bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost analysis of ureteroscopy (URS) vs extracorporeal shockwave lithotripsy (ESWL) in the management of ureteric stones <10 mm in adults: a UK perspective
Authors: Constanti Margaret , Calvert Robert C. , Thomas Kay , Dickinson Andrew , Carlisle Sophie
Published: October 2019

Objectives

To compare the total cost of a treatment strategy starting with ureteroscopy (URS) vs a strategy starting with extracorporeal shockwave lithotripsy (ESWL).

Methods

For ureteric stones of <10 mm, URS or ESWL are the main treatment options that are considered. Although the interventions differ, the goal of the interventions is to achieve a stone‐free status. A systematic review and meta‐analysis undertaken as part of the National Institute for Health and Care Excellence (NICE) guideline on ‘Renal and ureteric stones: assessment and management’ identified URS as more effective, in terms of getting people stone free, but has a higher probability of re‐admission and adverse events (AEs) that contributes to downstream resource use. ESWL is initially less costly, but lower effectiveness means a greater need for repeat or ancillary procedures in order to get a patient stone free. Given these trade‐offs between benefits and costs, a cost analysis of URS and ESWL was undertaken as part of the NICE guideline, using evidence from the literature of effectiveness, re‐admission and AEs. The NICE guideline meta‐analysis showed a lot of heterogeneity and differences in how outcomes were reported between studies. The costing analysis, therefore only used studies where: (i) patients were rendered stone free, and (ii) where effectiveness, was based on the first‐line (initial) procedures. Exploratory quality adjusted life year (QALY) work was also undertaken to identify the QALY and quality of life (QoL) differences required for the most expensive intervention to be cost effective, based on the assumption that the difference in effectiveness between the initial procedures would be the main source of the QALY gain between the two strategies.

Results

The URS strategy was more costly overall than the ESWL strategy (incremental cost of £2387 [pounds sterling]). Sensitivity analysis varying the initial effectiveness of ESWL treatment (between the base case value of 82% and 40%) showed that URS would still be a more costly strategy even if the initial session of ESWL only had a success probability of 40%. A two‐way sensitivity analysis as part of the exploratory QALY work showed that ESWL would have to have very low effectiveness and people would have to wait for further treatment for many weeks (following a failed ESWL treatment) for there to be feasible QoL gains to justify the additional cost of the URS strategy.

Conclusions

ESWL is less effective at initial stone clearance and therefore requires more ancillary interventions than URS. However, the magnitude of the difference in costs means URS is unlikely to be cost effective intervention at a population level for first‐line treatment, implying ESWL should be the first choice treatment.
The Effects of Enrolling in Oversubscribed Prekindergarten Programs Through Third Grade
Authors: Weiland Christina , Unterman Rebecca , Shapiro Anna , Staszak Sara , Rochester Shana , Martin Eleanor
Published: October 2019

This study leverages naturally occurring lotteries for oversubscribed Boston Public Schools prekindergarten program sites between 2007 and 2011, for 3,182 children (M = 4.5 years old) to estimate the impacts of winning a first choice lottery and enrolling in Boston prekindergarten versus losing a first choice lottery and not enrolling on children’s enrollment and persistence in district schools, grade retention, special education placement, and third‐grade test scores. There are large effects on enrollment and persistence, but no effects on other examined outcomes for this subsample. Importantly, children who competed for oversubscribed seats were not representative of all appliers and almost all control‐group children attended center‐based preschool. Findings contribute to the larger evidence base and raise important considerations for future prekindergarten lottery‐based studies.
Pre‐clinical evidences for the efficacy of tryptanthrin as a potent suppressor of skin cancer
Authors: Shankar G. Mohan , Alex Vijai V. , Nisthul A. Amrutha , Bava Smitha V. , Sundaram Sankar , Retnakumari Archana P. , Chittalakkottu Sadasivan , Anto Ruby John
Published: October 2019

Objective

Clinical trials have demonstrated the efficacy of indigo naturalis, a traditional Chinese medicine ingredient, against psoriasis, a skin disease characterized by keratinocyte hyperproliferation and inflammation. The present study investigates the efficacy of tryptanthrin, a bioactive compound in indigo naturalis, against non‐melanoma skin cancer (NMSC) and the signalling events involved.

Methods

Efficacy of tryptanthrin against NMSC was assessed using DMBA/PMA‐induced skin carcinogenesis model in Swiss albino mice. Immunostaining for PCNA and ki‐67 was used to mark proliferating cells in tissues. Haematoxylin and eosin staining and toluidine staining were employed to assess inflammation, and TUNEL assay was used to detect apoptosis in tissues. The signalling events were evaluated using Western blot, imunohistochemistry and immunofluorescence staining. MTT assay and clonogenic assay were performed to assess the viability and proliferation of cancer cells, in vitro.

Results

In mice, topical application of tryptanthrin suppressed skin carcinogenesis. It attenuated inflammation, impeded the proliferation of hair follicle (HF) cells and suppressed the activation of β‐catenin, a major driver of HF cell proliferation. Additionally tryptanthrin suppressed the activation of ERK1/2 and p38, both of which promote β‐catenin activation and lowered the expression of c‐Myc and cyclin‐D1. Tryptanthrin suppressed the proliferation of the human NMSC cell line, A431 and abrogated EGF‐induced activation of β‐catenin and subsequent cytoskeletal rearrangement.

Conclusion

The study demonstrates with molecular evidence that tryptanthrin is an effective suppressor of NMSC.
Standardized measures of frailty predict hospital length of stay following orthotopic liver transplantation for hepatocellular carcinoma
Authors: DeMaria Samuel , Khromava Maryna , Schiano Thomas D. , Lin Hung‐Mo , Kim Sang
Published: October 2019

Frailty in liver transplant (LT) waitlisted patients has been shown to predict waitlist mortality. While not currently used to allocate organs, the relationship between preoperative frailty and postoperative outcomes following orthotopic LT needs further elucidation. We determined the frailty status of 50 OLT candidates listed for hepatocellular carcinoma (HCC) and examined relationships between frailty and outcomes on the waitlist and, if transplanted, 30‐day mortality, hospital length of stay (LOS), ICU LOS, and several other secondary outcomes. The overall prevalence of frailty was 30%, and the median natural MELD score for patients was 13. The overall hospital LOS for the frail group was longer (14.5 days [IQR 12‐19]) as compared to the non‐frail group (8 days [IQR 7‐13]); P = .015. Groups also differed in the time to their first PT session (6 days [IQR 4‐15] for the frail vs 4 days [IQR 3‐7] for the non‐frail patients; P = .042). There was no statistically significant difference in other outcomes measures, including ICU LOS and 30‐day mortality. Frailty in OLT patients with diagnosed HCC is a predictor of longer hospital stay and longer time to the first completed PT session independent of preoperative MELD scores.
Association of diagnosed obstructive sleep apnea with kidney transplant outcomes
Authors: Tiwari Rachna , Lyu Beini , Alagusundaramoorthy Sayee , Astor Brad C. , Mandelbrot Didier A. , Parajuli Sandesh
Published: October 2019

Obstructive sleep apnea (OSA) is common but underdiagnosed among patients with kidney disease. This study examines whether the diagnosis of OSA in kidney transplant recipients (KTR) affected death, death‐censored graft failure (DCGF), and acute rejection (AR). We analyzed the records of KTR who underwent transplant between 2000 and 2015. A total of 4014 kidney transplants were performed during the study period. Of these, 415 (10.3%) had a diagnosis of pretransplant OSA. Pretransplant OSA was associated with a higher risk of death in unadjusted analyses. After adjustment for potential confounders, pretransplant OSA was not associated with risk of death (HR = 1.04, 95% CI: 0.80‐1.36). Similarly, pretransplant OSA was associated with a slightly higher incidence of DCGF or AR but neither associations were significant (HR: 1.23, 95% CI: 0.85‐1.47 for DCGF; HR 1.10, 95% CI: 0.90‐1.36 for AR). A total of 117 (3.3%) were diagnosed with de novo OSA after transplant. Similar to the pretransplant OSA, unadjusted HR for death was significantly higher in the de novo OSA group (HR: 1.48, 95% CI: 1.19‐1.84); however, after adjustment, de novo OSA was not significantly associated with risk of death (HR: 1.15, 95% CI: 0.92‐1.45). Similarly, DCGF and AR rates were not significantly associated with de novo OSA (HR: 1.10, 95% CI: 0.84‐1.44 for DCGF; HR 1.10, 95% CI: 0.90‐1.33 for AR). Our work did not detect significant associations between OSA and risk of death, graft failure, and rejection but the estimates might be underestimated due to underdiagnosis of OSA.
Population Pharmacokinetic/Pharmacodynamic Analysis of Intravenous Zanamivir in Healthy Adults and Hospitalized Adult and Pediatric Subjects With Influenza
Authors: Zuo Peiying , Collins Jon , Okour Malek , Barth Aline , Shortino Denise , Yates Phillip , Roberts Grace , Watson Helen A. , Peppercorn Amanda , Hossain Mohammad
Published: October 2019

Zanamivir is a potent and highly selective inhibitor of influenza neuraminidase in which the inhibition of this enzyme prevents the virus from infecting other cells and specifically prevents release of the new virion from the host cell membrane. It is available as an oral powder for inhalation and intravenous formulations. The current population pharmacokinetic model based on data from eight studies of subjects treated with the intravenous formulation (125 healthy adults and 533 hospitalized adult and pediatric subjects with suspected or confirmed influenza) suggested a decreased zanamivir clearance in pediatric and renal impairment adult subjects. It also indicates that b.i.d. dosing is necessary to keep the exposure in influenza infected subjects above the 90% inhibitory concentration values of recently circulating viruses over the dosing interval. In the exposure‐response analysis (phases II and III studies), no apparent relationship was found between zanamivir exposure and clinically relevant pharmacodynamic end points.
A Double‐Blind, Phase I, Single Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of BOS161721 in Healthy Subjects
Authors: Hussaini Azra , Mukherjee Rajat , Berdieva Dina M. , Glogowski Christen , Mountfield Richard , Ho Peter T.C.
Published: October 2019

The purpose of this study was to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of BOS161721, a humanized immunoglobulin G1 triple mutation (M252Y/S254T/T256E) monoclonal antibody that inhibits interleukin‐21 (IL‐21) bioactivity. This randomized, single‐center, double‐blind, placebo‐controlled study randomized healthy volunteers 3:1 to single ascending intravenous and subcutaneous doses of BOS161721 (range 1–240 mg) or placebo. BOS161721 and placebo groups had similar rates of adverse events, mostly mild; none led to study discontinuation. There were no clinically significant findings in physical examination, vital signs, or laboratory assessment. In the pooled BOS161721 population, four subjects (8.5%) tested antidrug antibody‐positive predose, and seven (14.9%) postdose. Absolute CD4+ lymphocyte count remained normal throughout follow‐up. BOS161721 administered subcutaneously was absorbed slowly, with a median time to maximum concentration (Tmax) of 144 hours across doses (range 1–15 days) and a mean apparent terminal elimination half‐life of 80–87 days for doses ≥ 30 mg. Area under the concentration‐time curve from time zero to infinity (AUC0‐inf) and maximum observed concentration (Cmax) were linear across doses > 10 mg. Subcutaneous bioavailability was 64%. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3) decreased dose‐dependently with threshold characteristics at doses of ≥ 10 mg. Downregulation in BATF, IL6, LAG3, and SOCS3 genes caused by IL‐21 stimulation was reversed dose‐dependently. BOS161721 was well‐tolerated across doses, suppressed IL‐21‐induced pSTAT3 dose‐dependently, and reversed downregulation of genes critical to tolerance induction and T‐cell exhaustion induced by IL‐21. Further clinical studies are ongoing in patients with systemic lupus erythematosus, in which IL‐21 has a pathogenetic role.
Itraconazole Increases Ibrutinib Exposure 10‐Fold and Reduces Interindividual Variation—A Potentially Beneficial Drug‐Drug Interaction
Authors: Tapaninen Tuija , Olkkola Aleksi M. , Tornio Aleksi , Neuvonen Mikko , Elonen Erkki , Neuvonen Pertti J. , Niemi Mikko , Backman Janne T.
Published: October 2019

The oral bioavailability of ibrutinib is low and variable, mainly due to extensive first‐pass metabolism by cytochrome P450 (CYP) 3A4. The unpredictable exposure can compromise its safe and effective dosing. We examined the impact of itraconazole on ibrutinib pharmacokinetics. In a randomized crossover study, 11 healthy subjects were administered itraconazole 200 mg or placebo twice on day 1, and once on days 2–4. On day 3, 1 hour after itraconazole (placebo) and breakfast, ibrutinib (140 mg during placebo; 15 mg during itraconazole) was administered. Itraconazole increased the dose‐adjusted geometric mean area under the concentration‐time curve from zero to infinity (AUC0–∞) of ibrutinib 10.0‐fold (90% confidence interval (CI) 7.2–13.9; P < 0.001) and peak plasma concentration (Cmax) 8.8‐fold (90% CI 6.3–12.1; P < 0.001). During itraconazole, the intersubject variation for the AUC0–∞ (55%) and Cmax (53%) was around half of that during placebo (104%; 99%). In conclusion, itraconazole markedly increases ibrutinib bioavailability and decreases its interindividual variability, offering a possibility to improved dosing accuracy and cost savings.
Natural compulsive‐like behaviour in the deer mouse (Peromyscus maniculatus bairdii) is associated with altered gut microbiota composition
Authors: Scheepers Isabella M. , Cryan John F. , Bastiaanssen Thomaz F. S. , Rea Kieran , Clarke Gerard , Jaspan Heather B. , Harvey Brian H. , Hemmings Sian M. J. , Santana Leonard , van der Sluis Rencia , Malan‐Müller Stefanie , Wolmarans De Wet
Published: October 2019

Obsessive–compulsive disorder (OCD) is a psychiatric illness that significantly impacts affected patients and available treatments yield suboptimal therapeutic response. Recently, the role of the gut–brain axis (GBA) in psychiatric illness has emerged as a potential target for therapeutic exploration. However, studies concerning the role of the GBA in OCD are limited. To investigate whether a naturally occurring obsessive–compulsive‐like phenotype in a rodent model, that is large nest building in deer mice, is associated with perturbations in the gut microbiome, we investigated and characterised the gut microbiota in specific‐pathogen‐free bred and housed large (LNB) and normal (NNB) nest‐building deer mice of both sexes (n = 11 per group, including three males and eight females). Following baseline characterisation of nest‐building behaviour, a single faecal sample was collected from each animal and the gut microbiota analysed. Our results reveal the overall microbial composition of LNB animals to be distinctly different compared to controls (PERMANOVA p < .05). While no genera were found to be significantly differentially abundant after correcting for multiple comparisons, the normal phenotype showed a higher loading of Prevotella and Anaeroplasma, while the OC phenotype demonstrated a higher loading of Desulfovermiculus, Aestuariispira, Peptococcus and Holdemanella (cut‐off threshold for loading at 0.2 in either the first or second component of the PCA). These findings not only provide proof‐of‐concept for continued investigation of the GBA in OCD, but also highlight a potential underlying aetiological association between alterations in the gut microbiota and the natural development of obsessive–compulsive‐like behaviours.
Exploring the Role of Practical Wisdom in Addressing Adolescent Childrearing Dilemmas
Authors: Small Stephen A. , Metler David Charles
Published: October 2019

Objective

To explore whether practical wisdom may provide a useful lens for understanding how mothers can address difficult childrearing problems more effectively when raising adolescents.

Background

One of the major difficulties of raising adolescents is that there are no clear‐cut responses or universal solutions to many of the problems that regularly arise. Parents are expected to make responsible decisions about complex, indefinite problems even though they may lack a thorough understanding of the situation and have little formal training in childrearing. Practical wisdom—the ability to make sound, ethical judgments and decisions about difficult and uncertain problems—may be a valuable asset for addressing such challenges.

Method

Thirty mothers of adolescents (12–17 years of age) were asked to reason aloud about how they would respond to a series of hypothetical childrearing dilemmas.

Results

Guided by prior work on practical wisdom, our qualitative analysis identified a complex combination of eight interrelated parenting wisdom strategies: Compassion for Self and Child, Integrative Thinking, Parenting Knowledge, Perspective‐Taking, Problem‐Framing, Purpose Identification, Reflection, and Socioemotional Awareness.

Conclusion

The findings provide evidence that mothers sometimes use a process that has been historically conceptualized as practical wisdom and offer insight into what some of these practices entail.

Implications

The identification of these wise problem‐solving strategies highlight an important overlooked aspect of childrearing and hold promise as a valuable asset for helping mothers address difficult parenting problems.
Bovine milk transcriptome analysis reveals microRNAs and RNU2 involved in mastitis
Authors: Lai Yu‐Chang , Lai Yu‐Ting , Rahman Md Mahfuzur , Chen Hui‐Wen , Husna Al Asmaul , Fujikawa Takuro , Ando Takaaki , Kitahara Go , Koiwa Masateru , Kubota Chikara , Miura Naoki
Published: October 2019

Mastitis is a common inflammatory infectious disease in dairy cows. To understand the microRNA (miRNA) expression profile changes during bovine mastitis, we undertook a genome‐wide miRNA study of normal milk and milk that tested positive on the California mastitis test for bovine mastitis (CMT+). Twenty‐five miRNAs were differentially expressed (23 miRNAs upregulated and two downregulated) during bovine mastitis relative to their expression in normal milk. Upregulated mature miR‐1246 probably derived from a U2 small nuclear RNA rather than an miR‐1246 precursor. The significantly upregulated miRNA precursors and RNU2 were significantly enriched on bovine chromosome 19, which is homologous to human chromosome 17. A gene ontology analysis of the putative mRNA targets of the significantly upregulated miRNAs showed that these miRNAs were involved in binding target mRNA transcripts and regulating target gene expression, and a Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the upregulated miRNAs were predominantly related to cancer and immune system pathways. Three novel miRNAs were associated with bovine mastitis and were relatively highly expressed in milk. We confirmed that one of the novel mastitis‐related miRNAs was significantly upregulated using a digital PCR system. The differentially expressed miRNAs were involved in human cancers, infections, and immune‐related diseases. The genome‐wide analysis of miRNA profiles in this study provides insight into bovine mastitis and inflammatory diseases.

Databases

The miRNAseq generated for this study can be found in the Sequence Read Archive (SRA) under BioProject Number PRJNA421075 and SRA Study Number SRP126134 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA421075).
Effects of two centuries of global environmental variation on phenology and physiology of Arabidopsis thaliana
Authors: DeLeo Victoria L. , Menge Duncan N. L. , Hanks Ephraim M. , Juenger Thomas E. , Lasky Jesse R.
Published: October 2019

Intraspecific trait variation is caused by genetic and plastic responses to environment. This intraspecific diversity is captured in immense natural history collections, giving us a window into trait variation across continents and through centuries of environmental shifts. Here we tested if hypotheses based on life history and the leaf economics spectrum explain intraspecific trait changes across global spatiotemporal environmental gradients. We measured phenotypes on a 216‐year time series of Arabidopsis thaliana accessions from across its native range and applied spatially varying coefficient models to quantify region‐specific trends in trait coordination and trait responses to climate gradients. All traits exhibited significant change across space or through time. For example, δ15N decreased over time across much of the range and leaf C:N increased, consistent with predictions based on anthropogenic changes in land use and atmosphere. Plants were collected later in the growing season in more recent years in many regions, possibly because populations shifted toward more spring germination and summer flowering as opposed to fall germination and spring flowering. When climate variables were considered, collection dates were earlier in warmer years, while summer rainfall had opposing associations with collection date depending on regions. There was only a modest correlation among traits, indicating a lack of a single life history/physiology axis. Nevertheless, leaf C:N was low for summer‐ versus spring‐collected plants, consistent with a life history–physiology axis from slow‐growing winter annuals to fast‐growing spring/summer annuals. Regional heterogeneity in phenotype trends indicates complex responses to spatiotemporal environmental gradients potentially due to geographic genetic variation and climate interactions with other aspects of environment. Our study demonstrates how natural history collections can be used to broadly characterize trait responses to environment, revealing heterogeneity in response to anthropogenic change.
Global change biology: A primer
Authors: Sage Rowan F.
Published: October 2019

Because of human action, the Earth has entered an era where profound changes in the global environment are creating novel conditions that will be discernable far into the future. One consequence may be a large reduction of the Earth's biodiversity, potentially representing a sixth mass extinction. With effective stewardship, the global change drivers that threaten the Earth's biota could be alleviated, but this requires clear understanding of the drivers, their interactions, and how they impact ecological communities. This review identifies 10 anthropogenic global change drivers and discusses how six of the drivers (atmospheric CO2 enrichment, climate change, land transformation, species exploitation, exotic species invasions, eutrophication) impact Earth's biodiversity. Driver impacts on a particular species could be positive or negative. In either case, they initiate secondary responses that cascade along ecological lines of connection and in doing so magnify the initial impact. The unique nature of the threat to the Earth's biodiversity is not simply due to the magnitude of each driver, but due to the speed of change, the novelty of the drivers, and their interactions. Emphasizing one driver, notably climate change, is problematic because the other global change drivers also degrade biodiversity and together threaten the stability of the biosphere. As the main academic journal addressing global change effects on living systems, GCB is well positioned to provide leadership in solving the global change challenge. If humanity cannot meet the challenge, then GCB is positioned to serve as a leading chronicle of the sixth mass extinction to occur on planet Earth.
A meta‐analysis examining lactic acid bacteria inoculants for maize silage: Effects on fermentation, aerobic stability, nutritive value and livestock production
Authors: Bernardi Alexandre , Härter Carla J. , Silva Antonio W. L. , Reis Ricardo A. , Rabelo Carlos H. S.
Published: October 2019

A database containing 140 articles published in journals (731 treatment means evaluated) was used to examine the effect of different lactic acid bacteria (LAB) on fermentation, chemical composition and aerobic stability of maize (corn) silage. Compared with the control, dry matter (DM) loss increased by 8% and 50% (p < .01) due to inoculation of maize silage with either homolactic LAB (hoLAB) or heterolactic LAB (heLAB). In vitro DM digestibility of maize silage increased only with hoLAB inoculation (+2.22%; p < .01). The heLAB inoculation increased (p < .01) the aerobic stability of maize silage by 71.3 hr. To investigate the effect of silage inoculation on livestock production, a second database comprising 35 articles [99 treatment means evaluated based on results from 648 cattle (429 beef cattle and 219 dairy cows) and 298 sheep] was used. Inoculation of maize silage with either hoLAB or heLAB did not affect milk yield (p > .05), but their combination (mixLAB) depressed milk yield (–2.5 kg/day; p < .01). Inoculation with hoLAB increased DM intake in sheep (+0.15 kg/day; p = .02), but decreased it in beef cattle (–0.26 kg/day; p = .01) without affecting average daily gain for both sheep and beef cattle (p ≥ .06). In conclusion, fermentative loss increased regardless of the bacterial inoculant used, while aerobic stability increased mainly by using heLAB. Benefits from hoLAB inoculation on animal performance were noted only for feed intake in sheep, while productive performances of dairy cows and beef cattle were not improved.
IL‐17 and its role in inflammatory, autoimmune, and oncological skin diseases: state of art
Authors: Bernardini Nicoletta , Skroza Nevena , Tolino Ersilia , Mambrin Alessandra , Anzalone Alessia , Balduzzi Veronica , Colapietra Daniela , Marchesiello Anna , Michelini Simone , Proietti Ilaria , Potenza Concetta
Published: October 2019

Recent data support the theory of the involvement of IL‐17 in the pathogenesis of several chronic inflammatory skin diseases (psoriasis, atopic dermatitis, acne, hidradenitis suppurativa) and autoimmune skin diseases (alopecia areata, vitiligo, bullous diseases). Even if the role of IL‐17 in inflammatory and autoimmune diseases has been reported extensively, its role in tumor is still controversial. Some reports show that Th17 cells eradicate tumors, while others reveal that they promote the initiation and early growth of tumors. Herein, we review the role of IL‐17 in the involvement of some common dermatologic diseases: psoriasis, atopic dermatitis, hidradenitis suppurativa, acne, vitiligo, melanoma, and nonmelanoma skin cancers.
Polycystic ovary syndrome in adolescent girls
Authors: Ibáñez Lourdes , de Zegher Francis
Published: October 2019

PCOS is already a prevalent endocrinopathy in adolescent girls, and its prevalence is rising further since, in essence, it is the result of a mismatch between an energy‐sparing (epi)genetic background and a (relatively) obesogenic environment. This mismatch results in an excess of fat storage in ectopic depots, notably in the liver and viscera (= hepato‐visceral, or central fat). There is still no FDA‐approved treatment for adolescent PCOS. The prime aim should be a preferential loss of central fat, through lifestyle measures. Failure to sustain these measures is frequent, and the standard approach is to add an estroprogestagen contraceptive, even for girls who do not need contraception. Treatment with SPIOMET, a low‐dose combination of spironolactone (to antagonize androgen and mineralocorticoid effects, and to activate BAT thereby raising energy expenditure), pioglitazone (to raise circulating HMW adiponectin concentrations) and metformin, is an alternative approach that holds the potential to revert the PCOS phenotype.
Using a collaborative decision-making approach to identify, prioritise and respond to issues influencing Good Pharmacy Practice across countries of the Western Pacific Region
Authors: Jackson John , Caliph Suzanne , Chui Wai Keung , Ocampo Leonila
Published: October 2019

Objectives

The Western Pacific Pharmaceutical Forum aims to foster Good Pharmacy Practice (GPP) in the Western Pacific Region (WPR). Our objective in this work was to develop and implement a process that equitably and constructively engaged pharmacy associations from the diverse cultures, languages and models of pharmacy practice in the WPR to identify common issues influencing the implementation of GPP.

Methods

The World Café concept was incorporated into a modified Tuckman's model for group development to conduct a workshop of leaders from the major pharmacy associations of the WPR. Facilitated discussion groups and collaborative decision-making were used to gather opinions and achieve agreement between the regional leaders.

Key findings

Participants reported the method to be open, systematic and enabled full contribution. Two major issues were identified in relation to each of the four key pharmacist roles associated with GPP. The regional pharmacy leaders agreed the common priority issue for implementing GPP as: ‘National competency standards should be established to enable the formulation of professional development framework that lead to enhanced pharmacy practice and patient care’ and developed a strategy and work plan to address this issue.

Conclusions

Identification of GPP issues and the common major priority occurred with shared knowledge of the current state of practice across the WPR. The adopted methodology overcame cultural and practice differences to ensure full and equal participation of all delegates. The approach ensured ownership by all participants of the strategy and work plan developed to address competency and professional development in the WPR.
Travail et normes comptables internationales: une question de justice sociale
Authors: JUBÉ Samuel
Published: October 2019

En tant que garante internationale de la justice sociale, l'OIT se trouve confrontée à une révolution comptable mondiale, parachevée par les normes comptables internationales (IAS‐IFRS). La comptabilité mesurait autrefois l'économie en rapport avec les capacités et les responsabilités des travailleurs et de ceux qui en disposent. C'est aujourd'hui l'exact opposé: les normes IAS‐IFRS ont perdu le sens de la mesure du travail et de l'entreprise en se référant au concept abstrait d'une entité cybernétique capable d'incessantes réorganisations, au prix d'inégalités sans limites. L'auteur en dénonce les incohérences et démontre la nécessité de redonner au travail toute sa valeur comptable.
Highly oxidized low‐density lipoprotein mediates activation of monocytes but does not confer interleukin‐1β secretion nor interleukin‐15 transpresentation function
Authors: Sieg Scott F. , Bazdar Douglas A. , Zidar David , Freeman Michael , Lederman Michael M. , Funderburg Nicholas T.
Published: October 2019

Oxidized low‐density lipoprotein (LDL) contributes to cardiovascular disease in part by mediating activation and maturation of monocytes and macrophages. Furthermore, co‐localization studies using histochemical approaches have implicated a potential role for oxidized LDL as a mediator of interleukin‐15 (IL‐15) expression in myeloid cells of atherosclerotic plaque. The latter activity could be an important pro‐inflammatory mechanism that mediates myeloid cell/T‐cell crosstalk. Here, we examined the responses of primary human monocytes to highly oxidized LDL molecules. Oxidized LDL readily induced secretion of chemokines MCP‐1 (CCL2) and GRO‐α (CXCL1) but unlike lipopolysaccharide (LPS), has limited capacity to induce a variety of other cytokines including tumor necrosis factor‐α, IL‐6, IL‐1β and interferon‐γ‐induced protein‐10 and also displayed a poor capacity to induce p‐Akt or P‐S6 signaling. Failure of oxidized LDL to induce IL‐1β secretion was associated with limited induction of caspase‐1 activation. Furthermore, despite finding evidence that oxidized LDL could enhance the expression of IL‐15 and IL‐15 receptor expression in monocytes, we found no evidence that it could confer IL‐15 transpresentation capability to these cells. This observation contrasted with induction of IL‐15 transpresentation in lipopolysaccharide‐stimulated monocytes. Overall, our data suggest that highly oxidized LDL is a selective inducer of monocyte activation. Sterile inflammatory mediators, particularly those implicated in Toll‐like receptor 4 signaling, may play a role in vascular pathology but the activities of these agents are not uniform.
Mental health nurses’ experience of physical health care and health promotion initiatives for people with severe mental illness
Authors: Lundström Sofie , Jormfeldt Henrika , Hedman Ahlström Britt , Skärsäter Ingela
Published: October 2019

Health care for people with severe mental illness is often divided into physical health care and mental health care despite the importance of a holistic approach to caring for the whole person. Mental health nurses have an important role not only in preventing ill health, but also in promoting health, to improve the overall health among people with severe mental illness and to develop a more person‐centred, integrated physical and mental health care. Thus, the aim of this study was to describe mental health nurses’ experiences of facilitating aspects that promote physical health and support a healthy lifestyle for people with severe mental illness. Interviews were conducted with mental health nurses (n = 15), and a qualitative content analysis was used to capture the nurse’s experiences. Analysis of the interviews generated three categories: (i) to have a health promotion focus in every encounter, (ii) to support with each person’s unique prerequisites in mind and (iii) to take responsibility for health promotion in every level of the organization. The results show the importance of a health promotion focus that permeates the entire organization of mental health care. Shared responsibility for health and health promotion activities should exist at all levels: in the person‐centred care in the relation with the patient, embedded in a joint vision within the working unit, and in decisions at management level.
Social media use and ethics violations: Nurses’ responses to hypothetical cases
Authors: Demiray A. , Çakar M. , Açil A. , Ilaslan N. , Savas Yucel T.
Published: October 2019

Aim

This study aimed to evaluate nurses’ ability to evaluate ethical violations to hypothetical case studies involving social media use.

Background

Inappropriate use of social media necessitates health institutes, academic institutes, nurses and educators to consider occupational ethical principles while creating a  policy and guide on the usage of social media.

Method

The data were collected confidentially from the nurses working at a university hospital in Turkey, using the Personal Information Form and the Ethic Case Form. The study was carried out using descriptive and inferential analysis.

Findings

Analysis of the data showed that the majority of the nurses had received training in ethics, used WhatsApp social media application most often, spent less than an hour a day on social media platforms and used social media to follow daily posts. Analyses of the ethical case evaluations showed that nurses’ level of education and ethics training status was influential on their Case 1 evaluations and the length of time they had worked was effective in Case 2 evaluations. When Case 3 evaluations of nurses were analysed according to ethics training, statistically significant differences were found. The analyses of the Case 4 and Case 5 evaluations showed that no statistically significant differences were found according to nurses’ descriptive characteristics.

Conclusion

The study determined that education level, ethical training status, the source of ethics training and the duration of their work in the profession were effective regarding the case evaluation of the nurses.

Implications for nursing and health policy

Nursing policymakers, educators, administrators and clinicians need to cooperate in the development of ethical awareness and creation of solutions to violations, the preparation of guidelines for social media use.
In vitro human cord blood platelet lysate characterisation with potential application in wound healing
Authors: Losi Paola , Barsotti Maria C. , Foffa Ilenia , Buscemi Marianna , De Almeida Carolina V. , Fabbri Marco , Gabbriellini Sabrina , Nocchi Francesca , Ursino Silvia , Urciuoli Patrizia , Mazzoni Alessandro , Soldani Giorgio
Published: October 2019

Platelets contain abundant growth factors and cytokines that have a positive influence on the migration and proliferation of different cell types by modulating its physiopathological processes. As it is known that human umbilical cord blood platelet lysate (UCB‐PL) contains a supraphysiological concentration of growth factors, in the present study, we investigated its effectiveness in wound‐healing processes. Human UCB‐PL was obtained by the freeze/thaw of platelet concentrate (1.1 × 109 platelets/L), and its effect was evaluated on human or mouse endothelial cells, monocytes, fibroblasts, and keratinocytes in different concentrations. Human UCB‐PL was observed to have high levels of pro‐angiogenic growth factor than peripheral blood platelet‐rich plasma. Among the cell lines, different concentrations of human UCB‐PL were necessary to influence their viability and proliferation. For L929 cells, 5% of total volume was necessary, while for human umbilical vein endothelial cell, it was 10%. Cell migration on monocytes was increased with respect to the positive control, and scratch closure on keratinocytes was increased with respect to serum‐free medium with only 10% of human UCB‐PL. We concluded that the human UCB‐PL may be useful to produce a large amount of standard platelet concentrates sufficient for several clinical‐scale expansions avoiding inter‐individual variability, which can also be used as a functional tool for clinical regenerative application for wound healing.
High temperature creep‐mediated functionality in polycrystalline barium titanate
Authors: Ren Pengrong , Höfling Marion , Koruza Jurij , Lauterbach Stefan , Jiang Xijie , Frömling Till , Khatua Dipak Kumar , Dietz Christian , Porz Lukas , Ranjan Rajeev , Kleebe Hans‐Joachim , Rödel Jürgen
Published: October 2019

Dislocations in oxides can be described as charged line defects and means for one‐dimensional doping, which can tune electrical and thermal properties. Furthermore, theoretically it was shown that dislocations can pin ferroelectric domain walls. Broader application of this concept hinges on the development of a methodology to avail this approach to polycrystalline ceramics. To this end, we use different creep mechanisms as a method to introduce multidimensional defects and quantify structural changes. A deformation map for fine‐grained barium titanate is provided and the influences of the defects and creep regimes are correlated in this first study to modifications of electrical conductivity, dielectric, ferroelectric, and piezoelectric properties. A plastic deformation of 1.29% resulted in an increase in the Curie temperature by 5°C and a decrease in electromechanical strain by 30%, pointing toward electromechanical hardening by dislocations.
Size‐induced grain boundary energy increase may cause softening of nanocrystalline yttria‐stabilized zirconia
Authors: Bokov Arseniy , Rodrigues Neto Joao B. , Lin Feng , Castro Ricardo H. R.
Published: October 2019

An increase in hardness with reducing grain sizes is commonly observed in oxide ceramics in particular for grain sizes below 100 nm. The inverse behavior, meaning a decrease in hardness below a critically small grain size, may also exist consistently with observations in metal alloys, but the causing mechanisms in ceramics are still under debate. Here we report direct thermodynamic data on grain boundary energies as a function of grain size that suggest that the inverse relation is intimately related to a size‐induced increase in the excess energies. Microcalorimetry combined with nano and microstructural analyses reveal an increase in grain boundary excess energy in yttria‐stabilized zirconia (10YSZ) when grain sizes are below 36 nm. The onset of the energy increase coincides with the observed decrease in Vickers indentation hardness. Since grain boundary energy is an excess energy related to boundary strength/stability, the results suggest that softening is driven by the activation of grain boundary mediated processes facilitated by the relatively weakened boundaries at the ultra‐fine nanoscale which ultimately induce the formation of an energy dissipating subsurface crack network during indentation.
Blockholder leverage and payout policy: Evidence from French holding companies
Authors: Anantavrasilp Sereeparp , de Jong Abe , DeJong Douglas V. , Hege Ulrich
Published: October 2019

This paper focuses on dominant owners’ use of leverage to finance their blockholdings and its relationship to dividend policy. We postulate that blockholder leverage may impact payout policy, in particular when earnings are hit by a negative shock. We use panel data for France where blockholders have tax incentives to structure their leverage in pyramidal holding companies and study the effect of the financial crisis in 2008/2009. We find no difference in payout policy and financial behavior during the 1999 to 2008 period between firms with levered owners and other firms. However, in the years 2009 to 2011 following the crisis, dividend payouts increase in proportion to pyramidal debt of dominant owners. We inspect pyramidal entities individually and find that on average only 60% of dividends are passed through to the ultimate owners, with the rest predominantly used to meet debt service obligations of the pyramidal entities.
Recommendations for (Discontinuation of) Statin Treatment in Older Adults: Review of Guidelines
Authors: van der Ploeg Milly A. , Floriani Carmen , Achterberg Wilco P. , Bogaerts Jonathan M.K. , Gussekloo Jacobijn , Mooijaart Simon P. , Streit Sven , Poortvliet Rosalinde K.E. , Drewes Yvonne M.
Published: October 2019

OBJECTIVES

As a person's age increases and his/her health status declines, new challenges arise that may lead physicians to consider deprescribing statins. We aimed to provide insight into recommendations available in international cardiovascular disease prevention guidelines regarding discontinuation of statin treatment applicable to older adults.

DESIGN

We systematically searched PubMed, EMBASE, EMCARE, and the websites of guideline development organizations and online guideline repositories for cardiovascular disease prevention guidelines aimed at the general population. We selected all guidelines with recommendations (instructions and suggestions) on discontinuation of statin treatment applicable to older adults, published between January 2009 and April 2019. In addition, we performed a synthesis of information from all other recommendations for older adults regarding statin treatment. Methodological quality of the included guidelines was appraised using the appraisal of guidelines for research & evaluation II (AGREE II) instrument.

RESULTS

Eighteen international guidelines for cardiovascular disease prevention in the general adult population provided recommendations for statin discontinuation that were applicable to older adults. We identified three groups of instructions for statin discontinuation related to statin intolerance, and none was specifically aimed at older adults. Three guidelines also included suggestions to consider statin discontinuation in patients with poor health status. Of the 18 guidelines included, 16 made recommendations regarding statin treatment in older adults, although details on how to implement these recommendations in practice were not provided.

CONCLUSION

Current international cardiovascular disease prevention guidelines provide little specific guidance for physicians who are considering statin discontinuation in older adults in the context of declining health status and short life expectancy. J Am Geriatr Soc 68:417–425, 2020
Effect of Moringa oleifera supplementation on productive performance, colostrum composition and serum biochemical indexes of sow
Authors: Sun Jia‐Jie , Wang Peng , Chen Guo‐Ping , Luo Jun‐Yi , Xi Qian‐Yun , Cai Geng‐Yuan , Wu Jia‐Han , Zeng Bin , Xie Yue‐Qin , Jiang Qing‐Yan , Chen Ting , Zhang Yong‐Liang
Published: October 2019

Moringa oleifera has been considered as a potential functional feed or food, since it contains multiple components beneficial to animal and human. However, little is known about the effects of Moringa oleifera supplementation on productive performances in sows. In the current study, the results showed that dietary Moringa oleifera significantly decreased the farrowing length and the number of stillborn (p < .05), while had an increasing trend in the number of live‐born (0.05 < p < .10). Furthermore, 8% Moringa oleifera supplementation significantly elevated protein levels in the colostrum (p < .05); 4% Moringa oleifera lowed serum urea nitrogen of sows after 90 days of gestation (p < .05) and significantly decreased serum glucose on 10 days of lactation (p < .05). Both groups showed significant elevation in serum T‐AOC activity (p < .05). The serum malondialdehyde (MDA) of sows declined significantly in 4% Moringa oleifera addition group (p < .05). 8% Moringa oleifera meal significantly elevated serum CAT activity after 60 days of gestation (p < .05), while decreased the serum MDA level and increased the serum GSH‐Px activity of sows at 10 days of lactation (p < .05). Of piglets, both two dosages of Moringa oleifera supplementation essentially reduced the serum urea nitrogen (p < .05), and 4% Moringa oleifera meal increased serum total protein (p < .05). In addition, piglets that received 8% Moringa oleifera had the highest serum CAT and SOD activities among all groups (p < .05). The present study indicated that Moringa oleifera supplementation could enhance the reproduction performances, elevate protein levels in the colostrum and improve the serum antioxidant indices in both sows and piglets.
Estimation of glomerular filtration rate by plasma clearance of iohexol in healthy horses of various ages
Authors: Lippi Ilaria , Bonelli Francesca , Meucci Valentina , Vitale Valentina , Sgorbini Micaela
Published: October 2019

Background

Plasma clearance of iohexol is a reliable method to assess the glomerular filtration rate (GFR). The relationship between aging and GFR in horses is unclear.

Hypothesis/Objectives

To compare GFR estimated by iohexol clearance in horses of different ages.

Animals

Twenty‐one clinically healthy horses were enrolled.

Methods

Prospective study. Groups: (A) composed by 8 young horses (≤14 years old) with serum creatinine <1.5 mg/dL, (B) by 7 aged horses (≥20 years old) with serum creatinine <1.5 mg/dL, and (C) by 6 aged horses (≥20 years old) with serum creatinine ≥1.5 mg/dL. Iohexol was injected (75.5 mg/kg) through an IV catheter, and plasma samples were collected 5, 30, and 90 minutes later. Plasma clearance of iohexol was obtained by the high‐performance liquid chromatography‐ultraviolet method.

Results

The GFR was 2., 2.1, and 1.45 mL/min/kg (median value) in Groups A, B, and C, respectively. Statistical analysis showed differences between Group A versus C for urea, Group A versus B and A versus C for creatinine, and A versus C for GFR.

Conclusions and Clinical Importance

Glomerular filtration rate was significantly reduced in aged horses with serum creatinine ≥1.5 mg/dL compared to young horses with creatinine <1.5 mg/dL; no differences were obtained between young and aged horses with creatinine <1.5 mg/dL. Glomerular filtration rate evaluation should be considered in aged horses even if the plasma creatinine values are normal.