bluuebunny/crossref_metadata_2025 huggingface dataset:
CNS microstructure in the wandering wolf spider Arctosa kwangreungensis (Araneae: Lycosidae)
Authors: Yang Sung‐Chan , Moon Myung‐Jin
Published: March 2015

The supraesophageal ganglion of the wolf spider Arctosa kwangreungensis is made up of a protocerebral and tritocerebral ganglion, whereas the subesophageal ganglionic mass is composed of a single pair of pedipalpal ganglia, four pairs of appendage ganglia, and a fused mass of abdominal neuromeres. In the supraesophageal ganglion, complex neuropile masses are located in the protocerebrum which include optic ganglia, the mushroom bodies, and the central body. Characteristically, the only nerves arising from the protocerebrum are the optic nerves, and the neuropiles of the principal eyes are the most thick and abundant in this wandering spider. The central body which is recognized as an important association center is isolated at the posterior of the protocerebrum and appears as a complex of highly condensed neurons. These cells give off fine parallel bundles of axons arranged in the mushroom bodies. The subesophageal nerve mass can be divided into two main tracts on the basis of direction of the neuropiles. The dorsal tracts are contributed to from the motor or interneurons of each ganglion, whereas the ventral tracts are from incoming sensory axons.
Plaque Thrombosis is Reduced by Attenuating Plaque Inflammation with Pioglitazone and is Evaluated by Fluorodeoxyglucose Positron Emission Tomography
Authors: Zhang Ming‐Duo , Zhao Xue‐Cheng , Zhang Yu‐Hui , Yan Yun‐Feng , Wang Zheng‐Ming , Lv Shu‐Zheng , Zhao Quan‐Ming
Published: March 2015

Introduction

The relationship between the beneficial effects of pioglitazone in reducing clinical events and plaque inflammatory burden remains unknown. This study aimed to determine whether pioglitazone can reduce the number of plaque thrombosis incidences and whether decreasing plaque inflammation is the mechanism by which pioglitazone reduces plaque thromboses.

Methods and Results

therosclerotic rabbits were divided into two groups: the atherosclerosis group (n = 13) and pioglitazone group (n = 10). The rabbits underwent pharmacological triggering to induce thrombosis. Serum inflammatory markers, FDG uptake, macrophage, and neovessel staining detected arterial inflammation. PET/CT scans were performed twice (baseline and posttreatment scans). Plaque area, macrophages, and neovessels were measured and the histologic sections were matched with the PET/CT scans. Serum MMP‐9 and hsCRP were lower in the pioglitazone group compared to the atherosclerosis group. The SUVmean significantly decreased in the pioglitazone group (0.62 ± 0.21 vs. 0.55 ± 0.19, P = 0.008), but increased in the atherosclerosis group (0.61 ± 0.15 vs. 0.91 ± 0.20, P < 0.000). The incidence rate of plaque rupture, plaque area, macrophage density, and neovessel density was significantly lower in rabbits with pioglitazone than without (15% vs. 38%, P < 0.001; 18.00 ± 2.30 vs. 27.00 ± 1.60; P < 0.001; 8.80 ± 3.94 vs. 28.26 ± 2.49; P < 0.001; 16.50 ± 3.09 vs. 29.00 ± 2.11; P < 0.001, respectively). Moreover, plaque area and macrophage density were positively correlated with SUV values.

Conclusions

Our study suggests that pioglitazone can reduce the number of plaque thrombosis incidences by decreasing plaque inflammation. 18F‐FDG‐PET/CT can detect plaque inflammation and assess the effects of antiatherosclerotic drugs.
Resilience metrics to inform ecosystem management under global change with application to coral reefs
Authors: Mumby Peter J. , Anthony Kenneth R. N.
Published: March 2015

Environmental policy instruments often require that natural resource managers safeguard the resilience of ecosystems. However, ‘resilience’ has been a difficult concept to operationalise. Two forms of resilience are recognised in the ecological literature. ‘Ecological resilience’ concerns ecosystems that possess alternative equilibrial states (attractors) and has been operationalised in a few systems. ‘Engineering resilience’ was developed for ecosystems with a single attractor, but its use is confined to systems that gravitate towards a stable equilibrium.

We present a general method to quantify engineering resilience that can be applied irrespective of an ecosystem's stability or proclivity to obey multiple attractors. The technique uses a system model to distinguish the effects of globally driven (and essentially unmanageable) stressors, such as climate change and ocean acidification, from regional‐ and local‐scale (manageable) stressors on the ecosystem.

We illustrate the technique using a simple coral reef model and find it able to calculate the impacts of managing crown‐of‐thorns starfish against a background of increasing stress from climate change and ocean acidification.

Resilience analyses using our approach help assess the relative importance of local‐ or regional‐scale management interventions under varying degrees of global environmental change, even if they preside over long‐term ecosystem decline. Several frameworks of varying complexity are provided to guide the linkage of resilience metrics to environmental decision‐making.
Quantifying physiological influences on otolith microchemistry
Authors: Sturrock Anna M. , Hunter Ewan , Milton J. Andrew ,   EIMF, Johnson Rachel C. , Waring Colin P. , Trueman Clive N.
Published: March 2015

Trace element concentrations in fish earstones (‘otoliths’) are widely used to discriminate spatially discrete populations or individuals of marine fish, based on a commonly held assumption that physiological influences on otolith composition are minor, and thus variations in otolith elemental chemistry primarily reflect changes in ambient water chemistry.

We carried out a long‐term (1‐year) experiment, serially sampling seawater, blood plasma and otoliths of mature and immature European plaice (Pleuronectes platessa L.) to test relationships between otolith chemistry and environmental and physiological variables.

Seasonal variations in otolith elemental composition did not track seawater concentrations, but instead reflected physiological controls on metal transport and biokinetics, which are likely moderated by ambient temperature. The influence of physiological factors on otolith composition was particularly evident in Sr/Ca ratios, the most widely used elemental marker in applied otolith microchemistry studies. Reproduction also triggered specific variations in otolith and blood plasma metal chemistry, especially Zn/Ca ratios in female fish, which could potentially serve as retrospective spawning indicators.

The influence of physiology on the trace metal composition of otoliths may explain the success of microchemical stock discrimination in relatively homogenous marine environments, but could complicate alternative uses for trace element compositions in biominerals of higher organisms.
Clinical and image improvement of Raynaud's phenomenon after botulinum toxin type A treatment
Authors: Zhao HongMei , Lian YaJun
Published: March 2015

Raynaud's phenomenon is often accompanied by pain, digital ulceration and compromised daily activities. Pharmacological therapy or sympathectomies have been administered to diminish these symptoms but existing treatments are not invariably efficacious. A recent case series has described the use of botulinum toxin type A in the treatment of Raynaud's phenomenon. We report two patients with severe or mild Raynaud's phenomenon who were injected with BTX‐A; both of whom experienced clinical and image improvement after treatment.
Sarcoidosis presenting as non‐scarring non‐scalp alopecia
Authors: Dan Luke , Relic John
Published: March 2015

In this article we describe a 39‐year‐old man who presented with non‐scarring non‐scalp alopecia of his limbs as the initial presentation of sarcoidosis. Alopecia is a rare cutaneous manifestation of sarcoidosis. A literature review has found only one other example of sarcoidosis presenting as non‐scarring non‐scalp alopecia in an area other than the scalp in a patient who was otherwise asymptomatic. Several reported cases have described scarring alopecia of the scalp, which is the area of skin most commonly affected by sarcoidosis. There has been one documented case of sarcoidosis manifesting as total body non‐scarring alopecia in a patient who had systemic symptoms of sarcoidosis. Other cases have presented rare cutaneous manifestations of sarcoidosis but in all these cases several other organ systems have been involved, and the patient has had systemic symptoms on presentation or the cutaneous presentation did not include non‐scalp non‐scarring alopecia.
Factors contributing to poor treatment outcomes in childhood atopic dermatitis
Authors: Sokolova Anna , Smith Saxon D
Published: March 2015

Atopic dermatitis (AD) is a chronic relapsing inflammatory disease of the skin and is the most common paediatric dermatological condition. While no cure is available, it can be treated effectively if adherence to a therapeutic plan is maintained. Poor adherence to treatment is common in AD and can lead to treatment failure, which has significant impacts on the patient, family and society. A comprehensive literature search was conducted to identify factors that contribute to poor treatment adherence in childhood AD and to identify possible strategies to remedy these. Identified factors leading to poor treatment adherence include: complexity of treatment regimen, lack of knowledge, impaired quality of life, dissatisfaction with treatment strategies, infrequent follow up, corticosteroid phobia and the use of complementary and alternative medicine. Effective strategies to increase treatment adherence include: caregiver education and utilisation of education adjuncts, optimisation of the patient/caregiver–clinician relationship, early and frequent follow up and improvement of patient and caregiver quality of life.
Assessment of attitudes towards sun‐protective behaviour in Australians: A cross‐sectional study
Authors: Garbutcheon‐Singh Kieran B , Dixit Shreya , Lee Andrew , Brown Pam , Smith Saxon D
Published: March 2015

Objective

To assess the knowledge, attitudes and behaviour towards sun protection measures in a sample of Australian adults.

Methods

A multicentre, cross‐sectional study was undertaken during 2014 using a population‐based survey of 416 individuals over the age of 18. The knowledge, behaviour and attitudes towards sun protection measures in this group of adults were assessed. The impact of educational level and employment status on responses was also evaluated.

Results

Sunscreen is the most common sun‐protective measure. Daily sunscreen use is below 20%. Forgetfulness was the largest barrier to sunscreen use. A total of 85% of respondents did not apply a sufficient amount of sunscreen. Only 32% of individuals reapplied sunscreen every 2 hours and 20% never reapplied it. In the preceding year, one or more sun burns were suffered by 46% of the participants in the survey. In all, 36% of individuals rarely or never check their sunscreens expiry date and less than 50% of individuals replaced their sunscreen each year. Furthermore, 65% were unaware that sunscreens stored above 25°C were less effective than when stored correctly as per manufactures labelling.

Conclusions

This study highlights a number of significant deficiencies that future sun‐protection programmes could target in order to improve the general public's knowledge and attitudes towards sun protection. There is also a need for this to be translated into the public's sun‐protection behaviour.
Social exclusion influences attentional bias to social information
Authors: Xu Mengsi , Li Zhiai , Zhang Junhua , Sun Lijing , Fan Lingxia , Zeng Qinghong , Yang Dong
Published: March 2015

Using three experiments, the present study investigates the impact of social exclusion on attention. Specifically, we investigate whether social exclusion promotes attentional bias to social acceptance cues (smiling faces) or social exclusion cues (angry faces) among an Asian population. The Cyberball game was adopted to manipulate social inclusion or exclusion, and a dot‐probe task was used to measure individuals' responses to smiling or angry faces. In Experiments 1 and 2, each trial consisted of either a smiling or angry face that was paired with a neutral face. In Experiment 1, when the stimulus onset‐asynchronies (SOA) were 500 ms, the inhibition of return emerged, indirectly indicating that social exclusion promotes sensitivity to social acceptance cues. In Experiment 2, after setting the SOA to 200 ms, we found that social exclusion promotes attentional bias to smiling faces compared to neutral faces. In Experiment 3, both smiling and angry faces were shown during each trial, and we found that social exclusion promotes attentional bias to smiling faces compared to angry faces. Therefore, the present study extends our understanding of the relationship between social exclusion and attention. Overall, it appears that after social exclusion, the desire for social reconnection trumps the desire to avoid social exclusion.
Colorectal preOperative Surgical Score (CrOSS) for mortality in major colorectal surgery
Authors: Kong Cherng Huei , Guest Glenn D. , Stupart Douglas A. , Faragher Ian G. , Chan Steven T. F. , Watters David A.
Published: March 2015

Background

Colorectal surgery carries a significant mortality risk, with reported rates of 1–6% for elective surgery and up to 22% in the emergency setting. Both clinicians and patients will benefit from being able to predict the likelihood of death before surgery. Recently, we have described and validated two risk stratification models for colorectal surgery, the Barwon Health 2012 and Association Française de Chirurgie models. However, these models are not suitable for assessment at patient's bedside. The purpose of this study is to develop a simplified preoperative model capable of predicting mortality following colorectal surgery.

Methods

The new model is termed Colorectal preOperative Surgical Score (CrOSS). The development and internal validation of CrOSS was performed using a prospectively maintained colorectal database. External validation was performed using retrospective data. Univariate and multivariate analyses were performed in model development. Calibration and discrimination were used for model validation.

Results

There were 474 and 389 consecutive colorectal surgeries at Geelong Hospital and Western Hospital. Overall mortality rates were 5.16% and 1.03%, respectively. Significant predictors for mortality were as follows: age ≥70, urgent operation, albumin ≤30 g/L and congestive heart failure (receiver operating characteristic (ROC) = 0.870, calibration P‐value = 0.937). The predicted risk of mortality was stratified according to the risk profile of 0.39–66.51%. When validated externally, CrOSS predicted mortality accurately (ROC = 0.847, calibration P‐value = 0.199).

Conclusions

A robust and simple preoperative model has been created to risk‐stratify patients for colorectal surgery. This was successfully validated at another tertiary hospital.
Forming a belief: The contribution of comprehension to the evaluation and persuasive impact of argumentative text
Authors: Diakidoy Irene‐Anna N. , Christodoulou Stelios A. , Floros Georgios , Iordanou Kalypso , Kargopoulos Philip V.
Published: March 2015

Background

Research has shown substantial belief change as a result of reading text and the pervasive influence of prior belief in the evaluation of short arguments. Both outcomes have been attributed to the depth to which the text or the argument has been processed. This study brings together critical thinking and text comprehension research by employing an extended argumentative text and varying the quality of its arguments.

Aim

The study examines the contribution of comprehension outcomes to the critical evaluation and persuasive impact of argumentative text.

Sample

One hundred and sixteen first‐year graduate and third‐ and fourth‐year undergraduate university students.

Method

Measures of initial topic‐related beliefs, perceived topic knowledge, and need for cognition were obtained. Students read one of two versions of a two‐sided, implicitly persuasive argumentative text (677 words) varying in argument quality. Post‐reading tasks included main claim recall, overall recall, inference generation, claim agreement, and text evaluation.

Results

The text was positively evaluated and highly persuasive regardless of argument quality, but half of the students either failed to identify the main claim promoted or confused it with individual arguments. Despite a modest but positive association between inference generation and text evaluation, no comprehension measure had a significant main or interactive effect. Need for cognition contributed to positive evaluations in the absence of prior topic knowledge regardless of argument quality.

Conclusions

The findings suggest a dissociation between the elaboration associated with deep comprehension and the elaboration associated with critical evaluation with implications for belief formation and the teaching of thinking.
Prognostic roles of absolute monocyte and absolute lymphocyte counts in patients with advanced‐stage follicular lymphoma in the rituximab era: an analysis from theFOLL05 trial of the Fondazione Italiana Linfomi
Authors: Marcheselli Luigi , Bari Alessia , Anastasia Antonella , Botto Barbara , Puccini Benedetta , Dondi Alessandra , Carella Angelo M. , Alvarez Isabel , Chiarenza Annalisa , Arcari Annalisa , Salvi Flavia , Federico Massimo
Published: March 2015

Recently, in an attempt to improve the discrimination power of the international prognostic index (IPI), patients with diffuse large B‐cell lymphoma were evaluated to determine the prognostic roles of peripheral blood absolute monocyte count (AMC) and absolute lymphocyte count (ALC). Here, we analysed data of 428 patients with follicular lymphoma (FL) enrolled in a prospective, randomized trial (FOLL05 study) conducted by Fondazione Italiana Linfomi, to assess the impact ofAMCandALCon progression‐free survival (PFS). All patients had been treated with one of three treatment combinations: (i) rituximab (R) plus cyclophosphamide, vincristine and prednisone; (ii) R plus cyclophosphamide, doxorubicin, vincristine and prednisone or (iii) R plus mitoxantrone and fludarabine. We showed that onlyAMCwas a powerful predictor ofPFS, and possibly overall survival, in patients withFLtreated with combination chemotherapy regimens that contained R. TheAMCcan be used alone as a novel, simple factor that can predict survival outcome in patients withFL, independent of the immunochemotherapy regimen. It may therefore be widely used by clinicians, due to its simplicity and broad applicability. Additionally, it can be combined with other factors that determine theIPIorFLIPI, to increase the discriminating ability of these indices.
A phase I/II study of sunitinib and intensive chemotherapy in patients over 60 years of age with acute myeloid leukaemia and activating FLT3 mutations
Authors: Fiedler Walter , Kayser Sabine , Kebenko Maxim , Janning Melanie , Krauter Jürgen , Schittenhelm Marcus , Götze Katharina , Weber Daniela , Göhring Gudrun , Teleanu Veronica , Thol Felicitas , Heuser Michael , Döhner Konstanze , Ganser Arnold , Döhner Hartmut , Schlenk Richard F.
Published: March 2015

Acute myeloid leukaemia (AML) with FLT3 mutation has a dismal prognosis in elderly patients. Treatment with a combination of FLT3 inhibitors and standard chemotherapy has not been extensively studied. Therefore, we instigated a phase I/II clinical trial of chemotherapy with cytosine arabinoside (Ara‐C)/daunorubicin induction (7+3) followed by three cycles of intermediate‐dose Ara‐C consolidation in 22 AML patients with activating FLT3 mutations. Sunitinib was added at predefined dose levels and as maintenance therapy for 2 years. At dose level 1, sunitinib 25 mg daily continuously from day 1 onwards resulted in two cases with dose‐limiting toxicity (DLT), prolonged haemotoxicity and hand‐foot syndrome. At dose level −1, sunitinib 25 mg was restricted to days 1–7 of each chemotherapy cycle. One DLT was observed in six evaluable patients. Six additional patients were treated in an extension phase. Thirteen of 22 patients (59%; 8/14 with FLT3–internal tandem duplication and 5/8 with FLT3‐tyrosine kinase domain) achieved a complete remission/complete remission with incomplete blood count recovery. For the 17 patients included at the lower dose level, median overall, relapse‐free and event‐free survival were 1·6, 1·0 and 0·4 years, respectively. Four out of five analysed patients with relapse during maintenance therapy lost their initial FLT3 mutation, suggesting outgrowth of FLT3 wild‐type subclones.
Four doses of unpegylated versus one dose of pegylated filgrastim as supportive therapy in R‐CHOP‐14 for elderly patients with diffuse large B‐cell lymphoma
Authors: Bozzoli Valentina , Tisi Maria C. , Maiolo Elena , Alma Eleonora , Bellesi Silvia , D'Alo’ Francesco , Voso Maria T. , Leone Giuseppe , Hohaus Stefan
Published: March 2015

The primary objective of this prospective, randomized study was to compare the efficacy of a reduced regimen of only four doses of unpegylated filgrastim from day +8 to +11 per cycle with a standard once per cycle administration of pegylated filgrastim to maintain dose‐intensity of R‐CHOP‐14 (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone given every 14 d) in previously untreated elderly patients with diffuse large B‐cell lymphoma (DLBCL). We included 51 patients (median age 66 years, range 60–76). Median dose intensity did not differ between the group of 24 patients receiving four doses of unpegylated filgrastim of each cycle (87·5%) and the group of 27 patients receiving pegylated filgrastim once per cycle on day 2 (89·4%) (P = 0·9). There was also no difference in the frequency of adverse events, such as episodes of neutropenic fever and unplanned hospitalizations. Patient characteristics that negatively influenced dose intensity were reduced performance status, advanced stage disease and poor‐risk International Prognostic Index, with Eastern Cooperative Oncology Group performance status ≥2 being the most significant factor. In conclusion, a limited support with 4 d of filgrastim appears to be equivalent to pegylated filgrastim administered once per cycle, and appears to be sufficient to maintain dose‐intensity of the R‐CHOP‐14 regimen in elderly patients with DLBCL without risk factors.
MYD88 L265P and CXCR4 mutations in lymphoplasmacytic lymphoma identify cases with high disease activity
Authors: Schmidt Janine , Federmann Birgit , Schindler Natalie , Steinhilber Julia , Bonzheim Irina , Fend Falko , Quintanilla‐Martinez Leticia
Published: March 2015

Recurrent mutations in MYD88 have been identified in >90% of lymphoplasmacytic lymphoma (LPL). Recently, WHIM (warts, hypogammaglobulinaemia, infections, myelokathexis) syndrome‐like mutations in CXCR4 have been described in 28% of LPL cases, and seem to impact clinical presentation and response to therapy. We investigated the presence of the MYD88 L265P mutation in 90 decalcified, formalin‐fixed, paraffin‐embedded (FFPE) bone marrow (BM) biopsies, including 51 cases of LPL, 14 cases of B‐cell chronic lymphocytic leukaemia (CLL), 13 cases of marginal zone lymphoma (MZL) and 12 normal controls. In addition, the C‐terminal domain of CXCR4 was sequenced in LPL cases. MYD88 L265P was found in 49/51 (96%) LPL cases and in 1/13 (7·6%) MZL (splenic type), whereas all CLL samples remained negative. The two MYD88 wild type LPL cases were associated with cold agglutinin disease. Mutations in CXCR4 were detected in 17/47 (36·2%) LPL cases, which showed a higher extent of BM infiltration and lower leucocyte counts (P = 0·02), haemoglobin (P = 0·05) and platelet counts (P = 0·01). In conclusion the detection of MYD88 L265P mutation in FFPE samples is reliable and useful for subtyping small B‐cell lymphomas in BM biopsies. In addition, the presence of CXCR4 mutations identifies a subgroup of LPL patients with higher disease activity.
Characterization of bone marrow mesenchymal stromal cells in aplastic anaemia
Authors: Hamzic Edita , Whiting Karen , Gordon Smith Edward , Pettengell Ruth
Published: March 2015

In aplastic anaemia (AA), haemopoietic activity is significantly reduced and generally attributed to failure of haemopoietic stem cells (HSC) within the bone marrow (BM). The regulation of haemopoiesis depends on the interaction between HSC and various cells of the BM microenvironment, including mesenchymal stromal cells (MSC). MSC involvement in the functional restriction of HSC in AA is largely unknown and therefore, the physical and functional properties of AA MSC were studied in vitro. MSC were characterized by their phenotype and ability to form adherent stromal layers. The functional properties of AA MSC were assessed through proliferative, clonogenic and cross‐over culture assays. Results indicate that although AA MSC presented typical morphology and distinctive mesenchymal markers, stromal formation was reduced, with 50% of BM samples failing to produce adherent layers. Furthermore, their proliferative and clonogenic capacity was markedly decreased (P = 0·03 and P = 0·04 respectively) and the ability to sustain haemopoiesis was significantly reduced, as assessed by total cell proliferation (P = 0·032 and P = 0·019 at Week 5 and 6, respectively) and clonogenic potential of HSC (P = 0·02 at Week 6). It was concluded that the biological characteristics of AA MSC are different from those of control MSC and their in vitro haemopoiesis‐supporting ability is significantly reduced.
Current approaches in the management of low risk Hodgkin lymphoma in children and adolescents
Authors: Giulino‐Roth Lisa , Keller Frank G. , Hodgson David C. , Kelly Kara M.
Published: March 2015

The outcome for children and adolescents with low risk Hodgkin lymphoma (HL) is excellent, with event‐free survival >85% and overall survival >95%. Historically, however, treatment has come at the cost of significant long‐term toxicity from chemotherapy, radiation or a combination of these. Recent treatment strategies have focused on maintaining high event‐free and overall survival while minimizing the use of therapy associated with late effects. The strategies used to achieve this vary greatly among paediatric cooperative groups and there is no one standard treatment for children with low risk HL. This review summaries recent clinical trials in paediatric low risk HL and addresses some of the important considerations when comparing trials, including differences in the definition of low risk HL, differences in outcome among histological subtypes and varying approaches to reduce or eliminate radiation therapy. Recommendations are provided for the treatment of children with low risk HL outside the setting of a clinical trial.
JAK1/2 inhibition impairs T cell function in vitro and in patients with myeloproliferative neoplasms
Authors: Parampalli Yajnanarayana Sowmya , Stübig Thomas , Cornez Isabelle , Alchalby Haefaa , Schönberg Kathrin , Rudolph Janna , Triviai Ioanna , Wolschke Christine , Heine Annkristin , Brossart Peter , Kröger Nicolaus , Wolf Dominik
Published: March 2015

Ruxolitinib (INCB018424) is the first JAK1/JAK2 inhibitor approved for treatment of myelofibrosis. JAK/STAT‐signalling is known to be involved in the regulation of CD4+ T cells, which critically orchestrate inflammatory responses. To better understand how ruxolitinib modulates CD4+ T cell responses, we undertook an in‐depth analysis of CD4+ T cell function upon ruxolitinib exposure. We observed a decrease in total CD3+ cells after 3 weeks of ruxolitinib treatment in patients with myeloproliferative neoplasms. Moreover, we found that the number of regulatory T cells (Tregs), pro‐inflammatory T‐helper cell types 1 (Th1) and Th17 were reduced, which were validated by in vitro studies. In line with our in vitro data, we found that inflammatory cytokines [tumour necrosis factor‐α (TNF), interleukin (IL)5, IL6, IL1B] were also downregulated in T cells from patients (all P < 0·05). Finally, we showed that ruxolitinib does not interfere with the T cell receptor signalling pathway, but impacts IL2‐dependent STAT5 activation. These data provide a rationale for testing JAK inhibitors in diseases triggered by hyperactive CD4+ T cells, such as autoimmune diseases. In addition, they also provide a potential explanation for the increased infection rates (i.e. viral reactivation and urinary tract infection) seen in ruxolitinib‐treated patients.
Clinical and laboratory characterization of 114 cases of Castleman disease patients from a single centre: paraneoplastic pemphigus is an unfavourable prognostic factor
Authors: Dong Yujun , Wang Mingyue , Nong Lin , Wang Lihong , Cen Xinan , Liu Wei , Zhu Sainan , Sun Yuhua , Liang Zeyin , Li Yuan , Ou Jinping , Qiu Zhixiang , Ren Hanyun
Published: March 2015

This study retrospectively collected the clinical and laboratory data of 114 patients with Castleman disease (CD) from a single medical centre. Clinical classification identified 62 patients (54·4%) with unicentric Castleman disease and 52 (45·6%) with multi‐centric Castleman disease. Pathological classification revealed 68 cases (59·6%) of hyaline vascular variant, 16 (14·1%) mixed cellular variant (Mix) and 30 (26·3%) plasmacytic variant. Clinical complications occurred in 69 CD patients, including 37 cases of paraneoplastic pemphigus (PNP) and 25 cases with renal complications. Haematological involvement, pleural effusion and/or ascites and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) were also found. Univariate analysis showed that presence of clinical complications and PNP were both risk factors relating to CD patient survival. Prognostic factors showing P < 0·15 in univariate analysis and those with clinical significance were subjected to multivariate analysis using a Cox regression model. PNP presence and age over 40 years both significantly adversely affected survival. Thus, only presence of PNP was identified as an independent unfavourable survival risk factor in both univariate and multivariate analyses. Overall, the present data provide a panoramic description of CD cases and emphasize that the presence of PNP is an adverse prognostic factor.
Ofatumumab retreatment and maintenance in fludarabine‐refractory chronic lymphocytic leukaemia patients
Authors: Österborg Anders , Wierda William G. , Mayer Jiří , Hess Georg , Hillmen Peter , Schetelig Johannes , Schuh Anna , Smolej Lukáš , Beck Christian , Dreyfus Brigitte , Hellman Andrzej , Kozlowski Piotr , Pfreundschuh Michael , Rizzi Rita , Spacek Martin , Phillips Jennifer L. , Gupta Ira V. , Williams Vanessa , Jewell Roxanne C. , Nebot Noelia , Lisby Steen , Dyer Martin J. S.
Published: March 2015

There are limited data on retreatment with monoclonal antibodies (mAb) in patients with chronic lymphocytic leukaemia (CLL). In a pivotal study, ofatumumab (human anti‐CD20 mAb) monotherapy demonstrated a 47% objective response rate (ORR) in fludarabine refractory CLL patients. From this study, a subset of 29 patients who had at least stable disease and then progressed were retreated with eight weekly ofatumumab infusions (induction treatment period), followed by monthly infusions for up to 2 years (maintenance treatment period). The ORR after 8 weeks of induction retreatment was 45% and 24% had continued disease control after maintenance at 52 weeks. Efficacy and safety of the retreated patients were compared with their initial results in the pivotal study. Response duration was 24·1 months vs. 6·8 months; time to next therapy was 14·8 months vs. 12·3 months; and progression‐free survival was 7·4 months vs. 7·9 months (medians). Upon retreatment, 72% had infusion reactions, mostly Grade 1–2. Three patients had fatal infections. In summary, ofatumumab retreatment and maintenance therapy was feasible in patients with heavily pretreated CLL and appeared to result in more durable disease control than initial ofatumumab treatment in this subset of patients who may have a more favourable disease profile.
Fatigue in immune thrombocytopenia
Authors: Hill Quentin A. , Newland Adrian C.
Published: March 2015

Fatigue is an important aspect of health‐related quality of life from the patient perspective and can have significant socio‐economic consequences. It is a common feature of chronic illnesses and a significant number of both adults and children with immune thrombocytopenia (ITP) suffer from fatigue. Reliable, validated fatigue scales have been developed for use in ITP. These will facilitate future investigation of its pathogenesis and the effectiveness of intervention. Acute inflammation acts on neural and endocrine systems resulting in ‘sickness behaviour’, an adaptive response to infection and injury. Inflammation is also thought to cause fatigue in chronic disease and immune dysregulation in ITP appears to have a number of pro‐inflammatory components. Clinicians should consider fatigue when assessing the burden of disease. Although effective ITP‐directed therapy can improve fatigue, a number of fatigue‐directed strategies may also need to be considered.
Secondary acute lymphoblastic leukaemia is constitutional and probably not related to prior therapy
Authors: Ganzel Chezi , Devlin Sean , Douer Dan , Rowe Jacob M. , Stein Eytan M. , Tallman Martin S.
Published: March 2015

Very little is known about secondary acute lymphoblastic leukaemia (s‐ALL). This retrospective analysis studied a cohort of s‐ALL patients treated at a single centre between 1994 and 2013, while comparing therapy‐associated ALL (t‐ALL) and antecedent malignancy ALL (am‐ALL) patients. Thirty‐two patients with s‐ALL were identified. The overall incidence was 9·4% among ALL adults while T‐cell s‐ALL was rare (12% of s‐ALLs). The median time interval between two malignant diagnoses was 5·3 years (range: 0·1–28). In contrast to previous reports, most of the s‐ALLs were CD10 +  and without KMT2A (MLL) abnormalities. The overall survival (OS) rates of the entire cohort at 12 and 24 months from ALL diagnosis was 49% and 25%, respectively. Most patients (n = 23, 72%) received prior chemo‐/radio‐therapy for their first malignancy (t‐ALL) and only 9 (28%) did not (am‐ALL). No significant difference was found in the incidence of B‐/T‐ lineage ALL, extramedullary disease, blood count, and the rate of Philadelphia‐positive ALL, nor in the rates of complete remission (P = 0·55) and OS (P = 0·97). This similarity, together with high incidence of family malignancy in both groups, raise the possibility that s‐ALL patients may have an inherent predisposition to malignancies and a history of previous therapy may be of lesser importance in the pathogenesis of s‐ALL.
Proteomic profiling of naïve multiple myeloma patient plasma cells identifies pathways associated with favourable response to bortezomib‐based treatment regimens
Authors: Dytfeld Dominik , Rosebeck Shaun , Kandarpa Malathi , Mayampurath Anoop , Mellacheruvu Dattatreya , Alonge Mattina M. , Ngoka Lambert , Jasielec Jagoda , Richardson Paul G. , Volchenboum Samuel , Nesvizhskii Alexey I. , Sreekumar Arun , Jakubowiak Andrzej J.
Published: March 2015

Toward our goal of personalized medicine, we comprehensively profiled pre‐treatment malignant plasma cells from multiple myeloma patients and prospectively identified pathways predictive of favourable response to bortezomib‐based treatment regimens. We utilized two complementary quantitative proteomics platforms to identify differentially‐regulated proteins indicative of at least a very good partial response (VGPR) or complete response/near complete response (CR/nCR) to two treatment regimens containing either bortezomib, liposomal doxorubicin and dexamethasone (VDD), or lenalidomide, bortezomib and dexamethasone (RVD). Our results suggest enrichment of ‘universal response’ pathways that are common to both treatment regimens and are probable predictors of favourable response to bortezomib, including a subset of endoplasmic reticulum stress pathways. The data also implicate pathways unique to each regimen that may predict sensitivity to DNA‐damaging agents, such as mitochondrial dysfunction, and immunomodulatory drugs, which was associated with acute phase response signalling. Overall, we identified patterns of tumour characteristics that may predict response to bortezomib‐based regimens and their components. These results provide a rationale for further evaluation of the protein profiles identified herein for targeted selection of anti‐myeloma therapy to increase the likelihood of improved treatment outcome of patients with newly‐diagnosed myeloma.
Immune checkpoint inhibition in lymphoid disease
Authors: Eyre Toby A. , Collins Graham P.
Published: March 2015

It has long been understood that the immune system has intrinsic anti‐tumour activity in humans, and that a key mechanism of tumour progression is the ability of a tumour to escape this immune surveillance. A number of attempts have been made to harness this anti‐tumour immunity in both solid tumour oncology and haematological malignancies with variable success. Examples include the use of allogeneic stem cell transplantation and donor lymphocyte infusion in haematological cancer and vaccine studies in solid tumours. Enhanced signalling of the Programmed cell death‐1 (PDCD1, PD‐1)/cytotoxic T‐lymphocyte‐associated protein 4 (CTLA4) ‘immune checkpoint’ pathway has emerged recently as a critical mechanism by which tumours can escape the natural anti‐tumour immune response. As such, novel therapies have been developed to help enhance this natural immunity by switching off the PDCD1/CTLA4 immune checkpoint pathway. The following review will discuss the pathobiology of these pathways and the exciting new data now available in lymphoid malignancies.
Peatland initiation and carbon dynamics in northeast China: links to Holocene climate variability
Authors: Xing Wei , Bao Kunshan , Guo Wenyong , Lu Xianguo , Wang Guoping
Published: March 2015

Throughout northeast China, the widely distributed peatlands have formed a large carbon (C) pool. However, the relationship between peatland initiation and climate controls is still poorly documented and understood. Understanding the responses of these C‐rich ecosystems to past climate change will provide useful insights into projecting the fate of peatland C in the future. In this study, we present a detailed historical reconstruction of peatland development in northeast China based on 312 basal peat dates, and examine the relationship between Holocene peatland dynamics and climate sensitivity. Our results indicate that peatland initiation started in the early Holocene, and that the majority of peatlands were initiated by and developed during the late Holocene. After the most intensive initiation period of 4.2–0.8 ka, the rate of peatland development slowed, which was concomitant with decreasing insolation and monsoon intensity. The widespread peatland initiation in the late Holocene might have been caused by the cool and moist climate patterns. The optimum timing of the peatland development was not uniform across northeast China, and these spatio‐temporal differences indicate the influences of regional climate and terrain on peatland initiation. Peat‐core data show variations in the long‐term apparent rate of C accumulation (LORCA) during the Holocene, with an average rate of 37.2 g C m−2 a−1. The peak LORCA occurred during 10.5–9.0 ka, probably in response to higher temperatures and stronger East Asia summer monsoon intensities. Both temperature and humidity are important factors influencing the peatland initiation and C dynamics in this region.
‘Conditioning the heart’ – lessons we have learned from the past and future perspectives for new and old conditioning ‘drugs’
Authors: Weber Nina C
Published: March 2015

Linked Articles

This article is part of a themed section on Conditioning the Heart – Pathways to Translation. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐8
Elevated whole blood viscosity is associated with insulin resistance and non‐alcoholic fatty liver
Authors: Zhao Hong‐yan , Li Jing , Xu Min , Wang Tian‐ge , Sun Wan‐wan , Chen Ying , Bi Yu‐fang , Wang Wei‐qing , Ning Guang
Published: March 2015

Background

Accumulating evidences demonstrate that abnormalities in whole blood viscosity (WBV) have been implicated in insulin resistance which may lead to non‐alcoholic fatty liver disease (NAFLD). However, epidemiological studies exploring the association between WBV and NAFLD were not available.

Objective

Our objective was to evaluate the association between WBV levels and risk of prevalent NAFLD.

Design

This was a cross‐sectional population‐based study performed in Shanghai, China.

Patients

A total of 8673 participants aged 40 years or older were included.

Measurements

WBV was calculated from haematocrit and plasma protein concentration, at a shear rate of 208−1 s, by a validated equation. NAFLD was diagnosed by hepatic ultrasound after the exclusion of alcohol abuse and other liver diseases. Insulin resistance (IR) was assessed by homeostasis model assessment (HOMA‐IR).

Results

The overall prevalence of NAFLD was 30·2% in this population. With the increase of WBV level, participants have larger waist circumference (WC), more severe insulin resistance and the prevalence of NAFLD increased significantly with elevated WBV quartiles. Compared with those in the lowest quartiles, adults in the highest quartile of WBV levels have higher prevalence of NAFLD (adjusted odds ratio 1·77, 95% confidence interval [CI] 1·48–2·13) and IR (2·72, 95% CI 2·26–3·27).

Conclusions

Elevated WBV is associated with prevalence of NAFLD and IR in middle‐aged and elderly Chinese population.
Benefits and risks of immediately sequential bilateral cataract surgery: a literature review
Authors: Lansingh Van C , Eckert Kristen A , Strauss Glenn
Published: March 2015

Immediately sequential bilateral cataract surgery (ISBCS) is a highly contended issue in ophthalmology, mainly due to the risk of bilateral endophthalmitis and financial penalties that many ophthalmologists face when performing simultaneous cataract surgeries. The purpose of this review is to understand the current status of the knowledge of ISBCS, mainly its benefits and risks and how they compare with the standard of care, delayed sequential bilateral cataract surgery. Evidence, although limited, increasingly supports ISBCS for providing faster rehabilitation, improved visual outcomes, and cost and time savings. Evidence does not support the fear of bilateral endophthalmitis resulting from the simultaneous procedure. However, stronger and greater evidence is needed before ISBCSs can be considered the standard of care. Where ISBCS can potentially create the most beneficial impact is in public eye health programmes in developing countries, but this has not yet been explored.
Low penetrance of paraganglioma and pheochromocytoma in an extended kindred with a germline SDHB exon 3 deletion
Authors: Rijken J.A. , Niemeijer N.D. , Corssmit E.P.M. , Jonker M.A. , Leemans C.R. , Menko F.H. , Hensen E.F.
Published: March 2015

In the Netherlands, the majority of hereditary paragangliomas (PGL) is caused by SDHD, SDHB and SDHAF2 mutations. Founder mutations in SDHD are particularly prevalent, but several SDHB founder mutations have also been described. Here, we describe an extended PGL family with a Dutch founder mutation in SDHB, c.201‐4429_287‐933del. The proband presented with apparently sporadic head and neck paraganglioma at advanced age. Subsequently, evaluation of the family identified several unaffected mutation carriers, asymptomatic and symptomatic PGL patients, and patients presenting with early‐onset malignant pheochromocytoma. The calculated penetrance of the SDHB mutation in this kindred is lower than the risk suggested for SDHB mutations in the literature. This may represent a characteristic of this particular SDHB mutation, but may also be a reflection of the inclusion of relatively large numbers of asymptomatic mutation carriers in this family and adequate statistical correction for ascertainment bias. The low penetrance of SDHB mutations may obscure the hereditary nature of SDHB‐linked disease and is important in the counseling of SDHB‐linked patients. Risk estimates should preferably be based on the specific mutation involved.
Comparative Evaluation of Changes in Brain Activity and Cognitive Function of Edentulous Patients, with Dentures and Two‐Implant Supported Mandibular Overdenture‐Pilot Study
Authors: Banu R Fathima , Veeravalli Padmanabhan T. , Kumar V Anand
Published: March 2015

Background

The relationship between brain and prosthesis was previously assessed either by improving denture function or in fixed implant retained, wherein brain function was assessed only after crown placement.

Purpose

To prospectively analyze the changes in brain activity and cognitive function of completely edentulous patients in edentulous state, with dentures and two‐implant supported mandibular overdenture before and after loading, along with the effect of mastication in the change – a pilot study.

Materials and Method

Ten completely edentulous (CE) non‐denture wearers were selected. The mandibular prosthesis was loaded with two 3.3 mm × 13 mm myriad snap fit implants. To assess the brain activity and cognitive function, Electroencephalogram (Neurofax EEG 1000 Ver 05–90, Nihon Kohden corporation, Tokyo, Japan) and Mini‐Mental State Examination (MMSE) questionnaire, respectively, were taken during the process of rehabilitation. EEG assessment was analyzed using Matlab 2011A 7.9 signal processing tool box. The results were statistically analyzed with SPSS 17.0 version using Wilcoxon signed rank and Friedman test

Results

Amplitude, power of alpha waves and cognitive scores increased gradually with highest mean rank for implant supported overdenture (IOD). The bivariate analysis between two groups showed there was significant difference between all the groups (p < 0.05) except for groups CE‐I (completely edentulous – implant placement) and CD‐ I (complete denture insertion – implant placement) in amplitude of alpha waves while in group CD‐I with respect to power of alpha waves. MMSE revealed the mean of cognitive scores in Complete Edentulous was 17.40, Complete Denture was 18.30 and finally with Implant Overdenture was 23.80.

Conclusion

The present study has enlightened the significance of two implant supported mandibular overdenture in improving the mental state of an individual and that the enhancement was due to functional improvement with prosthesis when loaded with implants and not due to mere existence of implant without any function.