bluuebunny/crossref_metadata_2025 huggingface dataset:
Sarcoidosis extent relates to molecular variability
Authors: Monast C S , Li K , Judson M A , Baughman R P , Wadman E , Watt R , Silkoff P E , Barnathan E S , Brodmerkel C
Published: February 2017

The molecular basis of sarcoidosis phenotype heterogeneity and its relationship to effective treatment of sarcoidosis have not been elucidated. Peripheral samples from sarcoidosis subjects who participated in a Phase II study of golimumab [anti-tumour necrosis factor (TNF)-α] and ustekinumab [anti-interleukin (IL)−12p40] were used to measure the whole blood transcriptome and levels of serum proteins. Differential gene and protein expression analyses were used to explore the molecular differences between sarcoidosis phenotypes as defined by extent of organ involvement. The same data were also used in conjunction with an enrichment algorithm to identify gene expression changes associated with treatment with study drugs compared to placebo. Our analyses revealed marked heterogeneity among the three sarcoidosis phenotypes included in the study cohort, including striking differences in enrichment of the interferon pathway. Conversely, enrichments of multiple pathways, including T cell receptor signalling, were similar among phenotypes. We also identify differences between treatment with golimumab and ustekinumab that may explain the differences in trends for clinical efficacy observed in the trial. We find that molecular heterogeneity is associated with sarcoidosis in a manner that may be related to the extent of organ involvement. These findings may help to explain the difficulty in identifying clinically efficacious sarcoidosis treatments and suggest hypotheses for improved therapeutic strategies.
Effect of matrix stiffness on osteoblast functionalization
Authors: Zhang Tao , Lin Shiyu , Shao Xiaoru , Zhang Qi , Xue Changyue , Zhang Shu , Lin Yunfeng , Zhu Bofeng , Cai Xiaoxiao
Published: February 2017

Objectives

Stiffness of bone tissue differs response to its physiological or pathological status, such as osteoporosis or osteosclerosis. Consequently, the function of cells residing in bone tissue including osteoblasts (OBs), osteoclasts and osteocytes will be affected. However, to the best of our knowledge, the detailed mechanism of how extracellular matrix stiffness affects OB function remains unclear.

Materials and methods

We conducted a study that exposed rat primary OBs to polydimethylsiloxane substrates with varied stiffness to investigate the alterations of cell morphology, osteoblastic differentiation and its potential mechanism in mechanotransduction.

Results

Distinctive differences of cell shapes and vinculin expression in rat osteoblasts were detected on different PDMS substrates. As representatives for OB function, expression of alkaline phosphatase, Runx2 and osteocalcin were identified and showed a decrease trend as substrates become soft, which is associated with the Rho/ROCK signalling pathway.

Conclusions

Our results indicated substrate elasticity as a potent regulator in OBs functionalization, which may pave a way for further understanding of bone diseases as well as a potential therapeutic alternative in tissue regeneration.
Team work and cytopathology molecular diagnosis of solid pancreatic lesions
Authors: Fabbri Carlo , Gibiino Giulia , Fornelli Adele , Cennamo Vincenzo , Grifoni Daniela , Visani Michela , Acquaviva Giorgia , Fassan Matteo , Fiorino Sirio , Giovanelli Silvia , Bassi Marco , Ghersi Stefania , Tallini Giovanni , Jovine Elio , Gasbarrini Antonio , de Biase Dario
Published: February 2017

Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of cancer‐associated death in the next decade or so. It is widely accepted that tumorigenesis is linked to specific alterations in key genes and pancreatic neoplasms are some of the best characterized at the genomic level. Recent whole‐exome and whole‐genome sequencing analyses confirmed that PDAC is frequently characterized by mutations in a set of four genes among others: KRAS, TP53, CDKN2A/p16, and SMAD4. Sequencing, for example, is the preferable technique available for detecting KRAS mutations, whereas in situ immunochemistry is the main approach for detecting TP53 gene alteration. Nevertheless, the diagnosis of PDAC is still a clinical challenge, involving adequate acquisition of endoscopic ultrasound (EUS)‐guided fine‐needle aspiration (FNA) and specific pathological assessment from tissue architecture to specific biomolecular tests. The aim of the present review is to provide a complete overview of the current knowledge of the biology of pancreatic cancer as detected by the latest biomolecular techniques and, moreover, to propose a paradigm for strict teamwork collaboration in order to improve the correct use of diagnostic sources.
Lipid‐lowering efficacy and safety of alirocumab in patients with or without diabetes: A sub‐analysis of ODYSSEY COMBO II
Authors: Leiter Lawrence A. , Zamorano José Luis , Bujas‐Bobanovic Maja , Louie Michael J. , Lecorps Guillaume , Cannon Christopher P. , Handelsman Yehuda
Published: February 2017

Aim

This sub‐analysis of the ODYSSEY COMBO II study compared the effects of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in high cardiovascular risk patients with or without diabetes mellitus (DM) receiving maximally tolerated statin therapy.

Methods

COMBO II was a 104‐week, double‐blind study (n = 720) enrolling patients with documented atherosclerotic cardiovascular disease (ASCVD) and baseline LDL‐C ≥70 mg/dL (1.8 mmol/L), and patients without documented ASCVD at high cardiovascular risk with LDL‐C ≥100 mg/dL (2.6 mmol/L). Patients receiving maximally tolerated statin therapy were randomized (2:1) to alirocumab 75 mg every 2 weeks (Q2W; 1 mL subcutaneous injection) or oral ezetimibe 10 mg daily. Alirocumab dose was increased to 150 mg Q2W (also 1 mL) at Week 12 if Week 8 LDL‐C was ≥70 mg/dL.

Results

History of DM was reported in 31% (n = 148) of patients on alirocumab and 32% (n = 77) of patients on ezetimibe. At Week 24, alirocumab consistently reduced LDL‐C from baseline in patients with (−49.1%) or without DM (−51.2%) to a significantly greater extent than ezetimibe (−18.4% and −21.8%, respectively). Occurrence of treatment‐emergent adverse events was similar between groups. Efficacy results at 104 weeks were similar to those at 24 weeks.

Conclusions

Over a 104‐week double‐blind study period, alirocumab provided consistently greater LDL‐C reductions than ezetimibe, with similar LDL‐C results in patients with or without DM. Safety of alirocumab was similar regardless of baseline DM status.
Adhesives based on butyl‐cyanoacrylate for fixation of autologous bone graft: Pilot study in rabbits
Authors: Hochuli‐Vieira Eduardo , Engler Pinto Ana Carolina Basso , Pereira‐Filho Valfrido Antonio , Saska Sybele , Monnazzi Marcelo Silva
Published: February 2017

Background/Aim

Injuries to bone during trauma may require bone grafts and/or fixation to ensure optimal healing. Autologous bone grafts are still very common, but little data exist regarding the most effective means of fixation of such grafts. The aim of this study was to compare the fixation of autologous bone grafts with titanium screws and adhesives based on n‐butyl‐cyanoacrylate.

Material and Methods

Twenty adult rabbits were used. In group I, the graft was fixed with titanium screws (in one side of the animal head), while in groups II and III (in other spots in the same animal head), the graft was fixed with adhesive Tissuacryl® and Histoacryl®, respectively. The animals were sacrificed on post‐operative days 7, 15, 30, 60, and 120. Histological and histomorphometric analyses were performed.

Results

Inflammatory reactions were observed in all groups at 7 days. At 15 days, group I showed no inflammatory reaction. There was new bone formation in group I at 30 days and at 60 days in groups II and III. After 120 days, the grafts were completely incorporated in group I and partially incorporated in groups II and III. Groups II and III presented less graft resorption at the final evaluation: 32.58 (±10.22) and 34.75 (±8.25), compared to 26.58 (±6.48) for group I (P=.001).

Conclusions

The adhesives were compatible when they were in contact with bone structures, and they were effective in fixing the grafts. Groups II and III had less graft resorption.
Characterization of mouthguards: Impact performance
Authors: Guérard Sandra , Barou Jean‐Luc , Petit Julien , Poisson Philippe
Published: February 2017

Background/Aim

It is difficult to characterize the impact behavior of mouthguards on the basis of their components. Impact behavior tests should be performed on mouthguard formed to simulate their intra‐oral performance. The aim of this study was to compare the impact behavior of six models of mouthguards using a standardized experimental protocol.

Material and methods

Four commercially available mouth‐formed mouthguards (SDI™, Gel Nano™, Opro Shield Gold™ and Kipsta R300™), one mouth‐formed mouthguard prototype and one custom‐made mouthguard were tested. The procedures recommended by the manufacturers (injecting procedure for custom‐made mouthguard and “boil‐and‐bite” procedures for mouth‐formed mouthguards) were used to adapt five samples per model on steel jaws. Impact performances were assessed according to labial aspect thickness and maximum contact load (FMax) during impact using a drop tower.

Results

SDI™ and Opro Shield Gold™ had the thinnest labial aspect thickness (P<.01), followed by the Gel Nano™ and the Kipsta R300™ (P<.01) with a thickness of about 3 mm. The prototype and custom‐made mouthguard were thicker (almost 4 mm). The custom‐made mouthguard, the Kipsta R300™ and the prototype had the best impact performances, but the labial aspect thickness of the Kipsta R300™ was significantly lower than that of the custom‐made mouthguard and the prototype. Analysis of force curves and position of the mouthguard on the impacted zone showed that the Kipsta R300™ was less well adapted.

Conclusion

Thickness and impact performance are not sufficient criteria to characterize performance of mouthguards.
Seasonal patterns of downstream movement in partially migratory stream‐dwelling Dolly Varden
Authors: Ayer Christopher G. , Katahira Hirotaka , Fukui Sho , Koizumi Itsuro
Published: February 2017

Migration is a common behaviour among salmonids, but not all individuals within a population migrate, instead becoming residents and remaining in their natal streams. This phenomenon, known as “partial migration,” is well studied among sea‐run and lake‐run populations; however, the lower migratory benefits and costs for mainstem‐run individuals question whether the same mechanisms can be applied for stream‐dwelling salmonids. In this study, we investigated main stem‐run timing and body condition of partially migratory stream‐dwelling Dolly Varden charr (Salvelinus malma) in the Shiisorapuchi River in central Hokkaido, Japan. Based on commonly observed patterns in sea‐run and lake‐run salmonids, we predicted that migration would occur during spring and consist predominantly of age 1 +  females with some small subordinate males. Traps were placed at the mouths of two small tributaries along the Shiisorapuchi River periodically from May to December 2015. Adipose fin samples were taken forDNAto sex the individuals. Consistent to initial predictions, downstream movement occurs only once in the spring, dominated by age‐1 +  females. Trapped fishes (presumed migrants) were slightly longer but slimmer compared to the fish caught in the tributaries (presumed resident), which may be equivalent to smolts in anadromous populations. Regardless of migratory habitat, mechanisms driving partial migration in salmonids may be the same as long as production between natal stream and feeding habitats is significantly different.
Characterization of focal cortical dysplasia with balloon cells by layer‐specific markers: Evidence for differential vulnerability of interneurons
Authors: Nakagawa Julia M. , Donkels Catharina , Fauser Susanne , Schulze‐Bonhage Andreas , Prinz Marco , Zentner Josef , Haas Carola A.
Published: February 2017

Objective

Focal cortical dysplasia (FCD) is a major cause of pharmacoresistant focal epilepsy. Little is known about the pathomechanisms underlying the characteristic cytoarchitectural abnormalities associated with FCD. In the present study, a broad panel of markers identifying layer‐specific neuron subpopulations was applied to characterize dyslamination and structural alterations in FCD with balloon cells (FCD 2b).

Methods

Pan‐neuronal neuronal nuclei (NeuN) and layer‐specific protein expression (Reelin, Calbindin, Calretinin, SMI32 (nonphosphorylated neurofilament H), Parvalbumin, transducin‐like enhancer protein 4 (TLE4), and Vimentin) was studied by immunohistochemistry on paraffin sections of FCD2b cases (n = 22) and was compared to two control groups with (n = 7) or without epilepsy (n = 4 postmortem cases). Total and layer‐specific neuron densities were systematically quantified by cell counting considering age at surgery and brain region.

Results

We show that in FCD2b total neuron densities across all six cortical layers were not significantly different from controls. In addition, we present evidence that a basic laminar arrangement of layer‐specific neuron subtypes was preserved despite the severe disturbance of cortical structure. SMI32‐positive pyramidal neurons showed no significant difference in total numbers, but a reduction in layers III and V. The densities of supragranular Calbindin‐ and Calretinin‐positive interneurons in layers II and III were not different from controls, whereas Parvalbumin‐expressing interneurons, primarily located in layer IV, were significantly reduced in numbers when compared to control cases without epilepsy. In layer VI, the density of TLE4‐positive projection neurons was significantly increased. Altogether, these data show that changes in cellular composition mainly affect deep cortical layers in FCD2b.

Significance

The application of a broad panel of markers defining layer‐specific neuronal subpopulations revealed that in FCD2b neuronal diversity and a basic laminar arrangement are maintained despite the severe disturbance of cytoarchitecture. Moreover, it showed that Parvalbumin‐positive, inhibitory interneurons are highly vulnerable in contrast to other interneuron subtypes, possibly related to the epileptic condition.
Multiplex ligation‐dependent probe amplification as first mutation screening for large deletions and duplications in haemophilia
Authors: Belvini D. , Salviato R. , Radossi P. , Tagariello G.
Published: February 2017

Introduction

Molecular characterization has shown a wide mutational spectrum underlying haemophilia A (HA) and haemophilia B (HB). Different molecular assays have allowed laboratories to perform genetic testing for F8 and F9 mutations.

Aim

Recently, multiplex ligation‐dependent probe amplification (MLPA), a simple technique for relative quantitation of targeted genomic regions, has been introduced in HA and HB for detection of large deletions and duplications. We want to verify if MLPA might be used at the beginning of the molecular investigation.

Methods

We used it to test 22 patients with suspected large deletions, nine patients negative for mutation detection by other methods and finally, 45 new patients as their first screening test.

Results

Carrier status was also established in 28 related females and gross rearrangements were also searched for by MLPA in 19 females with reduced FVIII or FIX levels. All suspected deletions were confirmed apart from two patients. In patients with a negative screening test, MLPA revealed one large duplication, while in two patients where MLPA was used as the first screening step, an exon duplication was detected. In females with reduced FVIII or FIX, no large deletions or duplications were found.

Conclusions

Owing to its simplicity, MLPA seems useful at the beginning of the molecular investigation, saving all the following steps, where positive. Single exon deletion diagnosis requires caution due to the risk of misdiagnosis, but benefits of MLPA appear to overcome the pitfalls.
Comparison of clinical and pathological features of lung lesions of systemic IgG4‐related disease and idiopathic multicentric Castleman's disease
Authors: Terasaki Yasuhiro , Ikushima Soichiro , Matsui Shoko , Hebisawa Akira , Ichimura Yasunori , Izumi Shinyu , Ujita Masuo , Arita Machiko , Tomii Keisuke , Komase Yuko , Owan Isoko , Kawamura Tetsuji , Matsuzawa Yasuo , Murakami Miho , Ishimoto Hiroshi , Kimura Hiroshi , Bando Masashi , Nishimoto Norihiro , Kawabata Yoshinori , Fukuda Yuh , Ogura Takashi ,   the Tokyo Diffuse Lung Diseases Study Group
Published: February 2017

Aims

The lung lesion [immunoglobulin (Ig)G4‐L] of IgG4‐related disease (IgG4‐RD) is a condition that occurs together with IgG4‐RD and often mimics the lung lesion [idiopathic multicentric Castleman's disease (iMCD‐L)] of idiopathic multicentric Castleman's disease (iMCD). Because no clinical and pathological studies had previously compared features of these diseases, we undertook this comparison with clinical and histological data.

Methods and results

Nine patients had IgG4‐L (high levels of serum IgG4 and of IgG4+ cells in lung specimens; typical extrapulmonary manifestations). Fifteen patients had iMCD‐L (polyclonal hyperimmunoglobulinaemia, elevated serum interleukin‐6 levels and polylymphadenopathy with typical lymphadenopathic lesions). Mean values for age, serum haemoglobin levels and IgG4/IgG ratios were higher in the IgG4‐L group and C‐reactive protein levels were higher in the iMCD‐L group. All IgG4‐RD lung lesions showed myxomatous granulation‐like fibrosis (active fibrosis), with infiltration of lymphoplasmacytes and scattered eosinophils within the perilymphatic stromal area, such as interlobular septa and pleura with obstructive vasculitis. All 15 lung lesions of iMCD, however, had marked accumulation of polyclonal lymphoplasmacytes in lesions with lymphoid follicles and dense fibrosis, mainly in the alveolar area adjacent to interlobular septa and pleura without obstructive vasculitis.

Conclusions

Although both lesions had lymphoplasmacytic infiltration, lung lesions of IgG4‐RD were characterized by active fibrosis with eosinophilic infiltration within the perilymphatic stromal area with obstructive vasculitis, whereas lung lesions of iMCD had lymphoplasmacyte proliferating lesions mainly in the alveolar area adjacent to the perilymphatic stromal area. These clinicopathological features may help to differentiate the two diseases.
Resilient practices of consumption in times of crisis—Biographical interviews with members of vulnerable households in Germany
Authors: Boost Marie , Meier Lars
Published: February 2017

This article analyzes the impact of different consumption patterns that are used to counteract economic hardship and to mitigate the effects of such hardship in times of crisis in Germany. We focus on resilient socioeconomic practices, such as the development of formal or informal practices of consumption, production, and saving. We develop a critical approach of social resilience that is combined with the idea of a bricolage (Levi‐Strauss, 1962) of “mixed economy” practices (Malcolmson, 1988). This is done by demonstrating the relevance of preconditions for resilient practices. Based on an analysis of in‐depth biographical interviews, two main types of resilient consumption practices and strategies of those who experience economic hardship are identified. First, saving, as the predominant practice, includes buying low‐priced items at discount stores, taking advantage of the offerings of charity organisations, and reducing expenditures overall. Second, home production consists of subsistence farming or do‐it‐yourself activities for personal use or bartering. In this context, particular attention is paid to the reactivation of traditional noncommodified practices, such as the nonmonetary (mutual) exchange of goods and services within social networks, and the reactivation of previously undervalued knowledge that results in new spheres of production. We conclude by discussing the relevance of preconditions and consequences—as well as the demands and personal costs—of the resilient practices used.
Inflammatory stress of pancreatic beta cells drives release of extracellular heat‐shock protein 90α
Authors: Ocaña Gail J. , Pérez Liliana , Guindon Lynette , Deffit Sarah N. , Evans‐Molina Carmella , Thurmond Debbie C. , Blum Janice S.
Published: February 2017

A major obstacle in predicting and preventing the development of autoimmune type 1 diabetes (T1D) in at‐risk individuals is the lack of well‐established early biomarkers indicative of ongoing beta cell stress during the pre‐clinical phase of disease. Recently, serum levels of the α cytoplasmic isoform of heat‐shock protein 90 (hsp90) were shown to be elevated in individuals with new‐onset T1D. We therefore hypothesized that hsp90α could be released from beta cells in response to cellular stress and inflammation associated with the earliest stages of T1D. Here, human beta cell lines and cadaveric islets released hsp90α in response to stress induced by treatment with a combination of pro‐inflammatory cytokines including interleukin‐1β, tumour necrosis factor‐α and interferon‐γ. Mechanistically, hsp90α release was found to be driven by cytokine‐induced endoplasmic reticulum stress mediated by c‐Jun N‐terminal kinase (JNK), a pathway that can eventually lead to beta cell apoptosis. Cytokine‐induced beta cell hsp90α release and JNK activation were significantly reduced by pre‐treating cells with the endoplasmic reticulum stress‐mitigating chemical chaperone tauroursodeoxycholic acid. The hsp90α release by cells may therefore be a sensitive indicator of stress during inflammation and a useful tool in assessing therapeutic mitigation of cytokine‐induced cell damage linked to autoimmunity.
CD21intCD23+ follicular B cells express antigen‐specific secretory IgM mRNA as primary and memory responses
Authors: Meng Qing‐Hai , White Harry N.
Published: February 2017

CD21int CD23+ IgM+ mouse follicular B cells comprise the bulk of the mature B‐cell compartment, but it is not known whether these cells contribute to the humoral antibody response. We show using a direct RT‐PCR method for antigen‐specific VH, that FACS‐sorted mouse CD21int CD23+ B cells express specific secretory IgM VH transcripts in response to immunization and also exhibit a memory response. The secretory IgM expressed is distinct from the IgG expressed by cells of this phenotype, which we also analyse here, having a distinct broader distribution of CDR‐H3 sequences and zero or low levels of somatic mutation in the region analysed. These results imply that cells of the CD21int CD23+ phenotype have distinct IgM+ and IgG+ populations that contribute directly to the humoral antibody and memory responses by expressing antigen‐specific secretory immunoglobulin. We also argue that the more diverse CDR‐H3 sequences expressed by antigen‐experienced IgM+ CD21int CD23+ follicular B cells would place them at the bottom of a recently hypothesized memory B‐cell hierarchy.
Increased CTLA‐4+ T cells may contribute to impaired T helper type 1 immune responses in patients with chronic obstructive pulmonary disease
Authors: Tan Dino B. A. , Teo Teck‐Hui , Setiawan Abdul M. , Ong Nathanael E. , Zimmermann Maja , Price Patricia , Kirkham Lea‐Ann S. , Moodley Yuben P.
Published: February 2017

Impaired T helper type 1 (Th1) function is implicated in the susceptibility of patients with chronic obstructive pulmonary disease (COPD) to respiratory infections, which are common causes of acute exacerbations of COPD (AECOPD). To understand the underlying mechanisms, we assessed regulatory T (Treg) cells and the expression of an inhibitory T‐cell receptor, cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4). Cryopreserved peripheral blood mononuclear cells (PBMC) from patients with AECOPD (n = 17), patients with stable COPD (sCOPD; n = 24) and age‐matched healthy non‐smoking controls (n = 26) were cultured for 24 hr with brefeldin‐A or monensin to detect intracellular or surface CTLA‐4 (respectively) by flow cytometry. T cells in PBMC from AECOPD (n = 9), sCOPD (n = 14) and controls (n = 12) were stimulated with anti‐CD3 with and without anti‐CTLA‐4 blocking antibodies and cytokines were quantified by ELISA. Frequencies of circulating T cells expressing intracellular CTLA‐4 were higher in sCOPD (P = 0·01), whereas patients with AECOPD had more T cells expressing surface CTLA‐4 than healthy controls (P = 0·03). Increased frequencies of surface CTLA‐4+ CD4+ T cells and CTLA‐4+ Treg cells paralleled increases in plasma soluble tumour necrosis factor receptor‐1 levels (r = 0·32, P = 0·01 and r = 0·29, P = 0·02, respectively) in all subjects. Interferon‐γ responses to anti‐CD3 stimulation were inversely proportional to frequencies of CD4+ T cells expressing intracellular CTLA‐4 (r = −0·43, P = 0·01). Moreover, CTLA‐4 blockade increased the induction of interferon‐γ, tumour necrosis factor‐α and interleukin‐6 in PBMC stimulated with anti‐CD3. Overall, chronic inflammation may expand sub‐populations of T cells expressing CTLA‐4 in COPD patients and therefore impair T‐cell function. CTLA‐4 blockade may restore Th1 function in patients with COPD and so aid the clearance of bacterial pathogens responsible for AECOPD.
Priming with high and low respiratory allergen dose induces differential CD4+ T helper type 2 cells and IgE/IgG1 antibody responses in mice
Authors: Furuhashi Kazuki , Chua Yen L. , Wong Kenneth H. S. , Zhou Qian , Lee Debbie C. P. , Liong Ka H. , Teo Guo H. , Hutchinson Paul E. , Kemeny David M.
Published: February 2017

Sensitization of allergic patients normally takes place over several years and is the result of repeated exposure to low levels of allergen. Most mouse asthma models use a high dose of allergen administered over a short period. We have investigated the role of dose in the immune response to an inhaled respiratory allergen (Blomia tropicalis). We observed the effect of priming dose on the allergic response in mice intranasally immunized with low (0·5 μg) and high (50 μg) doses of B. tropicalis extract and killed 1 day after the last challenge. For both doses of allergen, T helper type 2 (Th2) cells and Th2 cytokines were evident as well as eosinophilic inflammation accompanied by mucus hyper‐secretion. By contrast, IgE and IgG1 antibody responses were normally only detected at high‐dose priming. To investigate the mechanism for these effects, we found group 2 innate lymphoid cells (ILC2s) were increased 48 hr after challenge in the low‐dose‐treated but not the high‐dose‐treated mice. Furthermore, we determined whether repeated low‐dose exposure with different priming protocols could induce an antibody response. Repeated low‐dose exposure to 0·5 μg three times weekly for 4 weeks (cumulative 6 μg) had the same effect as a shorter high‐dose exposure (cumulative 80 μg) and increasing cumulative dose induced antibody responses. These data indicate that low doses of allergen are sufficient to prime Th2 cells and ILC2s, but insufficient to induce antibody responses. Cumulative exposure to small amounts of allergen induces both Th2 and antibody responses and may better reflect natural sensitization.
CD4+ CD25+ GARP+ regulatory T cells display a compromised suppressive function in patients with dilated cardiomyopathy
Authors: Wei Yuzhen , Yu Kunwu , Wei Hui , Su Xin , Zhu Ruirui , Shi Huairui , Sun Haitao , Luo Quan , Xu Wenbin , Xiao Junhui , Zhong Yucheng , Zeng Qiutang
Published: February 2017

Dilated cardiomyopathy (DCM) is a lethal inflammatory heart disease and closely connected with dysfunction of the immune system. Glycoprotein A repetitions predominant (GARP) expressed on activated CD4+ T cells with suppressive activity has been established. This study aimed to investigate the frequency and function of circulating CD4+ CD25+ GARP+ regulatory T (Treg) cells in DCM. Forty‐five DCM patients and 46 controls were enrolled in this study. There was a significant increase in peripheral T helper type 1 (Th1) and Th17 number and their related cytokines [interferon‐γ (IFN‐γ), interleukin (IL‐17)], and an obvious decrease in Treg number, transforming growth factor‐β1 (TGF‐β1) levels and the expression of forkhead box P3 (FOXP3) and GARP in patients with DCM compared with controls. In addition, the suppressive function of CD4+ CD25+ GARP+ Treg cells was impaired in DCM patients upon T‐cell receptor stimulation detected using CFSE dye. Lower level of TGF‐β1 and higher levels of IFN‐γ and IL‐17 detected using ELISA were found in supernatants of the cultured CD4+ CD25+ GARP+ Treg cells in DCM patients compared with controls. Together, our results indicate that CD4+ CD25+ GARP+ Treg cells are defective in DCM patients and GARP seems to be a better molecular definition of the regulatory phenotype. Therefore, it might be an attractive stategy to pay more attention to GARP in DCM patients.
Do professional boundaries limit trust?
Authors: Smythe Elizabeth , Hennessy Julia , Abbott Max , Hughes Frances
Published: February 2017

The present study uses stories of mental health support workers talking about their relationship with clients to wonder about how trust might be limited by the professional boundaries of nursing. The writing arose out of an appreciative inquiry study looking at the role of mental health support workers. Participants talked about how they worked with their clients. As researchers, we were struck by the depth of trust that was built between worker and client. We have brought a phenomenological lens to wonder about the nature of trust, as shown in the data. The original research sought to identify what was working well for mental health support workers. The present study brings a phenomenological interpretive approach to four stories from the discovery phase of the study, with our thinking informed by Heidegger and van Manen. Interviews were conducted with 26 mental health support workers and six stakeholders in 2012–2103. For this paper, we drew from those transcripts stories of three mental health support workers and one stakeholder. Through a process of talking together, writing, and rewriting, we wondered about the meaning within these stories, with a strong focus on how trust was enacted. We saw that mental health support workers in this study, by not carrying the boundaries of being ‘professional’, seemed free to grow a stronger relationship of trust which was therapeutic. We ask: Is it time to rethink how professional boundaries limit the level of trust achieved with clients to the detriment of impactful care?
A systematic review of the psychometric properties of instruments for assessing the quality of the physical environment in healthcare
Authors: Elf Marie , Nordin Susanna , Wijk Helle , Mckee Kevin J.
Published: February 2017

Aim

To identify instruments measuring the quality of the physical healthcare environment, describe their psychometric properties.

Background

The physical healthcare environment is regarded as a quality factor for health care. To facilitate evidence‐based design there is a need for valid and usable instruments that can evaluate the design of the healthcare environment.

Design

Systematic psychometric review.

Data sources

A systematic literature search in Medline, CINAHL, Psychinfo, Avery index and reference lists of eligible papers (1990–2016).

Review method

Consensus based standards for selection of health measurement instruments guidelines were used to evaluate psychometric data reported.

Results

Twenty‐three instruments were included. Most of the instruments are intended for healthcare environments related to the care of older people. Many of the instruments were old, lacked strong, contemporary theoretical foundations, varied in the extent to which they had been used in empirical studies and in the degree to which their validity and reliability had been evaluated.

Conclusions

Although we found many instruments for measuring the quality of the physical healthcare environment, none met all of our criteria for robustness. Of the instruments, The Multiphasic environmental assessment procedure, The Professional environment assessment protocol and The therapeutic environment screening have been used and tested most frequently. The Perceived hospital quality indicators are user centred and combine aspects of the physical and social environment. The Sheffield care environment assessment matrix has potential as it is comprehensive developed using a theoretical framework that has the needs of older people at the centre. However, further psychometric and user‐evaluation of the instrument is required.
Underemployment among mothers of children with intellectual disabilities
Authors: Chou Yueh‐Ching , Kröger Teppo , Pu Cheng‐yun
Published: February 2017

Background

Mothers with lifelong care responsibilities might involuntarily be non‐employed or work part‐time, both of which are defined as “underemployment.” This study aimed to investigate who these underemployed mothers are and what are the factors associated with such employment hardship when having a child with intellectual disability (ID).

Method

An interview survey was conducted in 2011 in two local authorities of Taiwan on 876 working‐age mothers with a child with intellectual disability; 514 of them were working part‐time/non‐employed and chosen as participants of this study.

Results

The mothers with a younger child with intellectual disability, a higher level of education, a lower level of family income and more family members with disabilities were more likely to be underemployed compared with the mothers who were voluntarily working part‐time/non‐employed.

Conclusions

The underemployed mothers were more likely to have financial difficulty and heavy caregiving loads; their employment hardship should be of concern for policymakers.
Variability in stable isotopes of snowy owl feathers and contribution of marine resources to their winter diet
Authors: Robillard Audrey , Gauthier Gilles , Therrien Jean‐François , Fitzgerald Guy , Provencher Jennifer F. , Bêty Joël
Published: February 2017

The snowy owl is an elusive arctic predator known for its nomadic behaviour. Satellite tracking has revealed that some adult snowy owls could make an extensive use of the marine environment during the non‐breeding season. However, the relative contribution of marine resources to their diet is unknown. Stable isotope analyses can be useful to document the diet of mobile animals during periods of the year when individuals are less accessible. This study aimed to assess variation in isotopic values (δ13C and δ15N) of various feather types, and the usefulness of feathers to determine the contribution of the marine environment to the winter diet of snowy owls captured in summer. We sampled feathers coming from 6 body regions of 18 breeding females at two sites in the eastern Canadian Arctic in 2013 and 2014. Prior to analyses, diet‐tissue discrimination factors of snowy owl feathers were established in captivity. Variability in isotopic values among feather types was relatively low and pairwise correlations in isotopic values between feathers on the same individual were variable and often low, which suggests differences in the diet at the time when various feathers were synthesized. Diet reconstruction models detected a contribution of marine sources to snowy owl feathers ranging from 4 to 19% among feather types. However, the marine contribution was highly variable when single feathers were examined within individuals, ranging from 3 to 71%. This indicated that no single feather type could be used alone to reliably infer the contribution of marine resources to the winter diet of owls, possibly due to a high variability in the timing and sequence of molt. For asynchronous molters like snowy owls, we recommend sampling multiple feathers from various body regions, excluding wing feathers, to investigate winter diet or habitat use.
The effect of host vicariance and parasite life history on the dispersal of the multi‐host ectoparasite, Hyalomma truncatum
Authors: Sands Arthur F. , Apanaskevich Dmitry A. , Matthee Sonja , Horak Ivan G. , Matthee Conrad A.
Published: February 2017

Aim

It is predicted that the dispersal and gene flow of ectoparasites with wide host ranges are correlated with the vagilities of their most mobile hosts. To test this, the phylogeographical structure of a widespread generalist tick occurring on large ungulates was determined and compared with previously published host patterns.

Location

Africa.

Methods

mtDNA cytochrome c oxidase subunit I (COI) sequences were generated for 182 Hyalomma truncatum specimens sampled from 21 Afrotropical localities. A subsample of these was sequenced for the nuclear Histone 3 (H3) and Calreticulin (CRT) regions. Phylogeographical inferences were made by using haplotype networks, a Bayesian analysis of population structure, isolation by distance (IBD) and a Bayesian gene tree. Demographic changes in the populations were determined with Bayesian skyline plots.

Results

Two highly divergent geographically confined mtDNA clades were detected, and these were partly supported by significant differentiation at nuclear DNA level. The clades differ by 9.88% (± 0.40%) mtDNA COI sequence divergence. The southern African clade, which expanded approximately 100 ka, shows no geographical barriers to dispersal and also no IBD. The northern African clade shows signs of IBD, at least five distinct genetic subgroups and an earlier expansion at 200 ka.

Conclusion

The phylogeography of the generalist tick is broadly congruent with host vicariance and supports the previously defined African Pleistocene savanna refugia. The magnitude of the sequence divergence between geographically separated genetic lineages suggests that H. truncatum comprises two distinct yet undescribed species. The dispersal of ectoparasites with wide host ranges is dependent on the ability of the various life stages of the parasite to survive in the off‐host environment coupled to host movement.
The matrix effect: how agricultural matrices shape forest fragment structure and amphibian composition
Authors: Ferrante Lucas , Baccaro Fabricio Beggiato , Ferreira Eric Batista , Sampaio Maria Fernanda de Oliveira , Santos Thays , Justino Rodrigo Cesário , Angulo Ariadne
Published: February 2017

Aim

Habitat loss and fragmentation are considered the main drivers of species population declines and extinctions in the world. The large‐scale replacement of natural habitats with human‐modified habitats, such as the replacement of forests with agricultural and livestock farming areas, creates a scenario where natural habitat patches are immersed in an inhospitable land use matrix. We sought to evaluate how forest fragments (FFs) are influenced by the different surrounding landscape components, where we assessed how agricultural matrices that differ in structure and seasonality affect the structure of FFs and their amphibian assemblages.

Location

Atlantic Forest, Brazil.

Methods

Using diverse methods including satellite imagery, historical land use and field data, we evaluated the effects of representative agricultural matrices on the structure of FFs and their amphibian composition, species richness and abundance.

Results

Our results suggest that the structure of FFs and amphibian composition, species richness and individual abundance are intimately linked to the type of matrix and its proportion around FFs. The nature of the matrix is more likely to affect species richness, individual abundance and composition of amphibian assemblages than FF size, reducing the species‐area relationship in FFs. There is strong support for the hypothesis that certain agricultural matrices facilitate FF exposure to the elements and a decrease in forest integrity within the fragment, which is reflected in a loss of strict forest inhabitants. Those matrices that allow for a greater exposure of FFs also appear to favour their occupation by habitat generalists.

Main conclusions

Surrounding matrices affect the structure and dynamics of forest remnants and should therefore be considered in management plans of severely fragmented landscapes. The influence of the land matrix should be urgently assessed, as it has effects on species occurrences and distribution. This is especially relevant considering the increasing deforestation rates in biodiversity hotspots world‐wide.
Evolutionary flexibility in five hummingbird/plant mutualistic systems: testing temporal and geographic matching
Authors: Abrahamczyk Stefan , Poretschkin Constantin , Renner Susanne S.
Published: February 2017

Aim

Partners in co‐evolutionary interactions must be ecologically interdependent and at least at some stage have matching traits and more or less overlapping ranges. As co‐evolution is a process, neither the mutual dependence nor the trait and range matching are expected to be static or perfect. Here we investigate the extent of evolutionary flexibility in tight pollination mutualisms between hummingbirds and plants, ranging from straight‐billed species to sicklebills.

Location

The Americas.

Methods

The five considered pollination mutualisms are between the following hummingbird and plant species: Calypte anna and Ribes speciosum (Grossulariaceae); Basilinna xantusii and Arbutus peninsularis (Ericaceae); two species of Sephanoides and Tristerix aphyllus/corymbosus (Loranthaceae); two species of Eutoxeres and 34 species of curved‐corolla Centropogon (Campanulaceae); and six species of Oreotrochilus and seven species of Chuquiraga (Asteraceae). While ecological interdependence and trait matching in these mutualisms are well established, geographic occurrence data and molecular clock‐based ages for the 10 clades were newly compiled.

Results

We found matching bird and plant stem ages in two of the five systems and (much) older bird than plant ages in the other three. The implied adaptation of plant populations to already existing hummingbird species fits with the modelled distributions. In three of the systems, the ranges of the plants overlap those of their pollinators by > 90%; conversely, the range overlap between the bird species and the plant species they pollinate is much less than that. Surprisingly, the age mismatch was greatest in the Eutoxeres/Centropogon system, in spite of the perfect morphological fit among bills and corollas, illustrating the evolutionary flexibility of these mutualisms and the apparently rapid ‘addition’ of further plant species.

Main conclusions

These findings illuminate the macroevolutionary assembly of hummingbird/plant mutualisms, which has been highly dynamic, even in specialized systems with perfect morphological trait fitting.
Elevated PRC1 in gastric carcinoma exerts oncogenic function and is targeted by piperlongumine in a p53‐dependent manner
Authors: Zhang Bin , Shi Xiaoting , Xu Guifang , Kang Wei , Zhang Weijie , Zhang Shu , Cao Yu , Qian Liping , Zhan Ping , Yan Hongli , To Ka Fai , Wang Lei , Zou Xiaoping
Published: February 2017

Gastric carcinoma is one of the most common malignancies worldwide and the second most frequent cause of cancer‐related death in China. Protein regulator of cytokinesis 1 (PRC1) is involved in cytokinesis and plays key roles in microtubule organization in eukaryotes. This study was aimed to analyse the expression and to investigate the functional role of PRC1 in gastric tumorigenesis. The expression of PRC1 was evaluated by qRT‐PCR, Western blot and immunohistochemistry. The biological function of PRC1 was determined by CCK‐8 proliferation assays, monolayer colony formation, xenografted nude mice and cell invasion assays by shRNA‐mediated knockdown in AGS and HGC27 cells. The regulation of PRC1 expression by piperlongumine was also investigated using dual‐luciferase reporter assay and ChIP‐qPCR analysis. PRC1 was up‐regulated in primary gastric cancers. Overexpression of PRC1 in gastric cancers was associated with poor disease‐specific survival and overall survival. PRC1 knockdown in AGS and HGC27 cell lines suppressed proliferation, reduced monolayer colony formation, inhibited cell invasion and migration ability and induced cell‐cycle arrest and apoptosis. Inhibition of PRC1 also suppressed tumour growth in vivo. We finally confirmed that PRC1 is a novel downstream target of piperlongumine in gastric cancer. Our findings supported the oncogenic role of PRC1 in gastric carcinogenesis. PRC1 might serve as a prognostic biomarker and potential therapeutic target for gastric carcinoma.
Effect of ridge preservation for early implant placement – is there a need to remove the biomaterial?
Authors: Thoma Daniel S. , Naenni Nadja , Benic Goran I. , Muñoz Fernando , Hämmerle Christoph H. F. , Jung Ronald E.
Published: February 2017

Aim

To assess (i) bone regeneration around implants placed early in sites with or without ridge preservation and (ii) if the bone substitute material (DBBM‐C) has to be removed at implant placement.

Materials and methods

In eight beagle dogs, three sites were randomly assigned to ridge preservation (DBBM‐C plus collagen matrix (CMX)) (two sites; RP) or spontaneous healing (1 site; SH). Four weeks later, in one of the RP sites, dental implants were placed without removing the DBBM‐C (RP1), whereas in RP2 and SH sites all non‐integrated DBBM‐C and/or granulation tissue were removed before implant placement and concomitant GBR. Histomorphometric outcomes were assessed at 4 and 12 weeks.

Results

The median buccal fBIC (first bone‐to‐implant contact) was located more apical in groups RP1: 1.34 mm (0.09; 2.96) and RP2: 1.41 mm (0.54; 2.72) than in group SH: 0.79 mm (0.26; 1.50) (p = 0.452) at 4 weeks. At 12 weeks, median buccal fBIC values were for RP1: 0.88 mm (0.00; 2.33), for RP2: 0.16 mm (0.00; 1.33) and for SH: 0.00 mm (0.00; 0.98) (p = 0.362). BIC values increased over 12 weeks in all groups.

Conclusions

Ridge preservation followed by early implant placement led to higher BIC values at 12 than at 4 weeks. There is no need to remove the biomaterial at implant placement to ensure osseointegration. No relevant differences were observed between the three groups for any outcome measure.
Chemokine in inflamed periodontal tissues activates healthy periodontal‐ligament stem cell migration
Authors: Lee Jung‐Seok , Lee Jong‐Bin , Cha Jae‐Kook , Choi Eun‐Young , Park So‐Yon , Cho Kyoo‐Sung , Kim Chang‐Sung
Published: February 2017

Aim

The present study aimed to characterize the expression pattern of chemokines obtained from inflamed periodontal defects and to determine the characteristics of human periodontal‐ligament stem cells (hPDLSCs) migrated by each specific chemokine.

Materials and Methods

Both inflamed and healthy periodontal tissues were obtained from periodontitis patients (n = 11), and the chemokine expression levels were analyzed. The periodontal‐tissue‐specific chemokines were applied to healthy hPDLSCs from extracted teeth (n = 3), with FGF‐2 acting as a positive control. Cells were separated by selected chemokines using transwell method into migrated/unmigrated hPDLSCs. The characteristics of the hPDLSC subpopulation recruited by each chemokine were assessed, and gene expression pattern was analyzed by microarray.

Results

Chemokines were categorized into three groups by specific patterns of “appearing,” “increasing,” and “decreasing/disappearing” from healthy to inflamed tissues. A representative chemokine from each group enhanced the capacities for colony formation and osteogenic/adipogenic differentiation while maintaining the surface markers of hPDLSCs. RANTES/CCL5 significantly increased the cellular migration of hPDLSCs, via enhancement of signaling pathways, regulation of the actin skeleton, and focal adhesion.

Conclusion

The present study found a specific chemokine profile induced by inflammation in periodontal tissues, with RANTES/CCL5 appearing to play a role in the migration of hPDLSCs into inflammatory periodontal lesions.