bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonmedical prescription stimulant users experience subjective but not objective impairments in attention and impulsivity
Authors: Looby Alison , Sant'Ana Sarah
Published: March 2018

Background and Objectives

Nonmedical prescription stimulant use is frequently reported by college students to improve academic performance, yet it is unknown whether users truly experience cognitive impairments that may drive use. This research compared students with at least one report of nonmedical prescription stimulant use and nonusers on both self‐report and objective measures of inattention and impulsivity.

Methods

Two studies examined inattention (N = 155) and impulsivity (N = 115) among college students. Participants completed self‐report questionnaires and cognitive tests, including Digit Span, the Paced Auditory Serial Addition Test, and a Continuous Performance Test to assess inattention, and the Balloon Analogue Risk Task and the Stop Signal Task to assess risk‐taking and impulsivity.

Results

Self‐reports of inattention and impulsive symptoms were significantly higher among users, controlling for gender, GPA, self‐reported ADHD, alcohol use, and drug use; however, no objective differences were found.

Discussion and Conclusions

Nonmedical prescription stimulant users may engage in use to overcome perceived deficits in cognitive abilities despite lack of objective evidence.

Scientific Significance

Understanding discrepancies in objective performance and subjective reports may aid in the development of effective interventions for nonmedical prescription stimulant use. (Am J Addict 2018;27:238–244)
Dermoscopy features of atypical fibroxanthoma: A multicenter study of the International Dermoscopy Society
Authors: Moscarella Elvira , Piana Simonetta , Specchio Francesca , Kyrgidis Athanassios , Nazzaro Gianluca , Eliceche Maite L , Savoia Francesco , Bugatti Leonardo , Filosa Giorgio , Zalaudek Iris , Scarfi Federica , Inskip Mike , Rosendahl Cliff , Pyne John H , Siggs Graeme , Toğral Arzu K , Cabo Horatio , Drlik Lubomir , Lallas Aimilios , Longo Caterina , Argenziano Giuseppe
Published: March 2018

Background/Objectives

Little is known about the dermoscopic features of atypical fibroxanthoma.

Methods

This was a case‐control study. Atypical fibroxanthoma lesions were compared with a control group with non‐melanoma skin cancer.

Results

Altogether 40 atypical fibroxanthoma were collected. Most developed in men (93%), appearing mainly as nodular (63%), amelanotic (93%) and ulcerated (78%) lesions. Most lesions were located on the scalp (55%) and the ears (13%). Dermoscopically, most atypical fibroxanthoma displayed red (83%) and white (70%) structureless areas and irregular linear vessels (43%). A series of features achieved statistical significance when comparing atypical fibroxanthoma with non‐melanoma skin cancer. The presence of red and white structureless areas and white lines, and the absence of yellowish‐white opaque scales, hairpin vessels and arborising vessels were predictive of atypical fibroxanthoma in univariate analysis. However, when squamous cell carcinoma was excluded from the analysis, none of the criteria achieved statistical significance. When basal cell carcinoma was excluded, three variables achieved statistical significance in predicting atypical fibroxanthoma: red, structureless areas, the absence of opaque yellowish‐white scales and absence of white circles.

Conclusions

Atypical fibroxanthomas seem to be barely distinguishable from basal cell carcinoma dermoscopically, but they are more easily distinguishable from a well to moderately differentiated squamous cell carcinoma. A histopathological examination is needed for the final diagnosis.
Low frequency of acetyl salicylic acid hypersensitivity in mastocytosis: The results of a double‐blind, placebo‐controlled challenge study
Authors: Hermans M. A. W. , van der Vet S. Q. A. , van Hagen P. M. , van Wijk R. Gerth , van Daele P. L. A.
Published: March 2018

Background

Patients with mastocytosis are at increased risk of anaphylaxis. The use of nonsteroidal anti‐inflammatory drugs (NSAIDs) is often discouraged because of this reason. However, the actual prevalence and severity of NSAID‐related hypersensitivity among patients with mastocytosis is unknown.

Methods

A double‐blind, placebo‐controlled acetylsalicylic acid (ASA) challenge up to a cumulative dose of 520 mg was performed among adult patients with mastocytosis. In addition, a retrospective search of the entire outpatient cohort was performed to obtain “real‐life” data on NSAID hypersensitivity.

Results

Fifty patients underwent an ASA challenge. Seventy percent had indolent systemic mastocytosis, 18% had mastocytosis in the skin, and 12% had advanced mastocytosis. The ASA challenge was positive in 1 patient who developed urticaria. The additional retrospective chart review revealed that 8 of 191 patients had a history of NSAID‐related hypersensitivity reaction(s), of whom 3 reported severe systemic reactions. All 8 patients had already experienced NSAID‐related hypersensitivity reactions before mastocytosis was diagnosed.

Conclusions

The frequency of ASA hypersensitivity was 2% in a prospective challenge study and 4.1% in a retrospective chart review of 191 patients with mastocytosis. NSAIDs can be administered safely to most patients with mastocytosis. Extra caution should be taken in patients with a history of hypersensitivity reactions to other drugs, or traditional risk factors for NSAID hypersensitivity.
Outlier experienced surgeon’s performances impact on benchmark for technical surgical skills training
Authors: Gallagher Anthony G. , Henn Patrick J. , Neary Paul C. , Senagore Anthony J. , Marcello Peter W. , Bunting Brendan P. , Seymour Neal E. , Satava Richard M.
Published: March 2018

Background

Training in medicine must move to an outcome‐based approach. A proficiency‐based progression outcome approach to training relies on a quantitative estimation of experienced operator performance. We aimed to develop a method for dealing with atypical expert performances in the quantitative definition of surgical proficiency.

Methods

In study one, 100 experienced laparoscopic surgeons’ performances on virtual reality and box‐trainer simulators were assessed for two similar laparoscopic tasks. In study two, 15 experienced surgeons and 16 trainee colorectal surgeons performed one simulated hand‐assisted laparoscopic colorectal procedure. Performance scores of experienced surgeons in both studies were standardized (i.e. Z‐scores) using the mean and standard deviations (SDs). Performances >1.96 SDs from the mean were excluded in proficiency definitions.

Results

In study one, 1–5% of surgeons’ performances were excluded having performed significantly below their colleagues. Excluded surgeons made significantly fewer correct incisions (mean = 7 (SD = 2) versus 19.42 (SD = 4.6), P < 0.0001) and a greater proportion of incorrect incisions (mean = 45.71 (SD = 10.48) versus 5.25 (SD = 6.6), P < 0.0001). In study two, one experienced colorectal surgeon performance was >4 SDs for time to complete the procedure and >6 SDs for path length. After their exclusions, experienced surgeons’ performances were significantly better than trainees for path length: P = 0.031 and for time: P = 0.002.

Conclusion

Objectively assessed atypical expert performances were few. Z‐score standardization identified them and produced a more robust quantitative definition of proficiency.
A “Scented Declaration of Progress”: Globalisation, Afropolitan Imagineering and Familiar Orientations
Authors: Adeniyi Ogunyankin Grace
Published: March 2018

Branded as “Africa's first luxury perfume”, the Scent of Africa perfume is a “scented declaration of progress”. Particularly fascinating is the commercial advertisement for the perfume, which I argue to be an “Afropolitan Imagineering” project that is intended to signal Africa's rise and its new association with global cosmopolitanism. At first glance, the Scent of Africa perfume advertisement seems to point to the ways in which Imagineering projects can reproduce colonial discourses about Africanness. However, in this article, I suggest that we complicate the advertisement and examine its subversive potential to decentre whiteness and celebrate Africanness while writing Africa into the world. Despite this subversion, I conclude that African worlding practices should disinherit the familiarity of Eurocentric geographic determinism that is embedded in Afropolitan Imagineering and instead become informed by afro‐futuristic imaginings and disidentification politics.
The last natural seasonal forests of Indonesia: Implications for forest management and conservation
Authors: Laumonier Yves , Nasi Robert
Published: March 2018

Aim

The status, type and ecology of the vegetation of the southeastern seasonal regions of Indonesia need to be clarified to identify adequate natural resource management and conservation strategies.

Location

Tanimbar archipelago represents a group of islands south of the Banda sea in the Moluccas. The largest is the flat Yamdena (7°36′ S, 131°25′ E).

Methods

Vegetation was interpreted fromLANDSATsatellite data, overlaid with geology and topography for pre‐stratification. Within each strata, forest sites were equally systematically sampled using a network of small 0.2 ha survey plots (60 plots, 7,130 trees) and soil pits sampled for 44 of the vegetation plots. Fisher’s alpha diversity index was used together with ordination techniques to assert differences in forest types.

Results

The forest covered c. 70% of the island, comprising seasonal evergreen forest (SEF), dry deciduous forest (DDF) and moist deciduous forest’ (MDF). TheSEFcanopy (Burseraceae, Meliaceae, Oleaceae and Dilleniaceae) sited around 35 m. The density of trees above 10 cm diameter averaged 632 individuals/ha, the basal area (BA) was 32 m2/ha, and species diversity (SD, Fischer α) 14.84. Rattans are abundant in the understorey. TheMDFexhibited a mixture of evergreen and deciduous big trees while the lower storey was evergreen. Rattans were less common. Distinct family species associations emerged from the ordination (Combretaceae, Fabaceae, Malvaceae and Apocynaceae or Meliaceae, Gnetaceae, Clusiaceae). The density of trees averaged 491 individuals/ha,BA26 m2/ha andSD18.73. The canopy of theDDF(Ebenaceae, Fabaceae, Apocynaceae and Menispermaceae) was around 30 m. During the dry season all tree species shed their leaves. The density of trees averaged 552 individuals/ha,BA20 m2/ha andSD11.58.

Conclusions

The last natural seasonal forests of Indonesia are nowadays only found in the Tanimbar Archipelago. The existence of three contrasted seasonal forest types on small flat island was remarkable and should be quickly translated into decision making for land zoning, agriculture or forestry development, avoiding approaches applied in the humid region of the country. To succeed however, the ecology of these seasonal forests should quickly become priority areas for research to feed the design of suitable conservation and management strategies.
Multicentre international experience of 532‐nm laser photoselective vaporization with GreenLight XPS in men with very large prostates
Authors: Valdivieso Roger , Hueber Pierre‐Alain , Meskawi Malek , Belleville Eric , Ajib Khaled , Bruyere Franck , Te Alexis E. , Chughtai Bilal , Elterman Dean , Misrai Vincent , Zorn Kevin C.
Published: March 2018

Objectives

To describe peri‐operative results, functional outcomes and complications of laser photoselective vaporization, using the GreenLight system, of prostate glands ≥200 mL in volume.

Methods

Retrospective analysis of a prospectively maintained multicentre database was performed to select a subgroup of patients with very large prostates (volume ≥200 mL) treated with the GreenLight XPS laser. A subgroup of patients with prostate volumes 100–200 mL was used for comparison. International Prostate Symptom Score, maximum urinary flow rate, postvoid residual urine volume and prostate‐specific antigen levels were measured at 6, 12, 24, 36 and 48 months. Durability was evaluated using benign prostatic hyperplasia re‐treatment rate at 12, 24 and 36 months. Additionally, complications were recorded using Clavien–Dindo classification.

Results

A total of 33 patients (38%) had prostates ≥200 mL. Baseline characteristics were similar between patients with prostates ≥200 mL and those with prostates 100–200 mL. Patients with very large prostates (≥200 mL) had longer operating times (129 vs 93 min), less energy delivered, a greater number of fibres used (3 vs 2) and a higher conversion rate to transurethral resection of the prostate (16% vs 4%). In terms of complications and functional outcomes, we did not find any differences between the groups. Retreatment rate was also comparable.

Conclusions

Our results show that PVP GreenLight XPS‐180W is an acceptable technique for very large prostates (≥200 mL); however, operating times, energy delivery, fibres used and conversion to TURP are a concern in this particular subgroup. This should be used for patient counselling and surgery planning.
Serenoa repens + selenium + lycopene vs tadalafil 5 mg for the treatment of lower urinary tract symptoms secondary to benign prostatic obstruction: a Phase IV, non‐inferiority, open‐label, clinical study (SPRITE study)
Authors: Morgia Giuseppe , Vespasiani Giuseppe , Pareo Rosaria M. , Voce Salvatore , Madonia Massimo , Carini Marco , Ingrassia Antonio , Terrone Carlo , Gentile Marcello , Carrino Maurizio , Giannantoni Antonella , Blefari Franco , Arnone Salvatore , Santelli Giorgio , Russo Giorgio I. ,   on behalf of the SPRITE investigators
Published: March 2018

Objective

To compare in a randomised, open‐label, non‐inferiority clinical study, the efficacy and tolerability of Serenoa repens (SeR) + selenium (Se) + lycopene (Ly) (SeR‐Se‐Ly) therapy vs tadalafil 5 mg in men with lower urinary tract symptoms (LUTS).

Patients and methods

From May 2015 to January 2017, 427 patients were enrolled in 21 different centres (International Standard Randomised Controlled Trial Number Register [ISRCTN] 73316039). Inclusion criteria included: age between 50 and 80 years, International Prostate Symptom Score (IPSS) ≥12, maximum urinary flow rate (Qmax) ≤ 15 mL/s, and post‐void residual (PVR) <100 mL. Patients were randomised into two groups in a 2:1 ratio: Group A (SeR‐Se‐Ly, 1 tablet daily for 6 months) and Group B (tadalafil 5 mg, 1 tablet daily for 6 months). The primary endpoint of the study was the non‐inferior variation in the IPSS and Qmax in Group A vs Group B after 6 months of treatment.

Results

In all, 404 patients completed the full protocol. When comparing both therapies, Group A was statistically not inferior to Group B considering the median change in IPSS (−3.0 vs −3.0; P < 0.01), IPSS quality of life (−2.0 vs −2.0; P < 0.05), and Qmax (2.0 vs 2.0 mL/s; P < 0.01). We found statistically significant differences in the increase of at least 3 points in Qmax (38.2% vs 28.1%; P = 0.04) and of at least 30% of Qmax (39.2% vs 27.3%; P < 0.01) in Group A compared to Group B. The percentage of patients with an increase of at least 3 points in the IPSS and a decrease of at least 25% of the IPSS was not statistically different between the two groups. For adverse events, four patients in Group A (1.44%) and 10 in Group B (7.81%) (P < 0.05) reported side‐effects.

Conclusion

We have shown that treatment with SeR‐Se‐Ly was not inferior to tadalafil 5 mg for improving IPSS and Qmax in men with LUTS.
Primary magnetic resonance imaging/ultrasonography fusion‐guided biopsy of the prostate
Authors: Maxeiner Andreas , Kittner Beatrice , Blobel Conrad , Wiemer Laura , Hofbauer Sebastian L. , Fischer Thomas , Asbach Patrick , Haas Matthias , Penzkofer Tobias , Fuller Florian , Miller Kurt , Cash Hannes
Published: March 2018

Objective

To examine the performance of a primary magnetic resonance imaging (MRI)/ultrasonography (US) fusion‐guided targeted biopsy (TB), and in combination with an added systematic biopsy (SB).

Patients and Methods

Analysis of 318 consecutive biopsy‐naïve men with suspicious multiparametric MRI (mpMRI; Prostate Imaging Reporting and Data System [PI‐RADS] score ≥3) undergoing transrectal TB and 10‐core SB between January 2012 and December 2016. The indication for performing mpMRI was based on clinical parameters and decided by the treating urologist before admission. TB was performed with a sensor‐based MRI/US fusion‐guided platform. Clinically significant prostate cancer was defined as Gleason score ≥4 + 3 = 7 (International Society of Urological Pathology Grade [ISUP] grade 3) or maximum cancer core length of ≥6 mm.

Results

A median (interquartile range) of 14 (13–14) biopsies per case were taken. The overall cancer detection rate (CDR) was 77% (245/318). The TB alone detected 67% of prostate cancers and the SB alone detected 70%. The PI‐RADS dependent CDR for the combination of TB/SB were 38% (21/55), 78% (120/154) and 95% (104/109) for PI‐RADS scores of 3/4/5, respectively. Clinically significant prostate cancer was diagnosed by the combination of TB and SB in 195 men (61%) and by TB alone in 163 cases (51%). The number of missed or underestimated prostate cancers with a Gleason score ≥8 for TB alone was 31 (10%, P < 0.001) and 21 (7%, P < 0.001) for SB alone in comparison with the results of the combination of TB and SB. The rate of insignificant prostate cancer was comparable for the combination of TB and SB and TB alone (50/318, 16% vs 50/318, 16%).

Conclusions

Pre‐biopsy mpMRI is of incremental value in increasing the detection of clinically significant prostate cancer in biopsy‐naïve patients with suspicion of prostate cancer. Combining TB with SB further improved the diagnostic accuracy without increasing the rate of insignificant prostate cancer.
A submerged pine forest from the early Holocene in the Mecklenburg Lake District, northern Germany
Authors: Kaiser Knut , Oldorff Silke , Breitbach Carsten , Kappler Christoph , Theuerkauf Martin , Scharnweber Tobias , Schult Manuela , Küster Mathias , Engelhardt Christof , Heinrich Ingo , Hupfer Michael , Schwalbe Grit , Kirschey Tom , Bens Oliver
Published: March 2018

For the first time, evidence of a submerged pine forest from the early Holocene can be documented in a central European lake. Subaquatic tree stumps were discovered in Lake Giesenschlagsee at a depth of between 2 and 5 m using scuba divers, side‐scan sonar and a remotely operated vehicle. Several erect stumps, anchored to the ground by roots, represent an in situ record of this former forest. Botanical determination revealed the stumps to be Scots pine (Pinus sylvestris) with an individual tree age of about 80 years. The trees could not be dated by means of dendrochronology, as they are older than the regional reference chronology for pine. Radiocarbon ages from the wood range from 10 880±210 to 10 370±130 cal. a BP, which is equivalent to the mid‐Preboreal to early Boreal biozones. The trees are rooted in sedge peat, which can be dated to this period as well, using pollen stratigraphical analysis. Tilting of the peat bed by 4 m indicates subsidence of the ground due to local dead ice melting, causing the trees to become submerged and preserved for millennia. Together with recently detected Lateglacial in situ tree occurrences in nearby lakes, the submerged pine forest at Giesenschlagsee represents a new and highly promising type of geo‐bio‐archive for the wider region. Comparable in situ pine remnants occur at some terrestrial (buried setting) and marine (submerged setting) sites in northern central Europe and beyond, but they partly differ in age. In general, the in situ pine finds document shifts of the zonal boreal forest ecosystem during the late Quaternary.
Association between the age of solid food introduction and eczema: A systematic review and a meta‐analysis
Authors: Waidyatillake N. T. , Dharmage S. C. , Allen K. J. , Bowatte G. , Boyle R. J. , Burgess J. A. , Koplin J. J. , Garcia‐Larsen V. , Lowe A. J. , Lodge C. J.
Published: March 2018

Introduction

Eczema is a common childhood ailment responsible for a considerable disease burden. Both timing of introduction to solid food and allergenic food are believed to be related to childhood eczema. Despite the growing body of evidence, the relationship between timing of any solid food introduction (allergenic and/or non‐allergenic) and development of eczema has not previously been systematically reviewed.

Methods

PubMed and EMBASE databases were searched using food and eczema terms. Two authors selected papers according to the inclusion criteria and extracted information on study characteristics and measures of association. Meta‐analyses were performed after grouping studies according to the age and type of exposure.

Results

A total of 17 papers met the inclusion criteria, reporting results from 16 study populations. Of these, 11 were cohort studies, 2 case‐controls, 1 cross‐sectional study and 2 randomized controlled trials. Limited meta‐analyses were performed due to heterogeneity between studies. Timing of solid food introduction was not associated with eczema. One randomized controlled trial provided weak evidence of an association between early allergenic (around 4 months) food introduction and reduced risk of eczema.

Conclusions

The available evidence is currently insufficient to determine whether the timing of introduction of any solid food influences the risk of eczema.
Combinations of Simple Mechanisms Explain Diverse Strategies in the Freehand Writing of Memorized Sentences
Authors: Cheng Peter C.‐H. , van Genuchten Erlijn
Published: March 2018

Individual differences in the strategies that control sequential behavior were investigated in an experiment in which participants memorized sentences and then wrote them by hand, in a non‐cursive style. Thirty‐two participants each wrote eight sentences, which had hierarchical structures with five levels. The dataset included over 31,000 letters. Despite the deliberately constrained nature of the task and stimuli, 23 patterns of behavior were identified from the durations of pauses that occurred before the inscription of letters at four chunk levels, spanning letters, words, phrases, and sentences. A critical path task analytic model, Graphical Production of Memorized Sentences (GPoMS), shows that the control of writing relies on cues that continuously switch between motor actions and chunk retrievals in a just‐in‐time fashion at the level of letter information. GPoMS explains the individual differences in terms of variants of a motor production mechanism and variants of a chunk retrieval mechanism, which involve varying degrees of parallelism between cognitive actions and motor actions. A graphical technique for constructing GPoMS models was developed that enabled the estimation of ongoing working memory demands during production.
The effect of estate tax change on the controlling shareholding structure and corporate value of family firms
Authors: Yeh Yin‐Hua , Liao Chen‐Chieh
Published: March 2018

Manuscript type

Empirical

Research question/issue

Estate tax planning has always been a primary concern of large shareholders when arranging the controlling shareholding structure of family firms. This paper provides evidence on the effect of a drastic change in estate tax on the shareholding structure of family‐controlled firms in Taiwan, as well as the impact of these changes on the firms' corporate value. We examine a 2008 policy change in Taiwan that substantially reduced the estate tax from a maximum rate of 50% to a single tax rate of 10%.

Research findings/insights

We analyze a 12‐year period from 2002 to 2014 looking at data of family‐controlled, listed companies with IPOs prior to 2001. The empirical results reveal a reduced motivation among controlling families to circumvent estate tax through altering the shareholding structure after the law change. The results also reveal a positive impact on firm value as a result of the reduction in the tax burden of controlling families. These findings contribute to the family firm and tax literature and provide insight into the effects of tax policy change on the controlling structure of family firms and the consequent benefits on firm value.

Theoretical/academic implications

To the best of our knowledge, this paper is the first empirical study that establishes a significant relationship between estate tax and tax‐avoidance behaviors reflected in the change of the shareholding structure of a family firm. Many research topics linking estate tax with other corporate governance issues in family firms are here unexplored.

Practitioner/policy implications

For the policymaker, this study highlights the increase of firm value due to a reduction in the estate tax rate. Moreover, a tax‐friendly environment can help the controlling family commit themselves to the proper management of the firm instead of expending effort on tax minimization to safeguard their wealth.
Lysosomal acid lipase promotes cholesterol ester metabolism and drives clear cell renal cell carcinoma progression
Authors: Wang Jun , Tan Mingyue , Ge Jifu , Zhang Ping , Zhong Jie , Tao Le , Wang Qiong , Tong Xuemei , Qiu Jianxin
Published: March 2018

Objectives

Clear cell renal cell carcinoma (ccRCC) is characterized histologically by accumulation of cholesterol esters, cholesterol and other neutral lipids. Lysosomal acid lipase (LAL) is a critical enzyme involved in the cholesterol ester metabolism. Here, we sought to determine whether LAL could orchestrate metabolism of cholesterol esters in order to promote ccRCC progression.

Materials and methods

Quantitative reverse‐transcription PCR and western blots were conducted to assess the expression of LAL in human ccRCC tissues. We analysed the relationship between LAL levels and patient survival using tissue microarrays. We used cell proliferation assays, colony formation assays, cell death assays, metabolic assays and xenograft tumour models to evaluate the biological function and underlying mechanisms.

Results

LAL was up‐regulated in ccRCC tissue. Tissue microarray analysis revealed higher levels of LAL in advanced grades of ccRCC, and high LAL expression indicated lower patient survival. Suppressing LAL expression not only blocked the utilization of cholesterol esters but also impaired proliferation and cellular survival. Furthermore, immunohistochemistry staining showed that LAL expression was correlated with Akt phosphorylation. Suppressing LAL expression decreased the phosphorylation level of Akt and Src and reduced the level of 14,15‐epoxyeicosatrienoic acids in ccRCC cells. Supplement of 14,15‐epoxyeicosatrienoic acids rescued proliferation in vitro and in vivo.

Conclusions

LAL promoted cell proliferation and survival via metabolism of epoxyeicosatrienoic acids and activation of the Src/Akt pathway.
Acute cardiac events in severe community‐acquired pneumonia: A multicenter study
Authors: Cilli Aykut , Cakin Ozlem , Aksoy Emine , Kargin Feyza , Adiguzel Nalan , Karakurt Zuhal , Ergan Begum , Mersin Seda , Bozkurt Selen , Ciftci Fatma , Cengiz Melike
Published: March 2018

Introduction

An increased risk of cardiovascular complications has been defined in community‐acquired pneumonia (CAP), but limited data is available for patients with severe CAP.

Objective

The aim of the present study was to define the prevalence, characteristics, risk factors and impact on mortality of acute cardiac events in patients with severe CAP during short and long term.

Method

This investigation was a multicenter, retrospective cohort sudy of patients with severe CAP. Cardiac events were defined as cardiac arrhytmia, congestive heart failure and myocardial infarction. A logistic regression analysis was performed to identify predictors for acute cardiac events and mortality.

Results

Of 373 patients (mean age 68 ± 16, 61.4% male), 56 (15%) developed a cardiac event (43 arrhythmia, 11 congestive heart failure and 2 myocardial infarction). Patients who developed an acute cardiac event were older, had more severe disease, pleural effusion, hypoalbuminemia, hyponatremia and more acidosis. Also, beta‐blocker and diuretic use were more significant in these patients. In‐hospital mortality was significantly higher in patients who developed cardiac events (29.6% vs 11%, P < .001). According to the logistic regression analysis, haloperidol, vasopressor or diuretic use, hypoalbuminemia and age were the predictors for acute cardiac events. Acute cardiac events were significantly associated with in‐hospital mortality (OR 2.1; 95%CI 1.03‐4.61, P = .04), but not associated with 90‐day mortality.

Conclusion

Our findings demonstrated that acute cardiac events are seen in a substantial proportion of patients with severe CAP and their occurence significantly associated with in‐hospital mortality.
Feminist Activism and the Politics of Reform: When and Why Do States Respond to Demands for Gender Equality Policies?
Authors: Goetz Anne Marie , Jenkins Rob
Published: March 2018

Under what conditions is gender equality policy advocacy successful? This article examines a segment of the largely quantitative comparative political science literature that seeks to answer this question. Recent scholarship emphasizes such factors as the strength of women's movements and the forms of opposition to which their policy demands give rise. However, one consequence of this approach is that the role of strategic choices made by feminist policy advocates is underestimated in explaining their successes. The article argues that understanding variation in the outcomes achieved by women's rights advocates requires close attention to the strategic capacity of policy entrepreneurs, assessed in terms of three inter‐related activities: (1) ‘framing’ policy demands; (2) forming and managing civic alliances; and (3) engaging with state entities without compromising organizational autonomy.
Global Agendas, Local Norms: Mobilizing around Unpaid Care and Domestic Work in Asia
Authors: Rao Nitya
Published: March 2018

This article explores the articulation and framing of unpaid care work and the mobilization around it at two spatial scales, the global and national. For the latter it focuses on three of the largest and most diverse countries in Asia — India, China and Indonesia. While the concept of unpaid care work has received considerable attention in international development discourse, it is rarely found in feminist mobilization and advocacy across these countries. The article asks why this issue remains largely excluded from women's political agendas. It also explores how it is framed when it is included. While most organizations recognize women's double burden and the importance of domestic labour, they do not consider ‘unpaid care work’ as a legitimate political issue around which to mobilize. Rather, it is framed, if at all, as part of other political agendas, such as the rights of the elderly (in China), the rights to social protection, especially childcare and maternity entitlements (in India), or the right to equal opportunities within marriage (in Indonesia). The study analyses the differences in framing, the conceptualization of gender equality embedded therein, and the implications for policy.
Distinct gene expression pathways in islets from individuals with short‐ and long‐duration type 1 diabetes
Authors: Mastracci Teresa L. , Turatsinze Jean‐Valery , Book Benita K. , Restrepo Ivan A. , Pugia Michael J. , Wiebke Eric A. , Pescovitz Mark D. , Eizirik Decio L. , Mirmira Raghavendra G.
Published: March 2018

Aims

Our current understanding of the pathogenesis of type 1 diabetes (T1D) arose, in large part, from studies using the non‐obese diabetic (NOD) mouse model. In the present study, we chose a human‐focused method to investigate T1D disease mechanisms and potential targets for therapeutic intervention by directly analysing human donor pancreatic islets from individuals with T1D.

Materials and Methods

We obtained islets from a young individual with T1D for 3 years and from an older individual with T1D for 27 years and performed unbiased functional genomic analysis by high‐depth RNA sequencing; the T1D islets were compared with islets isolated from 3 non‐diabetic donors.

Results

The islets procured from these T1D donors represent a unique opportunity to identify gene expression changes in islets after significantly different disease duration. Data analysis identified several inflammatory pathways up‐regulated in short‐duration disease, which notably included many components of innate immunity. As proof of concept for translation, one of the pathways, governed by IL‐23(p19), was selected for further study in NOD mice because of ongoing human trials of biologics against this target for different indications. A mouse monoclonal antibody directed against IL‐23(p19) when administered to NOD mice resulted in a significant reduction in incidence of diabetes.

Conclusion

While the sample size for this study is small, our data demonstrate that the direct analysis of human islets provides a greater understanding of human disease. These data, together with the analysis of an expanded cohort to be obtained by future collaborative efforts, might result in the identification of promising novel targets for translation into effective therapeutic interventions for human T1D, with the added benefit of repurposing known biologicals for use in different indications.
A late presentation of congenital cardiac anomaly: Accessory chordae from the left atrium causing severe mitral regurgitation
Authors: D'Onghia Giovanni , Martin Marta , Mancini Maria Teresa , Quintarelli Silvia , Cozza Adele , Guarracini Fabrizio , Bonmassari Roberto
Published: March 2018

Mitral regurgitation secondary to accessory mitral valve (MV) chordae of the left atrium is an extremely rare congenital disease. A 85‐year‐old female (NYHA I–II) was hospitalized for investigations. An echocardiogram showed calcification of the MV with mild stenosis and moderate regurgitation. Transesophageal three‐dimensional echocardiogram revealed a band‐like structure extending from the distal third of the anterior wall of the left atrium to the MV. This accessory chordae determined severe systolic regurgitation and mild mitral stenosis. The patient was referred for consideration of cardiac surgery but was refused for comorbidities and anatomy. Usually aberrant chordae determinant valvulopathies are detected and treated at a much younger age. The delay of the symptoms could be explained in our case with the progressive growth and dilatation of the left atrium causing traction of the aberrant chord resulting in an increase in the leaflet prolapse and regurgitation.
Traumatic dental injuries—Prevalence and severity among 16‐year‐old pupils in western Norway
Authors: Bratteberg Magnus , Thelen Dorina S. , Klock Kristin S. , Bårdsen Asgeir
Published: March 2018

Background/Aims

Published data on prevalence and severity of traumatic dental injuries (TDI) in Norway are limited. The aims of this study were to assess prevalence, distribution and severity of TDI in the permanent dentition of 16‐year‐old pupils in western Norway.

Material and methods

A retrospective longitudinal study, including historical clinical data, was conducted among 16‐year‐old high school pupils in the County of Hordaland, western Norway. First‐grade pupils attending high school, born in 1997, were invited to participate (n = 5184). Consent was given to access their dental records in the Public Dental Health Service in Hordaland, where information regarding TDI (diagnosis and treatment) and radiographs was interpreted. Only TDIs to anterior teeth were recorded (canine to canine in the maxilla and mandible) and classified using a modified version of the WHO’s classification.

Results

A total of 2055 participants were included (response rate 40%). TDI prevalence was 16.4% (338 pupils), with the maxillary central incisors most affected (64.7%). A total of 637 teeth were involved. Boys were more prone to injury than girls (P < 0.05). Severity of TDI was divided into 3 groups (mild, moderate and severe), with the following distribution: 563 mild (88.4%), 39 moderate (6.1%) and 35 severe (5.5%). Peak age for TDI was 8‐10 years (50.9%).

Conclusions

Prevalence of TDI among Norwegian adolescents was moderate. Milder injuries were more frequent than moderate and severe injuries. Age and gender were risk factors with regard to TDI. Seasonal influence on the occurrence of TDI was not statistically significant.
Variability in the performance of juvenile Chinook salmon is explained primarily by when and where they resided in estuarine habitats
Authors: Chittaro Paul , Johnson Lyndal , Teel David , Moran Paul , Sol Sean , Macneale Kate , Zabel Richard
Published: March 2018

Estuarine habitats provide rearing opportunities for the juvenile life stage of anadromous fishes. Because survival is positively correlated with juvenile performance, these estuarine habitats play an important role in population abundance and productivity. To provide information for the recovery of several depressed stocks of Chinook salmon in the Columbia River Basin, we sought to identify the factors that explain variability in performance. Using otolith‐derived estimates of juvenile somatic growth rate as an index of recent performance, we observed a negative nonlinear relationship between growth rate and day of year, and a decreasing and increasing trend of growth rate over the 8 years of this study and distance from the river mouth respectively. Using a generalised linear modelling approach, we found that variability in juvenile somatic growth rate was best explained by where and when individuals were collected, their body size, contaminant loads, stock of origin, and whether a fish was hatchery produced or unmarked. Lastly, we argue that a considerable improvement to the growth rate of juveniles in estuarine habitats is physiologically possible. The results of this 8‐year study provide a baseline of the performance of juvenile Chinook salmon to evaluate habitat restoration programs and to compare against future anthropogenic conditions.
Lenalidomide as immune adjuvant to a dendritic cell vaccine in chronic lymphocytic leukemia patients
Authors: Palma Marzia , Hansson Lotta , Mulder Tom A. , Adamson Lars , Näsman‐Glaser Barbro , Eriksson Ingrid , Heimersson Kia , Ryblom Harriet , Mozaffari Fariba , Svensson Ann , Gentilcore Giusy , Österborg Anders , Mellstedt Håkan
Published: March 2018

Objectives

We previously showed that immunization with ex vivo‐ generated autologous dendritic cells loaded with apoptotic tumor cells (Apo‐DC) potentiated tumor‐specific immunity in chronic lymphocytic leukemia (CLL) patients. Here, we evaluated safety and immunogenicity of Apo‐DC in combination with lenalidomide, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), and low‐dose cyclophosphamide (CTX).

Methods

Ten previously untreated patients with slowly progressing CLL received 5 Apo‐DC vaccinations and lenalidomide orally for 24 weeks either alone (cohort I, n = 5) or together with subcutaneous GM‐CSF and intravenous CTX (cohort II, n = 5). Tumor‐specific T‐cell responses were measured by proliferation and IFN‐γ ELISPOT assays. Immune monitoring was performed by flow cytometry.

Results

Dose‐limiting toxicity was observed in 3/10 patients, 2 in cohort I and one in cohort II. One patient developed autoimmune hemolytic anemia and another grade 4 thrombocytopenia. Vaccine‐induced immune responses were seen in 5/5 and 4/5 patients in cohort I and II, respectively. The expression of immune checkpoints on T cells did not change significantly.

Conclusions

Lenalidomide alone or in combination with GM‐CSF and low‐dose CTX as immune adjuvant to the Apo‐DC vaccine elicited tumor‐specific T‐cell responses in CLL patients. However, unexpected toxicity was observed and caution is suggested in further exploring this drug as immune adjuvant in CLL.
Adenosine A2A receptors modulate the dopamine D2 receptor‐mediated inhibition of synaptic transmission in the mouse prefrontal cortex
Authors: Real Joana I. , Simões Ana Patrícia , Cunha Rodrigo A. , Ferreira Samira G. , Rial Daniel
Published: March 2018

Prefrontal cortex (PFC) circuits are modulated by dopamine acting on D1‐ and D2‐like receptors, which are pharmacologically exploited to manage neuropsychiatric conditions. Adenosine A2A receptors (A2AR) also control PFC‐related responses and A2AR antagonists are potential anti‐psychotic drugs. As tight antagonistic A2AR–D2R and synergistic A2AR–D1R interactions occur in other brain regions, we now investigated the crosstalk between A2AR and D1/D2R controlling synaptic transmission between layers II/III and V in mouse PFC coronal slices. Dopamine decreased synaptic transmission, a presynaptic effect based on the parallel increase in paired‐pulse responses. Dopamine inhibition was prevented by the D2R‐like antagonist sulpiride but not by the D1R antagonist SCH23390 and was mimicked by the D2R agonist sumanirole, but not by the agonists of either D4R (A‐412997) or D3R (PD128907). Dopamine inhibition was prevented by the A2AR antagonist, SCH58261, and attenuated in A2AR knockout mice. Accordingly, triple‐labelling immunocytochemistry experiments revealed the co‐localization of A2AR and D2R immunoreactivity in glutamatergic (vGluT1‐positive) nerve terminals of the PFC. This reported positive A2AR–D2R interaction controlling PFC synaptic transmission provides a mechanistic justification for the anti‐psychotic potential of A2AR antagonists.
Lysosomal LAMP1 immunoreactivity exists in both diffuse and neuritic amyloid plaques in the human hippocampus
Authors: Hassiotis Sofia , Manavis Jim , Blumbergs Peter C. , Hattersley Kathryn J. , Carosi Julian M. , Kamei Makoto , Sargeant Timothy J.
Published: March 2018

Lysosomal vesicles around neuritic plaques are thought to drive Alzheimer's disease by providing ideal microenvironments for generation of amyloid‐β. Although lysosomal vesicles are present at every amyloid plaque in mouse models of Alzheimer's disease, the number of amyloid plaques that contain lysosomal vesicles in the human brain remains unknown. This study aimed to quantify lysosomal vesicles at amyloid plaques in the human hippocampus. Lysosome‐associated membrane protein 1 (LAMP1)‐positive vesicles accumulated in both diffuse (Aβ42‐positive/AT8‐negative) and neuritic (Aβ42‐positive/AT8‐positive) plaques in all regions were analysed. In contrast to mouse models of Alzheimer's disease, however, not all amyloid plaques accumulated LAMP1‐positive lysosomal vesicles. Even at neuritic plaques, LAMP1 immunoreactivity was more abundant than phospho‐tau (AT8). Further, lysosomal vesicles colocalised weakly with phospho‐tau such that accumulation of lysosomal vesicles and phospho‐tau appeared to be spatially distinct events that occurred within dystrophic neurites. This quantitative study shows that diffuse plaques, as well as neuritic plaques, contain LAMP1 immunoreactivity in the human hippocampus.
Induction of IL‐10‐balanced immune profiles following exposure to LTA from Staphylococcus epidermidis
Authors: Volz Thomas , Kaesler Susanne , Draing Christian , Hartung Thomas , Röcken Martin , Skabytska Yuliya , Biedermann Tilo
Published: March 2018

Staphylococcus epidermidis colonises human skin without apparent inflammation, but a dominance of S. epidermidis and S. aureus is characteristic of cutaneous microbial dysbiosis in atopic dermatitis (AD). While S. aureus can trigger AD, the role of S. epidermidis is less understood. We characterised consequences of innate immune sensing of lipoteichoic acid (LTA) preparations derived from S. epidermidis (epi‐LTA) or S. aureus (aureus‐LTA). Therefore, dendritic cell (DC) activation and consecutive priming of antigen‐specific T cells following exposure of DC to epi‐LTA or aureus‐LTA were investigated. Mimicking acute AD, exposure of DC to IL‐4 and LTAs was analysed. Exposure to epi‐LTA or aureus‐LTA activated human immune cells and murine dendritic cells (DCs) via TLR2/MyD88, however, resulting in divergent immune profiles. Differences between LTAs were significant for IL‐6, IL‐12p40 and IL‐12p70 but not for IL‐10, which was best reflected by the IL‐12p70‐to‐IL‐10 ratio being IL‐10‐balanced for epi‐LTA but pro‐inflammatory for aureus‐LTA. LTA‐exposed DCs activated CD4+ T cells; however, while T‐cell‐derived IL‐10 was equivalent between LTAs, IFN‐γ and IL‐17 were significantly higher for aureus‐LTA. Mimicking acute AD by exposing DCs to IL‐4 and LTAs revealed that IL‐4 significantly and uniformly suppressed epi‐LTA‐induced cytokine production, keeping the IL‐12p70‐to‐IL‐10 ratio balanced. In contrast, exposure of DCs to aureus‐LTA and IL‐4 enhanced IL‐12p70 but suppressed IL‐10 levels, further unbalancing the IL‐12p70‐to‐IL‐10 ratio. These data demonstrate opposing immune consequences following exposure to staphylococcal LTAs. Epi‐LTA induced IL‐10‐balanced, aureus‐LTA pro‐inflammatory immune profiles.
NDRG1 and FOXO1 regulate endothelial cell proliferation in infantile haemangioma
Authors: Byun Ji Won , An Hye Young , Yeom Seung Dohn , Lee Seok Jong , Chung Ho Yun
Published: March 2018

The etiopathogenesis of infantile haemangioma has not been well understood, and it is accepted that angiogenic mediator dysregulation is the main contributor to the abnormal haemangioma capillary formation. The role of NDRG1, a hypoxia‐inducible protein; FOXOs, which are tumor suppressor proteins; and the mTOR complex 2 pathway in infantile haemangioma have not been studied yet. The purpose of this study was to investigate NDRG1 and FOXO1 expression in the infantile haemangioma and the correlation of these proteins with proliferation and involution. Primary endothelial cells were obtained, with parental agreement, from 12 infantile haemangioma patients during surgery; 6 patients had proliferating infantile haemangiomas and 6 had involuting IHs. We compared the infantile haemangioma tissues and primary endothelial cells with human vein endothelial cells using microarrays, real‐time PCR, Western blotting and immunohistochemical staining. Our data indicated that FOXO1 expression was downregulated in proliferating infantile haemangioma tissue. We found that the expression of NDRG1, a molecule upstream of the FOXO1 pathway, increased during haemangioma proliferation. NDRG1 knockdown decreased haemangioma endothelial cell proliferation and downregulated c‐MYC oncoprotein levels. Our findings suggest that NDRG1 positively regulates haemangioma proliferation. FOXO1 dysregulation plays an important role in infantile haemangiomas pathogenesis.