years, mean BMI = 41 kg/m2) in both a pre‐ and postprandial state at two time points: four weeks before, and four weeks after bariatric surgery. Several brain areas showed altered resting‐state activity following bariatric surgery, including the putamen, insula, cingulate, thalamus and frontal regions. Activity augmented by surgery was also dependent on prandial state. For example, in the fasted state, activity in the middle frontal and pre‐ and postcentral gyri was found to be decreased after surgery. In the sated state, activity within the insula was increased before, but not after surgery. Collectively, our results suggest that resting‐state neural functions are rapidly affected following bariatric surgery and the associated weight loss and change in diet.