bluuebunny/crossref_metadata_2025 huggingface dataset:
Azithromycin inhibits muscarinic 2 receptor‐activated and voltage‐activated Ca2+ permeant ion channels and Ca2+ sensitization, relaxing airway smooth muscle contraction
Authors: Wang Qian , Yu Meng‐Fei , Zhang Wen‐Jing , Liu Bei‐Bei , Zhao Qing‐Yang , Luo Xi , Xu Hao , She Yu‐Shan , Zang Dun‐An , Qiu Jun‐Ying , Shen Jinhua , Peng Yong‐Bo , Zhao Ping , Xue Lu , Chen Weiwei , Ma Li‐Qun , Nie Xiaowei , Shen Chenyou , Chen Shu , Chen Shanshan , Liu Quan , Dai Jiapei , Qin Gangjian , Zheng Yun‐min , Wang Yong‐Xiao , ZhuGe Ronghua , Chen Jingyu , Liu Qing‐Hua
Published: January 2019

Azithromycin (AZM) has been used for the treatment of asthma and chronic obstructive pulmonary disease (COPD); however, the effects and underlying mechanisms of AZM remain largely unknown. The effects of AZM on airway smooth muscles (ASMs) and the underlying mechanisms were studied using isometric muscle force measurements, the examination of lung slices, imaging, and patch‐clamp techniques. AZM completely inhibited acetylcholine (ACH)‐induced precontraction of ASMs in animals (mice, guinea pigs, and rabbits) and humans. Two other macrolide antibiotics, roxithromycin and Klaricid, displayed a decreased inhibitory activity, and the aminoglycoside antibiotics penicillin and streptomycin did not have an inhibitory effect. Precontractions were partially inhibited by nifedipine (selective inhibitor of L‐type voltage‐dependent Ca2+ channels (LVDCCs)), Pyr3 (selective inhibitor of TRPC3 and/or STIM/Orai channels, which are nonselective cation channels (NSCCs)), and Y‐27632 (selective inhibitor of Rho‐associated kinase (ROCK)). Moreover, LVDCC‐ and NSCC‐mediated currents were inhibited by AZM, and the latter were suppressed by the muscarinic (M) 2 receptor inhibitor methoctramine. AZM inhibited LVDCC Ca2+ permeant ion channels, M2 receptors, and TRPC3 and/or STIM/Orai, which decreased cytosolic Ca2+ concentrations and led to muscle relaxation. This relaxation was also enhanced by the inhibition of Ca2+ sensitization. Therefore, AZM has potential as a novel and potent bronchodilator. The findings of this study improve the understanding of the effects of AZM on asthma and COPD.
Multi‐observer contouring of male pelvic anatomy: Highly variable agreement across conventional and emerging structures of interest
Authors: Roach Dale , Holloway Lois C , Jameson Michael G , Dowling Jason A , Kennedy Angel , Greer Peter B , Krawiec Michele , Rai Robba , Denham Jim , De Leon Jeremiah , Lim Karen , Berry Megan E , White Rohen T , Bydder Sean A , Tan Hendrick T , Croker Jeremy D , McGrath Alycea , Matthews John , Smeenk Robert J , Ebert Martin A
Published: January 2019

Introduction

This study quantified inter‐observer contouring variations for multiple male pelvic structures, many of which are of emerging relevance for prostate cancer radiotherapy progression and toxicity response studies.

Methods

Five prostate cancer patient datasets (CT and T2‐weighted MR) were distributed to 13 observers for contouring. CT structures contoured included the clinical target volume (CTV), seminal vesicles, rectum, colon, bowel bag, bladder and peri‐rectal space (PRS). MR contours included CTV, trigone, membranous urethra, penile bulb, neurovascular bundle and multiple pelvic floor muscles. Contouring variations were assessed using the intraclass correlation coefficient (ICC), Dice similarity coefficient (DSC), and multiple additional metrics.

Results

Clinical target volume (CT and MR), bladder, rectum and PRS contours showed excellent inter‐observer agreement (median ICC = 0.97; 0.99; 1.00; 0.95; 0.90, DSC = 0.83 ± 0.05; 0.88 ± 0.05; 0.93 ± 0.03; 0.81 ± 0.07; 0.80 ± 0.06, respectively). Seminal vesicle contours were more variable (ICC = 0.75, DSC = 0.73 ± 0.14), while colon and bowel bag contoured volumes were consistent (ICC = 0.97; 0.97), but displayed poor overlap (DSC = 0.58 ± 0.22; 0.67 ± 0.21). Smaller MR structures showed significant inter‐observer variations, with poor overlap for trigone, membranous urethra, penile bulb, and left and right neurovascular bundles (DSC = 0.44 ± 0.22; 0.41 ± 0.21; 0.66 ± 0.21; 0.16 ± 0.17; 0.15 ± 0.15). Pelvic floor muscles recorded moderate to strong inter‐observer agreement (ICC = 0.50–0.97), although large outlier variations were observed.

Conclusions

Inter‐observer contouring variation was significant for multiple pelvic structures contoured on MR.
sFRP3 inhibition improves age‐related cellular changes in BubR1 progeroid mice
Authors: Cho Chang Hoon , Yoo Ki Hyun , Oliveros Alfredo , Paulson Summer , Hussaini Syed Mohammed Qasim , van Deursen Jan M. , Jang Mi‐Hyeon
Published: January 2019

Wnt signaling is a well‐known molecular pathway in age‐related pathogenesis and therapy of disease. While prior studies have mainly focused on Wnt ligands or Wnt activators, the in vivo functions of naturally secreted Wnt inhibitors are not clear, especially in brain aging. Using BubR1H/H mice as a novel mouse model of accelerated aging, we report that genetic inhibition of sFRP3 restores the reduced body and brain size observed in BubR1H/H mice. Furthermore, sFRP3 inhibition ameliorates hypomyelination in the corpus callosum and rescues neural progenitor proliferation in the hippocampal dentate gyrus of BubR1H/H mice. Taken together, our study identifies sFRP3 as a new molecular factor that cooperates with BubR1 function to regulate brain development, myelination, and hippocampal neurogenesis.
Dying under pressure: cellular characterisation and in vivo functions of cell death induced by compaction
Authors: Valon Léo , Levayer Romain
Published: January 2019

Cells and tissues are exposed to multiple mechanical stresses during development, tissue homoeostasis and diseases. While we start to have an extensive understanding of the influence of mechanics on cell differentiation and proliferation, how excessive mechanical stresses can also lead to cell death and may be associated with pathologies has been much less explored so far. Recently, the development of new perturbative approaches allowing modulation of pressure and deformation of tissues has demonstrated that compaction (the reduction of tissue size or volume) can lead to cell elimination. Here, we discuss the relevant type of stress and the parameters that could be causal to cell death from single cell to multicellular systems. We then compare the pathways and mechanisms that have been proposed to influence cell survival upon compaction. We eventually describe the relevance of compaction‐induced death in vivo, and its functions in morphogenesis, tissue size regulation, tissue homoeostasis and cancer progression.
Neuronal sub‐compartmentalization: a strategy to optimize neuronal function
Authors: Donato Alessandra , Kagias Konstantinos , Zhang Yun , Hilliard Massimo A.
Published: January 2019

Neurons are highly polarized cells that consist of three main structural and functional domains: a cell body or soma, an axon, and dendrites. These domains contain smaller compartments with essential roles for proper neuronal function, such as the axonal presynaptic boutons and the dendritic postsynaptic spines. The structure and function of these compartments have now been characterized in great detail. Intriguingly, however, in the last decade additional levels of compartmentalization within the axon and the dendrites have been identified, revealing that these structures are much more complex than previously thought. Herein we examine several types of structural and functional sub‐compartmentalization found in neurons of both vertebrates and invertebrates. For example, in mammalian neurons the axonal initial segment functions as a sub‐compartment to initiate the action potential, to select molecules passing into the axon, and to maintain neuronal polarization. Moreover, work in Drosophila melanogaster has shown that two distinct axonal guidance receptors are precisely clustered in adjacent segments of the commissural axons both in vivo and in vitro, suggesting a cell‐intrinsic mechanism underlying the compartmentalized receptor localization. In Caenorhabditis elegans, a subset of interneurons exhibits calcium dynamics that are localized to specific sections of the axon and control the gait of navigation, demonstrating a regulatory role of compartmentalized neuronal activity in behaviour. These findings have led to a number of new questions, which are important for our understanding of neuronal development and function. How are these sub‐compartments established and maintained? What molecular machinery and cellular events are involved? What is their functional significance for the neuron? Here, we reflect on these and other key questions that remain to be addressed in this expanding field of biology.
Towards a ‘Sea‐Level Sensitive’ dynamic model: impact of island ontogeny and glacio‐eustasy on global patterns of marine island biogeography
Authors: Ávila Sérgio P. , Melo Carlos , Berning Björn , Sá Nuno , Quartau Rui , Rijsdijk Kenneth F. , Ramalho Ricardo S. , Cordeiro Ricardo , De Sá Nuno C. , Pimentel Adriano , Baptista Lara , Medeiros António , Gil Artur , Johnson Markes E.
Published: January 2019

A synthetic model is presented to enlarge the evolutionary framework of the General Dynamic Model (GDM) and the Glacial Sensitive Model (GSM) of oceanic island biogeography from the terrestrial to the marine realm. The proposed ‘Sea‐Level Sensitive’ dynamic model (SLS) of marine island biogeography integrates historical and ecological biogeography with patterns of glacio‐eustasy, merging concepts from areas as diverse as taxonomy, biogeography, marine biology, volcanology, sedimentology, stratigraphy, palaeontology, geochronology and geomorphology. Fundamental to the SLS model is the dynamic variation of the littoral area of volcanic oceanic islands (defined as the area between the intertidal and the 50‐m isobath) in response to sea‐level oscillations driven by glacial–interglacial cycles. The following questions are considered by means of this revision: (i) what was the impact of (global) glacio‐eustatic sea‐level oscillations, particularly those of the Pleistocene glacial–interglacial episodes, on the littoral marine fauna and flora of volcanic oceanic islands? (ii) What are the main factors that explain the present littoral marine biodiversity on volcanic oceanic islands? (iii) How can differences in historical and ecological biogeography be reconciled, from a marine point of view? These questions are addressed by compiling the bathymetry of 11 Atlantic archipelagos/islands to obtain quantitative data regarding changes in the littoral area based on Pleistocene sea‐level oscillations, from 150 thousand years ago (ka) to the present. Within the framework of a model sensitive to changing sea levels, we discuss the principal factors affecting the geographical range of marine species; the relationships between modes of larval development, dispersal strategies and geographical range; the relationships between times of speciation, modes of larval development, ecological zonation and geographical range; the influence of sea‐surface temperatures and latitude on littoral marine species diversity; the effect of eustatic sea‐level changes and their impact on the littoral marine biota; island marine species–area relationships; and finally, the physical effects of island ontogeny and its associated submarine topography and marine substrate on littoral biota. Based on the SLS dynamic model, we offer a number of predictions for tropical, subtropical and temperate volcanic oceanic islands on how rates of immigration, colonization, in‐situ speciation, local disappearance, and extinction interact and affect the marine biodiversity around islands during glacials and interglacials, thus allowing future testing of the theory.
Parvovirus infection and its treatment
Authors: Young N S
Published: January 2019

B19 parvovirus is an important pathogen in man. Acute infection produces fifth disease (erythema infectiosum) in normal individuals, transient aplastic crisis in the patient with haemolysis, and pure red cell aplasia in the immunologically incompetent host. Fetal infection can lead to hydrops fetalis. The target cell of the virus is the marrow erythroid progenitor. The immune response to the virus is largely humoral and directed against limited numbers of epitopes. Persistent infection is due to failure to produce neutralizing antibodies. Because viral infection is prevalent in the population, therapeutic immune globulin preparations arc a good source of anti-B19 antibodies. IgG administration can lead to cure of anaemia in the congenitally immunodeficient patient and to its amelioration in AIDS patients with persistent parvovirus infection.
Intravenous immune globulin in multiple sclerosis: clinical and neuroradiological results and implications for possible mechanisms of action
Authors: Achiron A , Barak Y , Goren M , Gabbay U , Miron S , Rotstein Z , Noy S , Sarova-Pinhas I
Published: January 2019

Extensive evidence exists indicating that immunoregulatory mechanisms are involved in the pathogenesis of Multiple Sclerosis (MS). Several possible mechanisms by which intravenous immune globulin (IVIG) modulates the course of the disease are related to limiting the inflammatory process and repairing the damage by enhancing remyelination. Presently, the evidence for the effect of IVIG in MS is based on the results of small open trials, some of which have been encouraging. In the current study, the positive impact of IVIG treatment on arresting disease progression was evident by decreased brain Magnetic Resonance Imaging (MRI) scores of the lesion area. In an effort to extend these findings, the authors initiated a multicentre, prospective, randomized, double-blind, placebo-controlled study. The trial was designed to compare the ellicacy of IVIG treatment with placebo in relapsing-remitting patients (ages 20–55 years) with definite MS, disease duration of 210 years and frequency of exacerbations 1–3/year during the 2 years prior to the study. Patients were examined monthly and brain MRI studies scheduled at entry, and after the first and second years of the trial. The primary endpoints included the number of acute exacerbations and neurological disability. The secondary endpoints included change in the MRI lesion burden, evaluated by the number and area of lesions. The trial ended in June 1995.
Supplemental immune globulins in sepsis: a critical appraisal
Authors: Werdan K , Pilz G
Published: January 2019

For ‘the total population of patients with sepsis, sepsis syndrome or SIRS’, the question of whether intravenous immune globulin (IVIG) reduces mortality is neither proved nor disproved. For the sepsis subgroups ‘postoperative sepsis with a sepsis score > 19’ and ‘endotoxaemic, early septic shock’, a significant reduction in mortality by IVIG has been documented in a single, placebo-controlled, small trial of each subgroup; subsequent studies are needed for confirmation. The incidence of some severe infections in defined 'patients at risk’ and ‘operations at risk’ is lowered by IVIG prophylaxis. Postoperative APACHE II-score identification of high-risk cardiac surgery patients prone to sepsis and severe SIRS may represent one approach to optimize individual, early therapy. Applying this concept to immune globulin treatment in a pilot study, the administration of IgG-IVIG and IgGMA-IVIG yielded similar results.
Implant health and factors affecting peri‐implant marginal bone alteration for implants placed in staged maxillary sinus augmentation: A 5‐year prospective study
Authors: Krennmair Stefan , Hunger Stefan , Forstner Thomas , Malek Michael , Krennmair Gerald , Stimmelmayr Michael
Published: January 2019

Purpose

Evaluating the extent of and the factors affecting marginal bone level (MBL) alterations and consecutively implant success and implant health for implants placed in staged maxillary sinus floor (SF) augmentation.

Materials and Methods

A 5‐year prospective, cohort study was conducted on 85 patients with 124 maxillary sinus augmentation procedure and 295 implants placed. Peri‐implant MBL alterations (reductions) were evaluated radiographically at the first year, third year, and fifth year postloading follow‐ups and were considered to patient‐related risk factors (age, gender, diabetes mellitus, smoking, rheumatic disorders, and history of periodontal disease [PD]), to clinican/surgically related risk factors (membrane perforations, sinus site, and residual ridge height), to implant/prosthesis‐related features (implant length, diameter, location, keratinized gingiva, and restoration gap), and to the plaque score. Additionally, implant and prostheses survival/success rate and peri‐implant health (mucositis/peri‐implantitis) were assessed.

Results

About 267/295 implants (drop‐out:n9 pat; 28 implants: 9%) were followed for 5 years (survival/success: 99.3%/96.5%), presenting significant (P < .001) differences of MBL alterations (−1.45 ± 0.38 mm) over time. The univariate analysis demonstrated differences of MBL alterations for smokers versus nonsmokers (P = .005), for patients with versus without history of PD (P = .001), and presence versus absence of plaque (P = .041). In the 5‐year multivariate analysis, MBL alteration was influenced by time (P = .001) and was related to risk factors as smoking (P = .001; odds ratio [OR] = 6.563) and history of PD (P = .015; OR = 4.450). Significant ORs for MBL alterations were also found for a restoration gap used for a full‐arch dentures (P = .001; OR = 8.275) associated with reduced (≤3 mm) residual ridge height (P = .015; OR = 1.365). The overall 5 year incidence of peri‐implant mucositis and peri‐implantitis was 25.3% and 3.7% at implant level and 30.3% and 6.6% at patient level, respectively.

Conclusions

Apart from the high success rate and healthy status of implant placed in staged SF seen, MBL alteration increased over time and was negatively affected predominately by patient‐specific risk factors such as smoking status and previous history of periodontitis.
Double‐blind, randomized clinical trial assessing the efficacy and safety of early initiation of sitagliptin during metformin uptitration in the treatment of patients with type 2 diabetes: The CompoSIT‐M study
Authors: Frias Juan P. , Zimmer Zachary , Lam Raymond L.H. , Amorin Guillermo , Ntabadde Catherine , Iredale Carol , O'Neill Edward A. , Engel Samuel S. , Kaufman Keith D. , Makimura Hideo , Crutchlow Michael F.
Published: January 2019

Aims

To characterize the glycaemic efficacy and safety of initiation of the dipeptidyl peptidase‐4 inhibitor sitagliptin during metformin dose escalation in people with type 2 diabetes (T2D) not at glycated haemoglobin (HbA1c) goal on a sub‐maximal dose of metformin.

Materials and methods

Study participants with HbA1c ≥58 mmol/mol and ≤97 mmol/mol (≥7.5% and ≤11.0%) while on 1000 mg/d metformin were randomized to sitagliptin 100 mg once daily or placebo. All were to uptitrate metformin to 2000 mg/d. A longitudinal data analysis model was used to test the primary hypothesis that sitagliptin is superior to placebo when initiated during uptitration of metformin in reducing HbA1c at week 20. [ClinicalTrials.gov Identifier: NCT02791490, EudraCT: 2015‐004224‐59]

Results

A total of 458 participants (mean HbA1c 71.1 mmol/mol [8.7%], T2D duration 6.3 years) were treated. After 20 weeks, the least squares (LS) mean changes from baseline in HbA1c were −12.1 mmol/mol (−14.0, −10.1) (−1.10% [−1.28, −0.93]) and −7.6 mmol/mol (−9.6, −5.6) (−0.69% [−0.88, −0.51]) with sitagliptin and placebo, respectively; the between‐group difference in LS mean changes from baseline HbA1c was −4.5 mmol/mol (−6.5, −2.5) (−0.41% [−0.59, −0.23]); P < 0.001. The likelihood of having HbA1c <53 mmol/mol (<7.0%) at week 20 was higher in the sitagliptin group than in the placebo group in the overall population (relative risk 1.7, P = 0.002) and in those with a baseline HbA1c ≥69 mmol/mol (≥8.5%) (relative risk 2.4, P = 0.026). There were no notable differences between groups with regard to adverse events overall, hypoglycaemia events, changes in body weight or other safety variables.

Conclusion

In participants not at HbA1c goal on a sub‐maximal dose of metformin, addition of sitagliptin at the time of metformin dose uptitration improved glycaemic response and HbA1c goal attainment, with similar safety and tolerability, compared to metformin uptitration alone.
Seizure‐induced microvascular injury is associated with impaired neurovascular coupling and blood–brain barrier dysfunction
Authors: Prager Ofer , Kamintsky Lyna , Hasam‐Henderson Luisa A. , Schoknecht Karl , Wuntke Vera , Papageorgiou Ismini , Swolinsky Jutta , Muoio Valeria , Bar‐Klein Guy , Vazana Udi , Heinemann Uwe , Friedman Alon , Kovács Richard
Published: January 2019

Objective

Blood–brain barrier (BBB) impairment, redistribution of pericytes, and disturbances in cerebral blood flow may contribute to the increased seizure propensity and neurological comorbidities associated with epilepsy. However, despite the growing evidence of postictal disturbances in microcirculation, it is not known how recurrent seizures influence pericytic membrane currents and subsequent vasodilation.

Methods

Here, we investigated successive changes in capillary neurovascular coupling and BBB integrity during recurrent seizures induced by 4‐aminopyridine or low‐Mg2+ conditions. To avoid the influence of arteriolar dilation and cerebral blood flow changes on the capillary response, we measured seizure‐associated pericytic membrane currents, capillary motility, and permeability changes in a brain slice preparation. Arteriolar responses to 4‐aminopyridine–induced seizures were further studied in anesthetized Sprague Dawley rats by using electrocorticography and tissue oxygen recordings simultaneously with intravital imaging of arteriolar diameter, BBB permeability, and cellular damage.

Results

Within the preserved vascular network in hippocampal slice cultures, pericytes regulated capillary diameter in response to vasoactive agents and neuronal activity. Seizures induced distinct patterns of membrane currents that contributed to the regulation of pericytic length. During the course of recurrent seizures, individual vasodilation responses eroded and BBB permeability increased, despite unaltered neurometabolic coupling. Reduced vascular responsiveness was associated with mitochondrial depolarization in pericytes. Subsequent capillary constriction preceded BBB opening, suggesting that pericyte injury mediates the breach in capillary integrity. In vivo findings were consistent with slice experiments, showing seizure‐related neurovascular decoupling and BBB dysfunction in small cortical arterioles, accompanied by perivascular cellular injury despite normoxic conditions.

Significance

Our study presents a direct observation of gradually developing neurovascular decoupling during recurrent seizures and suggests pericytic injury as an inducer of vascular dysfunction in epilepsy.
Strontium plesiotherapy for the treatment of sarcoids in the horse
Authors: Hollis A. R.
Published: January 2019

Sarcoids are a common condition in the horse. They are often difficult to treat and there is no universally effective treatment method. Radiotherapy is the most consistently successful treatment and plesiotherapy may be effective for carefully selected sarcoid lesions. The objective of this retrospective clinical case series was to describe the response rate and safety of strontium plesiotherapy for the treatment of equine sarcoids. Horses and ponies referred for strontium treatment of sarcoids were eligible for inclusion in the study and diagnosis was based solely on the clinical features. Horses were given a total tumour dose of 100 Gy under either standing sedation or general anaesthesia, depending on the accessibility of the lesion. Eight horses with 10 sarcoids were treated with strontium plesiotherapy. Follow‐up was available for between 6 and 30 months after treatment. Complete resolution occurred in all cases. No significant short or long‐term adverse effects were noted apart from local leucotrichia, leukoderma and hair loss. The major limitations of this study are the lack of long‐term follow‐up and the small number of horses. It was concluded that strontium plesiotherapy appears to be an effective and safe method of treating selected equine sarcoids. This is a useful alternative for lesions in areas difficult to treat with other methods or where other methods have been unsuccessful. Longer term follow‐up is required to determine the risk of recurrence of treated lesions.
Potential trade‐offs of employing perennial biomass crops for the bioeconomy in the EU by 2050: Impacts on agricultural markets in the EU and the world
Authors: Choi Hyung Sik , Grethe Harald , Entenmann Steffen K. , Wiesmeth Michael , Blesl Markus , Wagner Moritz
Published: January 2019

Perennial biomass crops (PBC) are considered a crucial feedstock for sustainable biomass supply to the bioeconomy that compete less with food production compared to traditional crops. However, large‐scale development of PBC as a means to reach greenhouse gas (GHG) mitigation targets would require not only the production on land previously not used for agriculture, but also the use of land that is currently used for agricultural production. This study aims to evaluate agricultural market impacts with biomass demand for food, feed, and PBC in four bioeconomy scenarios (“Business as usual,” “Improved relevance of bioeconomy,” “Extensive transformation to a bioeconomy,” “Extensive transformation to a bioeconomy with diet change”) to achieve a 75% GHG reduction target in the emission trading sector of the EU until 2050. We simulated bioeconomy scenarios in the energy system model TIMES‐PanEU and the agricultural sector model ESIM and conducted a sensitivity analysis considering crop yields, PBC yields, and land use options of PBC. Our results show that all bioeconomy scenarios except the one with diet change lead to increasing food prices (the average food price index increases by about 11% in the EU and 2.5%–3.0% in world markets). A combination of the transformation to a bioeconomy combined with diet change toward less animal protein in the EU is the only scenario that results in only moderately increasing food prices within the EU (+3.0%) and even falling global food prices (–6.4%). In addition, crop yield improvement and cultivation of PBC on marginal land help to reduce increases in food prices, but higher land prices are inevitable because those measures have only small effects on sparing agricultural land for PBC. For a transition to a bioeconomy that acknowledges climate mitigation targets, counter‐measures for those substantial direct and indirect impacts on agricultural markets should be taken into account.
Detailed pathological analysis of the advancing edge of the tumour can effectively stratify clinical T4b colorectal cancer patients
Authors: Kim So‐Woon , Kim Jiyoon , Hong Seung‐Mo , Yoon Yong Sik , Park In Ja , Yu Chang Sik , Kim Jihun
Published: January 2019

Aims

Pathological staging of colorectal cancers (CRCs) that involve adhesion to adjacent organs (clinical stages T4b, cT4b) is sometimes difficult because the morphology of the invasive front varies. To resolve this issue, we reviewed 492 surgically resected CRC samples, comprising 96 cT4b tumours and, for comparison, 335 typical pathological stages (p) T3 and 61 pT4a tumours.

Methods and results

Cases were subdivided into four groups according to the presence or absence of microscopic tumour invasion into the muscular wall of the adjacent organs and peritumoral abscess along invasive front. Those that directly invaded the wall of the adjacent organs without peritumoral abscess were associated with a significantly worse overall (OS) and recurrence‐free survival (RFS) than the other three types of cT4b tumours. Those with peritumoral abscess showed similar prognosis to typical pT3 tumours, even when the advancing edge of the tumour invaded the wall of adjacent organs (staged as pT4b). Tumours showing fibrous adhesions without tumour cell invasion into the muscular wall of the adjacent organs showed a similar prognosis to typical pT3 tumours and showed a better prognosis than pT4a tumours.

Conclusion

Only CRCs with tumour cell invasion into the muscular wall of the adjacent organs should be classified as pT4b, and it might be better to avoid ‘the presence of tumour cells in fibrous adhesion' to define pathological T4b CRCs. In addition, the presence of a peritumoral abscess should be recorded as a predictor of better prognosis.
An investigation into green coffee press cake as a renewable source of bioactive compounds
Authors: Resende Oliveira Érica , Fonseca da Silva Rodrigo , Ribeiro Santos Paula , Queiroz Fabiana
Published: January 2019

The residual biomass of coffee, obtained after the oil extraction from coffee beans, called coffee beans residual press cake, has been attracted interest as a source of compounds with antioxidant capacity. This study investigated the effects of ethanolic and methanol‐acetone extracts of green coffee beans (GCB) and its residual press cake (GCC) on the phenolic composition and antioxidant capacity. Antioxidant capacity was assayed through five different methods (total phenolic compounds, •DPPH, ABTS, FRAP and β‐carotene bleaching assay), and the phenolic profile of the samples through High Performance Liquid Cromatography. GCB and GCC enclosed chlorogenic (55.16 and 64.96 mg g−1, respectively) and caffeic (25.07 and 44.37 mg g−1, respectively) acids as the major components, and the cake presented higher antioxidant capacity than the actual green bean. Antioxidant capacity was higher for GCC extracted with methanol and acetone. This study on the evaluation of the effects of the type of solvent on the bioactive compounds from GCB and GCC showed that this by‐product can be a source of new value‐added products, such as phenolic antioxidant adjuncts for food or pharmaceutic processing.
Bringing firms on board. Inclusiveness of the dual apprenticeship systems in Germany, Switzerland and Denmark
Authors: Bonoli Giuliano , Wilson Anna
Published: January 2019

In dual vocational education and training (VET) systems, the state and employers collaborate in order to meet a country’s needs in terms of education for youth and professional skills for the labour market. These systems are considered as effective tools to lower youth unemployment. However, since firms in dual VET systems select the apprentices, not every candidate gets access to in‐firm training. Consequently, governments develop measures that try to make their dual VET systems more inclusive. We present a categorisation of the different measures used to enhance inclusiveness in three dual collective skill formation countries (Switzerland, Germany and Denmark). We show that inclusiveness measures exist in each of the three countries but are limited in the extent to which firms are expected to play an active role in them. We conclude that the types of measures adopted are related to political economy traditions and the country’s level of macro‐corporatism.
Exploring in Silence: Hearing and Deaf Infants Explore Objects Differently Before Cochlear Implantation
Authors: Fagan Mary K.
Published: January 2019

Infant development has rarely been informed by the behavior of infants with sensory differences despite increasing recognition that infant behavior itself creates sensory learning opportunities. The purpose of this study of object exploration was to compare the behavior of hearing and deaf infants, with and without cochlear implants, in order to identify the effects of profound sensorineural hearing loss on infant exploration before cochlear implantation, the behavioral effects of access to auditory feedback after cochlear implantation, and the sensory motivation for exploration behaviors performed by hearing infants as well. The results showed that 9‐month‐old deaf infants explored objects as often as hearing infants but they used systematically different approaches and less variation before compared to after cochlear implantation. Potential associations between these early experiences and later learning are discussed in the context of embodied developmental theory, comparative studies, and research with adults. The data call for increased recognition of the active sensorimotor nature of infant learning and future research that investigates differences in sensorimotor experience as potential mechanisms in later learning and sequential memory development.
‘You don't know what you don't know’: The essential role of management exposure, understanding and commitment in peer workforce development
Authors: Byrne Louise , Roennfeldt Helena , Wang Ying , O'Shea Peri
Published: January 2019

The peer workforce has increased significantly in recent years; however, structured development and support for the roles are lacking. This paper explores the role of executive and senior management understanding in the employment of peer roles. In‐depth, semi‐structured interviews and one focus group were conducted with 29 participants from a range of nongovernment and public mental health services within Queensland, Australia. Findings of this study suggest management exposure to and understanding of peer work are essential to the development of an effective peer workforce. Exposure and understanding of peer roles reportedly led to greater acceptance and commitment from management. This commitment inspired action in the form of; enhanced support including advocacy/championing, increased development of roles and influenced culture within the organization to be more accepting of peer work. There was a perception that developing an ‘accepting’ organizational culture supported the integrity and expansion of peer roles including designated ‘peer management’ positions. Development of peer management positions is suggested as an effective means of improving the impact of peer perspectives, advocating for peer work and providing ongoing and timely supervision. Recommendations include the need for training and information for management on the unique function, purpose and value of peer roles; and the development of networks, including mentoring opportunities, for organizations with limited experience to gain support and advice from those with greater experience developing peer roles.
Validation of a wrist‐type home nocturnal blood pressure monitor in the sitting and supine position according to the ANSI/AAMI/ISO81060‐2:2013 guidelines: Omron HEM‐9600T
Authors: Kuwabara Mitsuo , Harada Kanako , Hishiki Yukiko , Kario Kazuomi
Published: January 2019

The purpose of the present study was to evaluate the performance of the Omron HEM‐9600T, an automatic wrist‐type device for self BP measurement, in the sitting position with the wrist at heart level and supine position according to the ANSI/AAMI/ISO81060‐2:2013 guidelines. In the supine position, we evaluated the device under 3 different conditions: using the supine with sideways palm position, the supine with upwards palm position, and the supine with downwards palm position. After 106 subjects were screened and 21 subjects were excluded, the same 85 subjects (38 men [44.7%] and 47 women [55.3%]) were included in the analyses for each position. The average age of the subjects was 54.5 ± 12.2 years (mean ± SD). The mean wrist circumference was 17.0 ± 2.4 cm. The wrist size distribution fulfilled the requirements of the guidelines. The mean differences between reference BPs and HEM‐9600T readings were 1.0 ± 6.7/1.4 ± 5.7 mm Hg, 6.6 ± 7.2/5.5 ± 6.0 mm Hg, 4.8 ± 7.2/4.9 ± 5.8 mm Hg, and 2.1 ± 7.2/2.8 ± 6.8 mm Hg for SBP/DBP in the sitting position, supine with sideways palm position, supine with upwards palm position, and supine with downwards palm position, respectively. In conclusion, the Omron HEM‐9600T in the sitting position fulfilled the validation criteria of the ANSI/AAMI/ISO81060‐2:2013 guidelines. On the other hand, the accuracies of HEM‐9600T in the supine position differed depending on the positioning of the palm, with only the downwards palm‐position measurement fulfilling both validation criteria of the ANSI/AAMI/ISO81060‐2:2013 guidelines.
Oestrogen‐related receptor alpha mediates chemotherapy resistance of osteosarcoma cells via regulation of ABCB1
Authors: Chen Yantao , Zhang Kunshui , Li Yang , Guo Ruilian , Zhang Kelin , Zhong Guifang , He Qing
Published: January 2019

Chemotherapy resistance is one of the major challenges for the treatment of osteosarcoma (OS). The potential roles of oestrogenic signals in the chemoresistance of OS cells were investigated. As compare to the parental cells, the doxorubicin and cisplatin (CDDP) resistant OS cells had greater levels of oestrogen‐related receptors alpha (ERRα). Targeted inhibition of ERRα by its specific siRNAs or inverse agonist XCT‐790 can restore the sensitivity of OS resistant cells to chemotherapy. This might be due to that si‐ERRα can decrease the expression of P‐glycoprotein (P‐gp, encoded by ABCB1), one important ABC membrane transporter for drug efflux. XCT‐790 can decrease the transcription and mRNA stability of ABCB1, while had no effect on protein stability of P‐gp. ERRα can bind to the transcription factor of SP3 to increase the transcription of ABCB1. Furthermore, XCT‐790 treatment decreased the expression of miR‐9, which can bind to the 3′UTR of ABCB1 and trigger its decay. Collectively, we found that ERRα can regulate the chemoresistance of OS cells via regulating the transcription and mRNA stability of ABCB1. Targeted inhibition of ERRα might be a potential approach for OS therapy.
Alantolactone promotes ER stress‐mediated apoptosis by inhibition of TrxR1 in triple‐negative breast cancer cell lines and in a mouse model
Authors: Yin Changtian , Dai Xuanxuan , Huang Xiangjie , Zhu Wangyu , Chen Xi , Zhou Qiulin , Wang Canwei , Zhao Chengguang , Zou Peng , Liang Guang , Rajamanickam Vinothkumar , Wang Ouchen , Zhang Xiaohua , Cui Ri
Published: January 2019

Triple‐negative breast cancer (TNBC) is a subtype of breast cancer with poor clinical outcome and currently no effective targeted therapies are available. Alantolactone (ATL), a sesquiterpene lactone, has been shown to have potential anti‐tumour activity against various cancer cells. However, the underlying mechanism and therapeutic effect of ATL in the TNBC are largely unknown. In the present study, we found that ATL suppresses TNBC cell viability by reactive oxygen species (ROS) accumulation and subsequent ROS‐dependent endoplasmic reticulum (ER) stress both in vitro and in vivo. Thioredoxin reductase 1 (TrxR1) expression and activity of were significantly up‐regulated in the TNBC tissue specimens compare to the normal adjacent tissues. Further analyses showed that ATL inhibits the activity of TrxR1 both in vitro and in vivo in TNBC and knockdown of TrxR1 in TNBC cells sensitized ATL‐induced cell apoptosis and ROS increase. These results will provide pre‐clinical evidences that ATL could be a potential therapeutic agent against TNBC by promoting ROS‐ER stress‐mediated apoptosis through partly targeting TrxR1.
Efficacy of photoactivated curcumin to decontaminate food surfaces under blue light emitting diode
Authors: Aurum Fawzan Sigma , Nguyen Loc Thai
Published: January 2019

The efficacy of photoactivated curcumin in decontaminating food surfaces using a 465 nm light emitting diode (LED) light source was investigated. Under studied conditions, LED illumination alone had negligible antibacterial effects while photoactivated curcumin exhibited strong bactericidal activities against Escherichia coli. Minimum inhibitory concentration of photosensitized curcumin against E. coli on nutrient agar surface at a concentration of 1.5 × 105 cfu/cm2 was estimated to be 1.60 × 10−3 M, combined with irradiation of 27.2 J/cm2 at 465 nm. Bacterial inactivation kinetics could be described by a Weibull model (R2 = 0.979–0.999, RMSE = 0.019–0.229). When the treatment was applied on grape surface, the efficiency was lower as compared to that on the agar surface. Photoactivation enhanced quality retention of the samples during storage with significant preservation of vitamin C, color, texture, and reduction of weight losses.

Practical applications

The study provides an alternative method for food surface decontamination. Inactivation of pathogens and spoilage microorganism by combined visible LED light source and natural photosensitizers minimizes the adverse processing effects on organoleptic and physicochemical quality of the treated foods. The approach could be further optimized, scaled up, and applied in food industries.
Adverse drug event‐related hospitalisation in persons with neurodevelopmental disorders: a state‐wide retrospective cohort study
Authors: Zhou M. , Du W. , Salvador‐Carulla L. , Glasgow N.
Published: January 2019

Background

Little is known about the sociodemographic and clinical characteristics of adverse drug events (ADEs) in patients with neurodevelopmental disorders (NDD).

Objective

The objective of this study was to describe and compare the demographic details of people with and without NDD hospitalised due to ADEs.

Methods

The all‐inclusive New South Wales Admitted Patient Data Collection from 2001 to 2014 was employed to identify ADE‐related hospitalisations in patients with NDD using the International Classification of Diseases 10th revision Australian modification codes. We derived case sets specific to different clinical groups and patient characteristics and compared proportional differences between patients with and without intellectual disability using chi squared tests.

Results

A total of 2173 patients with NDD were admitted for acute care of ADEs, accounting for 0.7% of all ADE‐related hospitalisations. Hospitalised ADEs among patients with NDD increased by twofold over the 14‐year study period. Psychotropic medications and opioid analgesic medications were leading causes of ADE‐related hospitalisations in patients with NDD. Compared with their counterparts, patients with NDD were younger, experienced more socio‐economic disadvantage and less private insurance coverage, suffered with less severe but different co‐morbid clinical conditions and incurred more challenges in the acute hospital care setting.

Conclusion

Although the pattern of ADE‐related hospitalisations in patients with NDD differed from that in patients without NDD, there is a lack of targeted healthcare programmes to meet their special needs. This study suggests the need for countermeasures in primary healthcare settings to reduce the burden of ADEs in this vulnerable group.
Alimentary Dignity: Defining a Decent Meal in Post‐Soviet Cuban Household Cooking
Authors: Garth Hanna
Published: January 2019

A medida que el sistema alimentario cubano contemporáneo cambia, los consumidores domésticos necesitan ajustar sus hábitos diarios de consumo alimentario. En este artículo demuestro las maneras en que los consumidores cubanos usan la categoría de la “comida decente” para mantener los límites de los alimentos “reales”. Introduzco la “dignidad alimentaria” como una estructura para entender por qué los cubanos consideran ciertas prácticas de consumo decentes, llamando a otros “no reales”. La noción de dignidad alimentaria es una forma de dar un significado social a nuevas formas de consumo mientras la disponibilidad de los alimentos cambia con cambios socioeconómicos en Cuba. La categorización de sus comidas en esta manera es una forma de afecto mediado que esta profundamente enredado con deseos de vivir de manera idealizada. Los conceptos de dignidad alimentaria y la comida decente contribuyen a una comprensión más amplia de cómo las personas hacen el significado de las circunstancias cambiantes de la vida. [comida, Cuba, globalizacion, identidad, mercados, nutricion]
Psychiatric Disorders After Attention‐Deficit/Hyperactivity Disorder: A Nationwide Population‐Based Study in Taiwan
Authors: Huang Ya‐Fang , Chiou Hung‐Yi , Chung Chi‐Hsiang , Chien Wu‐Chien , Chang Hsiu‐Ju
Published: January 2019

Purpose

To investigate the risk for psychiatric disorders in patients newly diagnosed with attention deficit hyperactive disorder (ADHD) from two longitudinal groups of children with and without ADHD.

Study Design

In total, 1,745 children newly diagnosed with ADHD and 6,980 participants without ADHD were identified from Taiwan's National Health Insurance Research Database in 2005 and followed until 2010. Risks for psychiatric disorders in the ADHD and non‐ADHD groups were compared.

Results

The ADHD group was 3.82 times more likely to develop psychiatric disorders than their counterparts. The ADHD group showed the highest risk for oppositional defiant disorder, followed by adult ADHD and autism spectrum disorder. Moreover, the time effects of psychiatric disorders in the ADHD group were significant. Patients with ADHD subtypes had a significant risk for psychiatric disorders compared to their counterparts.

Conclusions

A high risk for psychiatric disorders was revealed in this study among children with ADHD. Childhood ADHD, the duration after the ADHD diagnosis, and the ADHD subtype were associated with psychiatric disorders.

Clinical Relevance

Various psychiatric disorders were observed in children after they had been newly diagnosed with ADHD, indicating a need for integrated care that includes medical practitioners, family members, social workers, and early intervention workers for patients newly diagnosed with ADHD to decrease the risk for comprehensive psychiatric disorders.
Space that Transcends Time: Narrating the past in the Steilneset Memorial in VardØ
Authors: Tanović Sabina
Published: January 2019

This visual essay investigates the Steilneset Memorial (2011) in Vardø, Norway—a collaborative effort between the artist Louise Bourgeois and the architect Peter Zumthor. Consisting of two separate buildings, often referred to as a “line and a dot,” the project aims to narrate a centuries–old tragic history of witchcraft. The memorial was imagined as a commemorative project that responds to the spatial and cultural context of the location while also evoking the traumatic legacy. To address the centuries–old harrowing episode, the designers explored a concept of spirituality as a way to transcend historical time.
Considering Carnegie's Legacy in the Time of Trump: A Science and Policy Agenda for Studying Social Class
Authors: Williams Wendy R.
Published: January 2019

As one of the richest men in the world at a time of vast economic inequality, Andrew Carnegie published “The Gospel of Wealth” in 1889. In it, he delineated how wealth should be redistributed from the hands of the few to the many. Given SPSSI's 2018 conference location in Pittsburgh, and a similar concentration of wealth among a small group of White men today, it is an opportune time to consider the legacy of one of Pittsburgh's most famous citizens. Specifically, the comparison (and contrast) between Carnegie and President Trump provides an interesting backdrop for examining our present historical moment. Specifically, over the last 20 years, there has been renewed interest in studying social class among psychological researchers. Continuing with the conference theme of “building bridges,” this article will review the status of our knowledge about social class in order to provide a science and policy agenda for addressing poverty, wealth, and inequality in our time.