bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergistic effect of phosphodiesterase 4 inhibitor and serum on migration of endotoxin-stimulated macrophages
Authors: Yang Jing-Xing , Hsiung Te-Chih , Weng Fu-Chun , Ding Shiau-Li , Wu Chin-Pyng , Conti Marco , Chuang Tsung-Hsien , Catherine Jin S-L
Published: November 2018

Macrophage migration is an essential step in host defense against infection and wound healing. Elevation of cAMP by inhibiting phosphodiesterase 4 (PDE4), enzymes that specifically degrade cAMP, is known to suppress various inflammatory responses in activated macrophages, but the role of PDE4 in macrophage migration is poorly understood. Here we show that the migration of Raw 264.7 macrophages stimulated with LPS was markedly and dose-dependently induced by the PDE4 inhibitor rolipram as assessed by scratch wound healing assay. Additionally, this response required the involvement of serum in the culture medium as serum starvation abrogated the effect. Further analysis revealed that rolipram and serum exhibited synergistic effect on the migration, and the influence of serum was independent of PDE4 mRNA expression in LPS-stimulated macrophages. Moreover, the enhanced migration by rolipram was mediated by activating cAMP/exchange proteins directly activated by cAMP (Epac) signaling, presumably via interaction with LPS/TLR4 signaling with the participation of unknown serum components. These results suggest that PDE4 inhibitors, together with serum components, may serve as positive regulators of macrophage recruitment for more efficient pathogen clearance and wound repair.
Sensorial frailty: age-related hearing loss and the risk of cognitive impairment and dementia in later life
Authors: Panza Francesco , Lozupone Madia , Sardone Rodolfo , Battista Petronilla , Piccininni Marco , Dibello Vittorio , La Montagna Maddalena , Stallone Roberta , Venezia Pietro , Liguori Angelo , Giannelli Gianluigi , Bellomo Antonello , Greco Antonio , Daniele Antonio , Seripa Davide , Quaranta Nicola , Logroscino Giancarlo
Published: November 2018

The peripheral hearing alterations and central auditory processing disorder (CAPD) associated with age-related hearing loss (ARHL), may impact cognitive disorders in older age. In older age, ARHL is also a significant marker for frailty, another age-related multidimensional clinical condition with a nonspecific state of vulnerability, reduced multisystem physiological reserve, and decreased resistance to different stressors (i.e. sensorial impairments, psychosocial stress, diseases, injuries). The multidimensional nature of frailty required an approach based on different pathogeneses because this clinical condition may include sensorial, physical, social, nutritional, cognitive, and psychological phenotypes. In the present narrative review, the cumulative epidemiological evidence coming from several longitudinal population-based studies, suggested convincing links between peripheral ARHL and incident cognitive decline and dementia. Moreover, a few longitudinal case-control and population-based studies also suggested that age-related CAPD in ARHL, may be central in determining an increased risk of incident cognitive decline, dementia, and Alzheimer’s disease (AD). Cumulative meta-analytic evidence confirmed cross-sectional and longitudinal association of both peripheral ARHL and age-related CAPD with different domains of cognitive functions, mild cognitive impairment, and dementia, while the association with dementia subtypes such as AD and vascular dementia remained unclear. However, ARHL may represent a modifiable condition and a possible target for secondary prevention of cognitive impairment in older age, social isolation, late-life depression, and frailty. Further research is required to determine whether broader hearing rehabilitative interventions including coordinated counseling and environmental accommodations could delay or halt cognitive and global decline in the oldest old with both ARHL and dementia.
Use of immunohistochemical analysis of CK5/6, CK14, and CK34betaE12 in the differential diagnosis of solid papillary carcinoma in situ from intraductal papilloma with usual ductal hyperplasia of the breast
Authors: Maeda Ichiro , Tajima Shinya , Kanemaki Yoshihide , Tsugawa Koichiro , Takagi Masayuki
Published: November 2018

Objectives:

The aim of this study was to use immunohistochemistry to differentiate solid papillary carcinoma in situ from intraductal papilloma with usual ductal hyperplasia (IPUDH). Three types of high-molecular-weight cytokeratins (CKs) – CK5/6, CK14, and CK34betaE12 – were targeted.

Methods:

We studied 17 patients with solid papillary carcinoma in situ and 18 patients with IPUDH diagnosed by at least two pathologists. Immunohistochemical analyses used antibodies to CK5/6, CK14, and CK34betaE12 to make the differential diagnosis of solid papillary carcinoma in situ versus IPUDH. Immunohistochemical staining was scored as 0–5 using Allred score.

Results:

Immunohistochemistry with CK5/6 and CK14 antibodies produced scores of 0–3 in all patients with solid papillary carcinoma in situ and 2–5 in all patients with IPUDH. Immunohistochemical staining with CK34betaE12 antibody produced scores of 1–3 in all patients with solid papillary carcinoma and 3–5 in all patients with IPUDH. In tissues from patients with IPUDH, significantly more cells were stained with CK34betaE12 than CK5/6 ( p < 0.05) or CK14 ( p < 0.05).

Conclusion:

The immunoreactivity of CK5/6, CK14, and CK34betaE12 antibodies was useful to differentiate solid papillary carcinoma in situ from IPUDH. CK34betaE12 is especially useful for distinguishing solid papillary carcinoma from IPUDH.
Coping and adjustment in caregivers: A systematic review
Authors: Hawken Tamsyn , Turner-Cobb Julie , Barnett Julie
Published: November 2018

This systematic review assessed coping and adjustment in caregivers of all ages to provide a synthesis of existing literature in the context of methodological approaches and underlying theory. Four databases were searched. Reference lists, citations and experts were consulted. In total, 27 studies (13 quantitative and 14 qualitative) were included. Coping factors associated with adjustment (problem- versus emotion-focussed coping and cognitive strategies) and psychosocial factors associated with physiological adjustment (trait anxiety, coping style and social support) were identified. Results raised methodological issues. Future research requires physiological adjustment measures and longitudinal assessment of the long-term impact of childhood caregiving. Findings inform future caregiver research and interventions.
Granulomatous rhinitis secondary to feline leishmaniosis: report of an unusual presentation and therapeutic complications
Authors: Leal Rodolfo Oliveira , Pereira Hugo , Cartaxeiro Clara , Delgado Esmeralda , Peleteiro Maria da Conceição , Pereira da Fonseca Isabel
Published: November 2018

Case summary

A 12-year-old male neutered domestic shorthair cat underwent rhinoscopy due to inspiratory dyspnoea and stertor. Rhinoscopy showed signs of chronic rhinitis and a multinodular nasopharyngeal mucosa. A marked infiltrate of macrophages that contained intracellular parasitic forms morphologically compatible with Leishmania amastigotes were observed on histopathological examination of nasal and nasopharyngeal biopsies. PCR from nasal tissue was positive for Leishmania infantum DNA, confirming the diagnosis of granulomatous rhinitis secondary to this parasite. Two eyelid nodules were identified 2 weeks later. Fine-needle aspiration revealed Leishmania amastigotes within macrophages and in the background. Allopurinol therapy was started, but 5 days later the cat developed dermatological signs compatible with a cutaneous adverse drug reaction. The drug was discontinued and meglumine antimoniate prescribed. Twenty-five days later, the cat presented with acute kidney injury and meglumine antimoniate was discontinued. Despite clinical improvement after fluid therapy, mild azotaemia persisted. The cat was subsequently treated with nucleotides and active hexose correlated compounds (N-AHCC). Four months later upper respiratory signs were exacerbated. A relapse of granulomatous rhinitis was suspected and miltefosine therapy started. Chronic kidney disease (CKD) worsened during miltefosine treatment, having improved under fluid therapy. Since then, the cat has been treated with N-AHCC and renal diet and at the time of writing shows stable CKD with no recurrence of respiratory signs.

Relevance and novel information

This case describes Leishmania infantum as a cause of granulomatous rhinitis in a cat without cutaneous lesions, reporting the alternative use of N-AHCC and miltefosine when allopurinol seemed to have induced a cutaneous rash and there was acute kidney injury (AKI) after meglumine antimoniate therapy.
Book Review: Chinnaiah Jangam, Dalits and the Making of Modern India, Sambaiah Gundimeda, Dalit Politics in Contemporary India and Hugo Gorringe, Panthers in Parliament Dalits, Caste and Political Power in South India
Authors: Pai Sudha
Published: November 2018

Chinnaiah Jangam, Dalits and the Making of Modern India. New Delhi: Oxford University Press. 2017. 264 pages. ₹630.

Sambaiah Gundimeda, Dalit Politics in Contemporary India. New Delhi: Routledge. 2016. 294 pages. ₹1,595.

Hugo Gorringe, Panthers in Parliament Dalits, Caste and Political Power in South India. New Delhi: Oxford University Press. 2017. 424 pages. ₹995.
Book Review: Manisha Priyam, Contested Politics of Educational Reform in India
Authors: Menon Radhika
Published: November 2018

Manisha Priyam, Contested Politics of Educational Reform in India. New Delhi: Oxford University Press. 2015. 320 pages. ₹895.
An Integrated AFS-Based SWOT Analysis Approach for Evaluation of Strategies Under MCDM Environment
Authors: Singh Sunil Pratap , Singh Preetvanti
Published: November 2018

This article outlines the development of a hybrid methodology aimed to help the policymakers in strategic planning. The proposed methodology integrates the axiomatic fuzzy set (AFS) theory, analytic hierarchy process (AHP), and the concept of simple additive weighting (SAW) to evaluate the strategies by strengths, weaknesses, opportunities, and threats (SWOT) analysis. The combination of AHP with SWOT yields analytically determined weights of the factors included in SWOT analysis. The SAW technique provides a flexible technique to obtain the final ranking of strategies in multi-criteria decision situations. In SAW, the strategies are described using the AFS-based AHP calculation framework for normalization and consistent ratings over the SWOT factors. The AFS theory is incorporated in the model to overcome the uncertainty and ambiguity in human decision-making processes. The proposed integrated methodology copes with the inconsistency caused by different types of fuzzy numbers and normalization methods required in solving multi-criteria decision-making (MCDM) problems. A real-world application is conducted to illustrate the utilization of the model to evaluate SWOT analysis and strategies for tourism development.
Voudourisite, Cd(SO4)·H2O, and lazaridisite, Cd3(SO4)3·8H2O, two new minerals from the Lavrion Mining District, Greece
Authors: Rieck Branko , Lengauer Christian L. , Giester Gerald
Published: November 2018

Voudourisite, Cd(SO4)·H2O, and lazaridisite, Cd3(SO4)3·8H2O, are two new minerals from the Esperanza Mine, Kaminiza Area, Lavrion Mining District, Greece. This small ancient mine is also the type locality of niedermayrite and katerinopoulosite. Further associated minerals are sphalerite, galena, edwardsite, chalcanthite, gypsum and greenockite. Both secondary minerals form tiny clusters or crusts and are among the latest to form in this paragenetic sequence. They are colourless or white, transparent to translucent, with a white streak and vitreous lustre. No fluorescence is observed. The minerals exhibit conchoidal fracture, no cleavage or preferred parting. The Mohs hardness is ~3 and both have brittle tenacity. Voudourisite is biaxial (–) with refractive indices at 589(1) nm of α = 1.580(2), β = 1.624(2), γ = 1.640(2), 2Vmeas.= 70(5)°, 2Vcalc.= 61° and β ~ || [010]. Lazaridisite is biaxial neutral with refractive indices at 589(1) nm of α = 1.552(2), β = 1.561(2), γ = 1.570(2), 2Vmeas.= 90(5)° and 2Vcalc.= 90°. The chemical compositions of voudourisite and lazaridisite are close to ideal with only minor amounts of copper detectable. The atomic arrangement in voudourisite (space groupP21/cwitha= 7.633(2),b= 7.458(2),c= 8.151(2) Å, β = 122.35(1)° andV= 392.0(2) Å3) is related to that of kieserite while lazaridisite (space groupC2/cwitha= 14.813(3),b= 11.902(2),c= 9.466(2) Å, β = 97.38(1)° andV= 1655.2(6) Å3) is a distinct structure-type. Calculated densities are 3.838 and 3.088 g/cm3, respectively.

The strongest lines in the powder X-ray pattern [din Å (I) (hkl)] are: 4.890 (66) (110); 3.741 (25) (020); 3.578 (100) (11$\bar 2$); 3.230 (43) (200); 2.525 (33) (022); 2.395 (29) (112) for voudourisite and 6.860 (100) (200); 6.317 (72) (111); 5.965 (84) (020); 4.512 (58) (310); 3.727 (78) (202); 3.608(82)(13$\bar 1$); 3.109 (83) (40$\bar 2$); 3.020 (50) (33$\bar 1$) for lazaridisite, respectively.
Increased Ripk1-mediated bone marrow necroptosis leads to myelodysplasia and bone marrow failure in mice
Authors: Wagner Patrice N. , Shi Qiong , Salisbury-Ruf Christi T. , Zou Jing , Savona Michael R. , Fedoriw Yuri , Zinkel Sandra S.
Published: November 2018

Hematopoiesis is a dynamic system that requires balanced cell division, differentiation, and death. The 2 major modes of programmed cell death, apoptosis and necroptosis, share molecular machinery but diverge in outcome with important implications for the microenvironment; apoptotic cells are removed in an immune silent process, whereas necroptotic cells leak cellular contents that incite inflammation. Given the importance of cytokine-directed cues for hematopoietic cell survival and differentiation, the impact on hematopoietic homeostasis of biasing cell death fate to necroptosis is substantial and poorly understood. Here, we present a mouse model with increased bone marrow necroptosis. Deletion of the proapoptotic Bcl-2 family members Bax and Bak inhibits bone marrow apoptosis. Further deletion of the BH3-only member Bid (to generate VavCreBaxBakBid triple-knockout [TKO] mice) leads to unrestrained bone marrow necroptosis driven by increased Rip1 kinase (Ripk1). TKO mice display loss of progenitor cells, leading to increased cytokine production and increased stem cell proliferation and exhaustion and culminating in bone marrow failure. Genetically restoring Ripk1 to wild-type levels restores peripheral red cell counts as well as normal cytokine production. TKO bone marrow is hypercellular with abnormal differentiation, resembling the human disorder myelodysplastic syndrome (MDS), and we demonstrate increased necroptosis in MDS bone marrow. Finally, we show that Bid impacts necroptotic signaling through modulation of caspase-8–mediated Ripk1 degradation. Thus, we demonstrate that dysregulated necroptosis in hematopoiesis promotes bone marrow progenitor cell death that incites inflammation, impairs hematopoietic stem cells, and recapitulates the salient features of the bone marrow failure disorder MDS.
Mayo alliance prognostic system for mastocytosis: clinical and hybrid clinical-molecular models
Authors: Pardanani Animesh , Shah Sahrish , Mannelli Francesco , Elala Yoseph C. , Guglielmelli Paola , Lasho Terra L. , Patnaik Mrinal M. , Gangat Naseema , Ketterling Rhett P. , Reichard Kaaren K. , Hanson Curtis A. , Vannucchi Alessandro M. , Tefferi Ayalew
Published: November 2018

Systemic mastocytosis (SM) is a clinically heterogeneous disease with prognosis chiefly assigned based on World Health Organization (WHO) morphologic subclassification. We assessed the feasibility of developing contemporary risk models for SM based on clinical and integrated clinical-genetics information. Diagnosis of SM was per WHO criteria, and karyotype and next-generation sequencing data were available in a subset of the total 580 patients (median age, 55 years; range, 18-88 years) seen at the Mayo Clinic between 1968 and 2015. Morphologic subcategories were indolent/smoldering in 291 (50%) and “advanced” in 289 (50%): SM with an associated hematological neoplasm in 199, aggressive SM in 85, and mast cell leukemia in 5. Multivariable analysis of clinical variables identified age >60 years, advanced SM, thrombocytopenia <150 × 109/L, anemia below sex-adjusted normal, and increased alkaline phosphatase (ALP) as independent risk factors for survival; respective hazard ratios (HRs) 95% confidence intervals (95% CIs) were 2.5 (1.9-3.4), 2.7 (1.8-4.0), 2.5 (1.9-3.4), 2.2 (1.6-3.1), and 2.1 (1.5-3.0). In addition, ASXL1 (HR, 4.5; 95% CI, 2.6-7.6), RUNX1 (HR, 4.3; 95% CI, 1.3-10.8), and NRAS (HR, 5.0, 95% CI, 1.5-13.2) mutations were independently associated with inferior survival. Combined clinical, cytogenetic, and molecular risk factor analysis confirmed the independent prognostic contribution of adverse mutations (2.6, 1.6-4.4), advanced SM (4.0, 1.8-10.0), thrombocytopenia (2.8, 1.7-4.5), increased ALP (2.1, 1.2-4.0), and age >60 years (2.2, 1.3-3.6). These data were subsequently used to develop clinical and hybrid clinical-molecular risk models. The current study advances 2 complementary risk models for SM and highlights the independent prognostic contribution of mutations.
Increasing access to psychological treatments for adults by improving uptake and equity: rationale and lessons from the UK
Authors: Brown June S. L.
Published: November 2018

Objectives

Access to psychological treatments has been defined by Gulliford as comprising supply, effectiveness, equity and uptake. In the UK, a recent national programme “Improving Access to Psychological Treatments” has significantly increased supply and assessed effectiveness, but paid less attention to uptake and equity. The model developed by Gask et al. delineating processes relevant to improving access for ‘hard-to-engage’ groups in the UK, including black and minority groups seems relevant. This paper presents studies of a large-scale ‘community workshop’ intervention model developed by Brown to improve access for adults in the UK, designed to improve uptake and equity. We describe two ‘community workshop’ interventions for common mental health problems to which people have been able to self-refer and where uptake and equity have been high. Key components of this model are a ‘group-sensitive engagement’ ethos which includes self-referral, non-diagnostic titles of the intervention, a non-mental health setting, face-to-face presentation as well as a brief intervention and an acceptable format.

Conclusion

The model of community workshops with its ‘group-sensitive engagement’ ethos to which adults can self-refer may be very relevant in providing access for people with mental health needs in national and international settings.

Trial registration Classic ISRCTN26634837
What Is the Effectiveness of Patient Decision Aids for Cancer-Related Decisions? A Systematic Review Subanalysis
Authors: McAlpine Kristen , Lewis Krystina B. , Trevena Lyndal J. , Stacey Dawn
Published: November 2018

Purpose

To determine the effectiveness of patient decision aids when used with patients who face cancer-related decisions.

Patients and Methods

Two reviewers independently screened the 105 trials in the original 2017 Cochrane review to identify eligible trials of patient decision aids across the cancer continuum. Primary outcomes were attributes of the choice and decision-making process. Secondary outcomes were patient behavior and health system effects. A meta-analysis was conducted for similar outcome measures.

Results

Forty-six trials evaluated patient decision aids for cancer care, including 27 on screening decisions (59%), 12 on treatments (26%), four on genetic testing (9%), and three on prevention (6%). Common decisions were aboutprostate cancer screening (30%), colorectal cancer screening (22%), breast cancer treatment (13%), and prostate cancer treatment (9%). Compared with the control groups (usual care or alternative interventions), the patient decision aid group improved the match between the chosen option and the features that mattered most to the patient as demonstrated by improved knowledge (weighted mean difference, 12.88 of 100; 95% CI, 9.87 to 15.89; 24 trials), accurate risk perception (risk ratio [RR], 1.77; 95% CI, 1.22 to 2.56; six trials), and value-choice agreement (RR, 2.76; 95% CI, 1.57 to 4.84; nine trials). Compared with controls, the patient decision aid group improved the decision-making process with decreased decisional conflict (weighted mean difference, −9.56 of 100; 95% CI, −13.90 to −5.23; 12 trials), reduced clinician-controlled decision making (RR, 0.57; 95% CI, 0.41 to 0.79; eight trials), and fewer patients being indecisive (RR, 0.59; 95% CI, 0.45 to 0.78; nine trials).

Conclusion

Patient decision aids improve the attributes of the choice made and decision-making process for patients who face cancer-related decisions.
Prospects and Challenges for Clinical Decision Support in the Era of Big Data
Authors: El Naqa Issam , Kosorok Michael R. , Jin Judy , Mierzwa Michelle , Ten Haken Randall K.
Published: November 2018

Recently, there has been burgeoning interest in developing more effective and robust clinical decision support systems (CDSSs) for oncology. This has been primarily driven by the demands for more personalized and precise medical practice in oncology in the era of so-called big data (BD), an era that promises to harness the power of large-scale data flow to revolutionize cancer treatment. This interest in BD analytics has created new opportunities as well as new unmet challenges. These include: routine aggregation and standardization of clinical data, patient privacy, transformation of current analytical approaches to handle such noisy and heterogeneous data, and expanded use of advanced statistical learning methods on the basis of confluence of modern statistical methods and machine learning algorithms. In this review, we present the current status of CDSSs in oncology, the prospects and current challenges of BD analytics, and the promising role of integrated modern statistics and machine learning algorithms in predicting complex clinical end points, individualizing treatment rules, and optimizing dynamic personalized treatment regimens. We discuss issues pertaining to these topics and present application examples from an aggregate of experiences. We also discuss the role of human factors in improving the use and acceptance of such enhanced CDSSs and how to mitigate possible sources of human error to achieve optimal performance and wider acceptance.
Treatment Options in Oncology
Authors: Panje Cédric M. , Glatzer Markus , Sirén Charlotta , Plasswilm Ludwig , Putora Paul M.
Published: November 2018

Multiple treatment strategies exist for many oncologic problems. In this review, we provide a summary of various reasons for the existence of multiple treatment options in oncology, including factors that concern the treating physician (eg, treatment preferences), environmental factors (eg, financial, regulatory, and scientific aspects), and individual patient-specific factors (eg, medical condition, preferences). We demonstrate the vital role of available treatment options and their origins for clinical decision making and patient communication. These aspects are particularly helpful in the process of shared decision making, which is increasingly favored in situations where there are multiple medically reasonable options.
From Drosophila segmentation to human cancer therapy
Authors: Ingham Philip W.
Published: November 2018

First described in Drosophila, Hedgehog signalling is a key regulator of embryonic development and tissue homeostasis and its dysfunction underlies a variety of human congenital anomalies and diseases. Although now recognised as a major target for cancer therapy as well as a mediator of directed stem cell differentiation, the unveiling of the function and mechanisms of Hedgehog signalling was driven largely by an interest in basic developmental biology rather than clinical need. Here, I describe how curiosity about embryonic patterning led to the identification of the family of Hedgehog signalling proteins and the pathway that transduces their activity, and ultimately to the development of drugs that block this pathway.
The regulation of the homeostasis and regeneration of peripheral nerve is distinct from the CNS and independent of a stem cell population
Authors: Stierli Salome , Napoli Ilaria , White Ian J. , Cattin Anne-Laure , Monteza Cabrejos Anthony , Garcia Calavia Noelia , Malong Liza , Ribeiro Sara , Nihouarn Julie , Williams Richard , Young Kaylene M. , Richardson William D. , Lloyd Alison C.
Published: November 2018

Peripheral nerves are highly regenerative, in contrast to the poor regenerative capabilities of the central nervous system (CNS). Here, we show that adult peripheral nerve is a more quiescent tissue than the CNS, yet all cell types within a peripheral nerve proliferate efficiently following injury. Moreover, whereas oligodendrocytes are produced throughout life from a precursor pool, we find that the corresponding cell of the peripheral nervous system, the myelinating Schwann cell (mSC), does not turn over in the adult. However, following injury, all mSCs can dedifferentiate to the proliferating progenitor-like Schwann cells (SCs) that orchestrate the regenerative response. Lineage analysis shows that these newly migratory, progenitor-like cells redifferentiate to form new tissue at the injury site and maintain their lineage, but can switch to become a non-myelinating SC. In contrast, increased plasticity is observed during tumourigenesis. These findings show that peripheral nerves have a distinct mechanism for maintaining homeostasis and can regenerate without the need for an additional stem cell population.

This article has an associated ‘The people behind the papers’ interview.
Novel initiator caspase reporters uncover previously unknown features of caspase-activating cells
Authors: Baena-Lopez Luis Alberto , Arthurton Lewis , Bischoff Marcus , Vincent Jean-Paul , Alexandre Cyrille , McGregor Reuben
Published: November 2018

The caspase-mediated regulation of many cellular processes, including apoptosis, justifies the substantial interest in understanding all of the biological features of these enzymes. To complement functional assays, it is crucial to identify caspase-activating cells in live tissues. Our work describes novel initiator caspase reporters that, for the first time, provide direct information concerning the initial steps of the caspase activation cascade in Drosophila tissues. One of our caspase sensors capitalises on the rapid subcellular localisation change of a fluorescent marker to uncover novel cellular apoptotic events relating to the actin-mediated positioning of the nucleus before cell delamination. The other construct benefits from caspase-induced nuclear translocation of a QF transcription factor. This feature enables the genetic manipulation of caspase-activating cells and reveals the spatiotemporal patterns of initiator caspase activity. Collectively, our sensors offer experimental opportunities not available by using previous reporters and have proven useful to illuminate previously unknown aspects of caspase-dependent processes in apoptotic and non-apoptotic cellular scenarios.
Establishment of a murine culture system for modeling the temporal progression of cranial and trunk neural crest cell differentiation
Authors: Replogle Maria R. , Sreevidya Virinchipuram S. , Lee Vivian M. , Laiosa Michael D. , Svoboda Kurt R. , Udvadia Ava J.
Published: November 2018

The neural crest (NC) is a transient population of embryonic progenitors that are implicated in a diverse range of congenital birth defects and pediatric syndromes. The broad spectrum of NC-related disorders can be attributed to the wide variety of differentiated cell types arising from the NC. In vitro models of NC development provide a powerful platform for testing the relative contributions of intrinsic and extrinsic factors mediating NC differentiation under normal and pathogenic conditions. Although differentiation is a dynamic process that unfolds over time, currently, there is no well-defined chronology that characterizes the in vitro progression of NC differentiation towards specific cell fates. In this study, we have optimized culture conditions for expansion of primary murine NC cells that give rise to both ectodermal and mesoectodermal derivatives, even after multiple passages. Significantly, we have delineated highly reproducible timelines that include distinct intermediate stages for lineage-specific NC differentiation in vitro. In addition, isolating both cranial and trunk NC cells from the same embryos enabled us to make direct comparisons between the two cell populations over the course of differentiation. Our results define characteristic changes in cell morphology and behavior that track the temporal progression of NC cells as they differentiate along the neuronal, glial, and chondrogenic lineages in vitro. These benchmarks constitute a chronological baseline for assessing how genetic or environmental disruptions may facilitate or impede NC differentiation. Introducing a temporal dimension substantially increases the power of this platform for screening drugs or chemicals for developmental toxicity or therapeutic potential.
First-person Folk Psychology: Mindreading or Mindshaping?
Authors: De Bruin Leon
Published: November 2018

Proponents of mindshaping argue that third-person folk psychology (i.e., the ascription of mental states to others) is not primarily about "reading" mental states for the purpose of behavior prediction and explanation. Instead, they claim that third-person folk psychology is first and foremost a regulative practice -- one that "shapes" mental states in accordance with the norms of a shared folk psychological framework. This paper investigates to what extent the core assumptions behind the mindshaping hypothesis are compatible with an account of first-person folk psychology (i.e., the ascription of mental states to ourselves) that is based on the notion of "self-regulative agency."
Colorectal cancer
Authors: Peate Ian
Published: November 2018

This article in the series considers cancer of the large bowel; this type of cancer is often referred to as ‘colorectal’ cancer. Small bowel cancer is less common, as cancer is more likely to develop in the large bowel. The anatomy of the lower gastrointestinal tract is discussed; it is essential that the healthcare assistant and assistant practitioner (HCA and AP) have an understanding of the lower gastrointestinal tract in order to ensure the care they provide is appropriate and patient–centred.

The article outlines key issues associated with colorectal cancer. A glossary of terms is provided at the end of the article and five multiple–choice questions to help with learning and application to practice.
Managing chronic kidney disease in primary care
Authors: Rainey Helen
Published: November 2018

Chronic kidney disease is a common long-term condition often caused by diabetes or hypertension. It rarely causes symptoms in the early stages, but is associated with increased morbidity and mortality and may worsen to end stage kidney disease. The risks of complications can be reduced through early identification, good management and self-management. The number of guidelines relevant to this group of patients can be confusing and this article provides advice about the application of guidelines in practice. It also signposts readers to resources, which can be useful when planning individualised care with patients.
Encouraging treatment concordance in type 2 diabetes
Authors: Ferreira Christina Lange , Innes Emma
Published: November 2018

The purpose of this article is to reflect on the importance of education and patient involvement in the prescribing process in diabetes management. This article presents a case study of a patient with type 2 diabetes mellitus referred to the diabetes specialist nursing service due to long-standing poor glycaemic management, and reflects on clinical inertia and medicines optimisation. Using a case study from clinical practice, insights and recommendations can be made. This process enables knowledge transferability to be applied in diabetes consultations, affecting medicines optimisation and resistance of clinical inertia in the management of type 2 diabetes. Clinicians must strive to ensure patient involvement in the prescribing process. This case study supports the importance of conducting patient-centred medication reviews that support the patient's use their medicines. The importance of education regarding the treatments prescribed should not be underestimated and can impact on treatment concordance.
Nursing intertrigo in the dog
Authors: Paterson Sue
Published: November 2018

Intertrigo is a dermatitis caused by friction between two skin surfaces that are intimately apposed and rub against each other. Any skin fold can be affected but common sites include the lips, face, vulva, tail, neck and general body folds. In all cases, lesions are characterised by erythema, exudation and a malodorous discharge. Cytology of lesions is easily achieved and is essential in the selection of appropriate topical therapy. In severe cases, surgery may be necessary to remove the fold.
Spaying bitches: why, when, how?
Authors: Hoad Julian G
Published: November 2018

Spaying is one of the most commonly performed surgical procedures in the UK, and yet there is little in the way of consistency among practices in the advice given to owners wishing to have their bitch neutered. Opinions are often conflicting in terms of pros and cons of spaying, timing of spaying and whether the uterus and ovaries should be removed, or just the ovaries. This article considers some of the available evidence and tries to resolve some of the ambiguity where possible.
Editorial
Authors: Allison Katherine
Published: November 2018

To download this paper, please click here.
Review: The Fantastic Worlds of Yuri Vynnychuk (2016)
Authors: Kernan Helena
Published: November 2018

To download a copy of this review, click here.
Correlation of Serum Magnesium with Dyslipidemia in Maintenance Hemodialysis Patients
Authors: Nasri Hamid , Baradaran Azar
Published: November 2018

One of the factors involved in accelerated atherosclerosis in hemodialysis patients is dyslipidemia. In this study we considered factors involved in intensification of dyslipidemia in hemodialysis patients.This study was done on 36 maintenance hemodialysis patients. Serum lipoprotein (a), Triglyceride, Cholesterol, HDL-C,LDL-C and also serum Intact parathormone( iPTH), Calcium, Phosphorus, Magnesium were measured. In statistical analysis there was not any correlation between serum lipids and iPTH. There was not correlation between serum calcium with serum lipids (p>0.05). There was not correlation between CaxP product with serum lipids (p>0.05). There was a positive correlation between serum Magnesium and Lipoprotein(a) (P<0.05) and also positive correlation between serum magnesium with triglyceride level (P<0.05) was seen too. Magnesium doesn’t increase the lipoprotein synthesis. It may involve in the regulation of some enzymes responsible for lipoprotein synthesis. Correlation of serum magnesium with serum triglycerides can be due to changes in hepatic triglyceride metabolism. Lipoprotein(a) is a non traditional factor of premature atherosclerosis, its association with serum magnesium needs more attention in hemodialysis patients.
Natal and Neonatal Teeth
Authors: Seminario Ana Lucía , Ivančaková Romana
Published: November 2018

Tooth eruption follows a chronology corresponding to the date when the tooth erupts into the oral cavity. This date has been established in the literature and is subject to small variations depending on hereditary, endocrine and environmental features. Any disturbance during the development of the teeth -systemic or local- can affect not only the morphology, structure of dental hard tissues or number of teeth but also the time of eruption. The presence of a tooth in the mouth at birth or during the first month of life has been studied and denominated as natal and neonatal teeth. The aim of this paper is to review current information on this topic and to give treatment alternatives if it is necessary.
Orchestrating learning analytics (OrLA): Supporting inter-stakeholder communication about adoption of learning analytics at the classroom level
Authors: Prieto Luis P. , Rodríguez-Triana María Jesús , Martínez-Maldonado Roberto , Dimitriadis Yannis , Gašević Dragan
Published: November 2018

Despite the recent surge of interest in learning analytics (LA), their adoption in everyday classroom practice is still slow. Knowledge gaps and lack of inter-stakeholder communication (particularly with educational practitioners) have been posited as critical factors for previous LA adoption failures. Yet, what issues should researchers, practitioners and other actors communicate about, when considering the adoption of an LA innovation in a particular context? We reviewed and synthesised existing literature on four focus areas related to LA, their adoption, implications for practice, and more general factors that have emerged as crucial when studying everyday classroom adoption of technologies (i.e., classroom orchestration). This synthesis resulted in two conversational frameworks and an inter-stakeholder communication tool. These can be used to guide and support conversations and decision-making about the adoption of LA innovations. We illustrate their usefulness with examples of use in ongoing LA adoption processes in Australia, Spain and Estonia.
Krwawa karuzela (Władimir Zazubrin, „Drzazga”)
Authors: Zywert Aleksandra
Published: November 2018

This article presents a comparative analysis of Vladimir Zazubrin’s story titled The Splinter (1923) and its contemporary screen adaptation, i.e. Alexandr Rogozhkin’s film The Chekist (1992), in the context of the Russian nation’s tragedy during the formation of a new socio-political system. Just as Zazubrin text is a peculiar testimony to a certain epoch, Rogozhkin’s film (if one also takes into account the date of its premiere) is a picture that warns contemporary people so as to prevent them from repeating their predecessors’ mistakes.
Литература как миф и гипертекст в „Бесконечном тупике” Дмитрия Галковского (к реконструкции историософской модели)
Authors: Szubin Roman
Published: November 2018

This article is devoted to reconstruction of the historiosophical concept in Dmitry Galkovsky's novel The Infinite Deadlock (Бесконечный тупик). The author pays particular attention to the criteria of historiosophy: mythologism, ambivalence of consciousness, hesychast tradition, eidetic language, a universal man (absolute personality). He highlights the demythological factor in Galkovsky's creative work, its cultural and national nihilism. The author analyzes the image of the main character's identity, who is capable of identifying himself, who is humiliated or ingenious. In passing, the author considers the idea of common history in which the eras which dialectically deny each other's coexistence.
Омографические триады в русском языке
Authors: Kaliszan Jerzy
Published: November 2018

The article is devoted to the study of Russian homographic rows consisting of three components, such as ворона (gen. and acc. sg. of ворон ‘raven’) — ворона (nom. sg.) ‘crow’ — ворона (short form of вороной ‘black’), вертела (gen. sg. of вертел ‘spit for roasting’) — вертела (nom. and acc. pl. of вертел) — вертела (past of вертеть ‘to turn’), здорово (adv.) ‘greatly, superbly; hard, strongly’ — здорово (short neut. form of здоровый I ‘healthy’) — здорово (short neut. form of здоровый II ‘tremendous, hefty’). The author has analyzed and classified 70 such three-component groups of homographs revealed in contemporary Russian.
„Lajki” i „hejty”, czyli kilka słów o socjolekcie polskich i rosyjskich użytkowników internetu
Authors: Kuligowska Katarzyna
Published: November 2018

The author presents several psycho- and sociolinguistic phenomena connected with Internet use. An analysis of the sociolect of Polish and Russian Internet users allows the author to establish the main kinds of human activity in the Internet and what the impact that using the Internet has on the individual.
Дискуссия как один из методов проблемного обучения
Authors: Dziewanowska Dorota
Published: November 2018

The author of the article points out the advantages of using the discussion method (which is one of the strategies of problem teaching) during foreign language classes. This strategy creates the possibility to develop various competences in learners, for example: the competence of formulating their own opinion; the competence of expressing their point of view; the competence of achieving consensus and formulating decisions reached through solving the problem together with a group of learners; the competence  of summing up. In the process of foreign language teaching, discussion is the most effective and also the most complicated form of language practice, and one which requires multi-stage preparation.
Limited response of a spring bloom community inoculated with filamentous cyanobacteria to elevated temperature and pCO2
Authors: Olofsson Malin , Torstensson Anders , Karlberg Maria , Steinhoff Franciska S. , Dinasquet Julie , Riemann Lasse , Chierici Melissa , Wulff Angela
Published: November 2018

Temperature and CO2 levels are projected to increase in the future, with consequences for carbon and nutrient cycling in brackish environments, such as the Baltic Sea. Moreover, filamentous cyanobacteria are predicted to be favored over other phytoplankton groups under these conditions. Under a 12-day outdoor experiment, we examined the effect on a natural phytoplankton spring bloom community of elevated temperature (from 1°C to 4°C) and elevated pCO2 (from 390 to 970 μatm). No effects of elevated pCO2 or temperature were observed on phytoplankton biovolumes, but a significantly higher photosystem II activity was observed at elevated temperature after 9 days. In addition, three species of diazotrophic filamentous cyanobacteria were inoculated to test their competitive capacity under spring bloom conditions. The toxic cyanobacterium Nodularia spumigena exhibited an average specific growth rate of 0.10 d−1 by the end of the experiment, indicating potential prevalence even during wintertime in the Baltic Sea. Generally, none of the inoculated cyanobacteria species were able to outcompete the natural phytoplankton species at temperatures ≤4°C. No direct effects were found on heterotrophic bacteria. This study demonstrates the highly efficient resistance towards short-term (12 days) changes in abiotic factors by the natural Baltic Sea spring bloom community.
Approximation solvability for a system of implicit nonlinear variational inclusions with Η-monotone operators
Authors: Kim Jong Kyu , Bhat Muhammad Iqbal
Published: November 2018

In this paper, we introduce and study a new system of variational inclusions which is called a system of nonlinear implicit variational inclusion problems with A-monotone and H-monotone operators in semi-inner product spaces. We define the resolvent operator associated with A-monotone and H-monotone operators and prove its Lipschitz continuity. Using resolvent operator technique, we prove the existence and uniqueness of solution for this new system of variational inclusions. Moreover, we suggest an iterative algorithm for approximating the solution of this system and discuss the convergence analysis of the sequences generated by the iterative algorithm under some suitable conditions.
Pack-Boriding of Pure Iron with Powder Mixtures Containing ZrB2
Authors: Calik A. , Ucar N. , Karakas M.S. , Tanis H.
Published: November 2018

Boriding of pure iron was investigated using the powder pack method with boriding powder mixtures containing different weight fractions of ZrB2 (5 %, 10 %, 15 % and 20 %). The samples were borided in an electric resistance furnace for an exposure time of 4 h at 1,173 K temperature under atmospheric pressure. Borided samples were characterized by optical microscopy, X-ray diffraction analyses and microhardness tests. Results showed that the boride layers consisted mainly of FeB and Fe2B phases. No significant difference in boride layer thicknesses (average 140 μm) could be observed as a function of ZrB2 content. The needle-like morphology of the boride layer became more prominent with increasing weight fraction of ZrB2 in the boriding powders. The average microhardness of the boride layer decreased with increasing ZrB2 content due to changes in the morphology of the boride layer.
The Blood brain-barrier and its role in Alzheimer’s disease
Authors: Storck Steffen E. , Pietrzik Claus U.
Published: November 2018

The blood brain-barrier (BBB), built up by the interaction of different cell types in vessels of the brain, is essential for brain homeostasis. As a gatekeeper of the central nervous system (CNS), the BBB controls the exchange of molecules between brain and blood. In many neurodegenerative diseases including Alzheimer’s disease (AD) the BBB show alterations which impair brain function and promote neurodegeneration. As an important elimination route for neurotoxic amyloid-beta (Aβ), the BBB is crucial for the healthy brain by regulating the concentration of soluble Aβ in the interstitial fluid (ISF) in the brain. Here, we discuss the composition and distinctive physiological features of CNS vasculature and the pathological alterations that are present in AD and disturb BBB function.
Meinong’s Multifarious Being and Russell’s Ontological Variable: Being in Two Object Theories across Traditions at the Turn of the 20th Century
Authors: Pribram-Day Ivory
Published: November 2018

This paper discusses the problems of an ontological value of the variable in Russell’s philosophy. The variable is essential in Russell’s theory of denotation, which among other things, purports to prove Meinongian being outside of subsistence and existence to be logically unnecessary. I argue that neither Russell’s epistemology nor his ontology can account for the ontological value of the variable without running into qualities of Meinongian being that Russell disputed. The problem is that the variable cannot be logically grounded by Russell’s theory of denotation. As such, in so far as being is concerned, Meinong and Russell’s theories are much closer than is typically thought. The arguments are supported with concerns raised by Russell, Frege, and Moore regarding the ontological value of the variable. The problem can be summarised as follows: the variable is the fundamental denoting-position of a formal theory that is meant to explain the structure of the ontological. If such a formal theory is meant to ground the ontological, then the formal must also represent the actual structure of the ontological. Yet the variable, the fundamental symbol of denotation in a theory that defines objects, is ontologically indefinable.