bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum S100B as a Surrogate Biomarker in the Diagnoses of Burnout and Depression in Emergency Medicine Residents
Authors: Gulen Bedia , Serinken Mustafa , Eken Cenker , Karcıoglu Özgür , Kucukdagli Okkes Taha , Kilic Elif , Akpinar Guleser , Nogay Suleyman , Kuh Mahmut
Published: March 2016

Objectives

Burnout syndrome is recognized as a major global problem among emergency healthcare workers as it causes prevalent fatigue, job separations, and disappointment. The objective of this study was to investigate the relationship of the glial marker S100B in sera of emergency physicians with burnout syndrome and depression.

Methods

This was a prospective observational study of emergency medicine residents in three distinct university‐based departments of emergency medicine. S100B levels were measured before and after the shifts. In addition, the resident completed the Maslach Burnout Inventory (MBI) and the Beck Depression Inventory (BDI) prior to starting the shift. S100B levels were compared to the occurrence of burnout syndrome and depression as measured by the MBI and BDI.

Results

Forty‐eight of 53 emergency medicine residents actively working in the three university‐based EDs participated in the study. The majority of the sample had BDI scores compatible with severe depression (n = 37, 77.1%). The median scores of MBI for emotional exhaustion, depersonalization, and personal accomplishment were 29 (interquartile range [IQR] = 25 to 33), 14 (IQR = 12 to 18), and 26.5 (IQR = 22 to 31), respectively. S100B levels were found to correlate best with scores of BDI and emotional exhaustion in burnout syndrome. The difference between median S100B levels recorded in the residents with severe depression and moderate depression was found statistically significant (median [IQR] = 150 [145 to 151] vs. 135 [128 to 140]; p = 0.0005). This is also true for S100B levels detected before and after night shifts (median [IQR] = 146 [136.5 to 153.2] and 149.5 [139–158], respectively; difference = 3, 95% confidence interval = 2 to 4 [p = 0.001]).

Conclusions

S100B levels correlate with depression scores and emotional exhaustion in burnout syndrome. The findings suggest that S100B can be used as a marker to screen emergency medicine residents and detect individuals with high risk for depression and burnout syndrome.
Standardization of allergen products: 3. Validation of candidate European Pharmacopoeia standard methods for quantification of major birch allergen Bet v 1
Authors: Kaul S. , Zimmer J. , Dehus O. , Costanzo A. , Daas A. , Buchheit K. H. , Asturias J. A. , Barber D. , Carnés J. , Chapman M. , Dayan‐Kenigsberg J. , Döring S. , Führer F. , Hanschmann K. M. , Holzhauser T. , Ledesma A. , Moingeon P. , Nony E. , Pini C. , Plunkett G. , Reese G. , Sandberg E. , Sander I. , Strecker D. , Valerio C. , van Ree R. , Vieths S.
Published: March 2016

Background

The BSP090 project aims at establishing European Pharmacopoeia Reference Substances in combination with the corresponding ELISA methods for the quantification of major allergens in allergen products. Two sandwich ELISAs proved suitable for quantification of Bet v 1, the major birch pollen allergen, in preceding phases of BSP090.

Methods

Two Bet v 1‐specific ELISA systems were compared with respect to accuracy and precision in a ring trial including 13 laboratories. Model samples containing recombinant rBet v 1.0101 as well as native birch pollen extracts were measured independently at least three times in each facility. The assessment was completed with a comparative quantification of Bet v 1 in 30 marketed birch allergen products in one laboratory, simulating the future use as reference method.

Results

In the collaborative study, both candidate ELISAs confirmed their suitability to quantify recombinant and native Bet v 1. ELISA‐A showed higher precision and lower interlaboratory variability, yet ELISA‐B exhibited slightly higher accuracy. Subsequent parallel measurement of Bet v 1 in a panel of ‘real‐life’ birch allergen products indicated better repeatability of ELISA‐B. Both systems detected substantial differences in Bet v 1 content between allergen products, but the effect was more pronounced using ELISA‐B due to persistently higher values compared to ELISA‐A.

Conclusions

In the collaborative study, no deciding differences were observed between the two candidate ELISAs. Further comparison under conditions simulating the intended use combined with the criterion of long‐term availability enabled the selection of one Bet v 1‐specific ELISA for proposal as European Pharmacopoeia standard method.
T‐Wave Alternans, Heart Rate Turbulence, and Ventricular Ectopy in Standard versus Daily Hemodialysis: Results from the FHN Daily Trial
Authors: Kaplan Rachel M. , Herzog Charles A. , Larive Brett , Subacius Haris , Nearing Bruce D. , Verrier Richard , Passman Rod S.
Published: March 2016

Background

Hemodialysis (HD) patients are at high risk of sudden cardiac death (SCD). HD 6‐times/week (6x/wk) may reduce SCD risk compared to usual 3‐times/week HD (3x/wk) by mechanisms unknown. T‐wave alternans (TWA), heart rate turbulence (HRT), and ventricular ectopy (VE) are elevated in HD patients, but their response to 6x/wk HD has not been assessed.

Methods

Baseline and 1‐year Holter recordings were analyzed from enrollees in the Frequent Hemodialysis Network Daily Trial, a randomized trial comparing 3x/wk to 6x/wk in 245 chronic HD patients. TWA, HRT, and VE were assessed using MARS software.

Results

Sixty‐eight patients (34 with 6x/wk) had complete baseline and 1‐year Holter recordings. Mean age was 50 ± 13 years and 38% were female. Maximum TWA in the 3x/wk and 6x/wk groups were 52.4 μV at baseline and 51.2 μV at 1‐year versus 54.0 and 49.9 μV, respectively (P = 0.28). The proportion of abnormal HRT (scores of 1 or 2) in the 3x/wk group decreased from 65% to 56% at 1‐year versus 53% to 53% in the 6x/wk group (P = 0.58). Mean %VE changed from 1.6% to 2.9% in the 3x/wk group from baseline to 1‐year and from 2.1% to 3.7% in the 6x/wk group (P = 0.85).

Conclusions

There were no significant differences in HRT or VE at 1‐year in chronic HD patients randomized to 6x/wk versus 3x/wk and a trend in TWA reduction. Additional studies are needed to evaluate the impact and mechanisms of SCD in HD.
De Winter Electrocardiographic Pattern Related with a Non‐Left Anterior Descending Coronary Artery Occlusion
Authors: Montero Cabezas José M. , Karalis Ioannis , Schalij Martin J.
Published: March 2016

The electrocardiographic pattern consisting of ST‐segment depression and hyperacute T waves in patients with acute chest pain, known as “De Winter pattern,” has been related with the occlusion of the proximal left anterior descending artery (LAD). The association of these findings with the involvement of a different coronary artery has not been described. We present a 53‐year‐old patient with an occlusion of the first diagonal branch and an electrocardiogram showing a “De Winter pattern.” The reported case demonstrates that “De Winter pattern” is not exclusively associated with the occlusion of the proximal segment of the LAD.
Changes in Electrocardiographic P Wave Parameters after Cryoballoon Ablation and Their Association with Atrial Fibrillation Recurrence
Authors: Kizilirmak Filiz , Demir Gultekin Gunhan , Gokdeniz Tayyar , Gunes Haci Murat , Cakal Beytullah , Guler Ekrem , Karaca İbrahim Oguz , Omaygenç Mehmet Onur , Yılmaz Fatih , Olgun Fatih Erkam , Kilicaslan Fethi
Published: March 2016

Background

Changes in P wave parameters after circumferential pulmonary vein isolation (CPVI) have been previously identified. In this study, we aimed to determine the changes in P wave parameters surface electrocardiogram (ECG) after cryoballoon ablation (CBA) for atrial fibrillation (AF) and evaluate their relationship with AF recurrence.

Methods

Sixty‐one patients (mean age 53 ± 11 years, 50.8% male) with paroxysmal AF who underwent CBA were enrolled. A surface ECG was obtained from all patients immediately before the procedure, and repeated 12 hours after the procedure. P wave amplitude (Pamp), P wave duration (Pwd), and P wave dispersion (Pdis) values in preprocedural and postprocedural ECGs were measured and compared. Recurrence rates of AF in 3, 6, and 9 months following ablation were recorded for all patients. Changes in P wave parameters were compared between patients with and without AF recurrence.

Results

Compared to preprocedural measurements, Pamp (from 0.58 ± 0.18 mV at baseline to 0.48 ± 0.17 mV, P < 0.001), Pwd (from 109.72 ± 18.43 ms at baseline to 91.36 ± 22.53 ms, P < 0.001), and Pdis (from 55.44 ± 20.45 ms at baseline to 45.30 ± 15.31 ms, P < 0.001) were significantly decreased after CBA. The difference in Pamp between pre‐ and postprocedural values (∆Pamp) was significantly higher in patients without AF recurrence compared to those with recurrence (0.10 ± 0.06 mV vs 0.04 ± 0.01 mV, P = 0.002). There was no difference in Pwd difference (∆Pwd) and Pdis difference (∆Pdis) between patients with and without AF recurrence (P > 0.05).

Conclusion

Pamp, Pwd, and Pdis parameters exhibited significant decrease after CBA compared to preprocedural measurements. Decreased Pamp was shown to be a predictor for good clinical outcomes following CBA.
Enhanced Recovery After Surgery in elective hip and knee arthroplasty reduces length of hospital stay
Authors: Stowers Marinus D. J. , Manuopangai Lavell , Hill Andrew G. , Gray Jonathon R. , Coleman Brendan , Munro Jacob T.
Published: March 2016

Background

Standardized perioperative care within an Enhanced Recovery After Surgery (ERAS) programme aims to reduce postoperative morbidity and length of hospital stay (LOS). This study evaluated the effect of ERAS in patients undergoing elective, primary total hip and knee arthroplasty (THA and TKA) in a New Zealand public hospital.

Methods

Data collected prospectively on patients who had undergone THA and TKA in an ERAS programme (ERAS: August–December 2013) were compared to a retrospective cohort of patients managed in a traditional perioperative care environment (control: June–August 2012). The Breakthrough Series Model for Improvement provided a framework to implement components of the ERAS protocol. The primary outcome was median LOS. Secondary outcomes included 30‐day readmission rates, complications and cost.

Results

There were 206 patients who met the eligibility criteria (106 ERAS, 100 control). There were no significant differences in baseline characteristics. After the implementation of ERAS, median LOS was reduced by 1 day (5 control versus 4 ERAS; P < 0.001). Short‐term complications were similar (P = 0.372) as were readmission rates (P = 0.258). Cost analysis identified ERAS patients to have reduced cost overall.

Conclusions

ERAS in THA and TKA has been shown to be safe and effective in improving recovery through shorter hospital stay.
Rethinking Land Struggle in the Postindustrial City
Authors: Safransky Sara
Published: March 2016

The racial and cultural politics of land and property are central to urban struggle, but have received relatively little attention in geography. This paper analyzes land struggles in Detroit where over 100,000 parcels of land are classified as “vacant”. Since 2010, planners and government officials have been developing controversial plans to ruralize Detroit's “vacant” neighborhoods as part of a program of fiscal austerity, reigniting old questions of racialized dispossession, sovereignty, and struggles for liberation. This paper analyzes these contentious politics by examining disputes over a white businessman's proposal to build the world's largest urban forest in the center of a Black majority city. I focus on how residents, urban farmers, and community activists resisted the project by making counterclaims to vacant land as an urban commons. They argued that the land is inhabited not empty and that it belonged to those who labored upon and suffered for it. Combining community‐based ethnography with insights from critical property theory, critical race studies, and postcolonial theory, I argue that land struggles in Detroit are more than distributional conflicts over resources. They are inextricable from debates over notions of race, property, and citizenship that undergird modern liberal democracies and ongoing struggles for decolonization.
Families, policy and place in times of austerity
Authors: Jupp Eleanor
Published: March 2016

Families in the UK have played a key role within the ‘third way’ policy regimes of the past two decades, promising to act as arenas of citizenship between the individual and the market. Such a framing has always posed questions about which families are imagined to be capable of this role, with competing constructions of ‘risky’ and ‘resourceful’ families within social policy discourses. Over the past five years UK families have been hit with an array of cuts and reforms to state benefits and other forms of government support. This paper argues that, within this context of austerity, problematic binary constructions in policy discourses are increasing. Certain families and households are relied on to deliver aspects of care, while others are vilified as unstable and ‘troubled’, in ways that view families as individualised and removed from their wider geographies. Against this background it is argued that detailed geographical research into the everyday lives of disadvantaged families can talk back to these powerful representations. This means paying attention to the ways that families navigate everyday landscapes of care, both material and emotional, which are in turn shaped by the unequal resources available, including increasingly unevenly distributed state services.
Asymmetric Mispricing and Regime‐dependent Dynamics in Futures and Options Markets
Authors: Lee Jaeram , Ryu Doojin
Published: March 2016

We examine regime‐dependent price dynamics and mispricing adjustments within the KOSPI200 spot, futures and options markets through an analysis of data from January 2000 to December 2014. Investors exploit mispricing between derivatives and spot markets only if mispricing is sufficiently large. The futures traders take long, rather than short, positions to adjust for mispricing. Mispricing between spot and options markets is adjusted by trading options and not by trading spots. We find the bidirectional information flows between spot and futures markets when the futures‐implied index is sufficiently larger than the spot index. In contrast, no significant lead–lag relationship between spot and options markets exists. Significant asymmetric transaction costs exist in the spot market and this asymmetry has decreased over time.
Effect of candidate gene polymorphisms on reproductive traits in a Large White pig population
Authors: Sato Shuji , Kikuchi Takashi , Uemoto Yoshinobu , Mikawa Satoshi , Suzuki Keiichi
Published: March 2016

The objective of this study was to test for association of candidate single nucleotide polymorphisms (SNPs) with sow prolificacy reproductive traits, such as litter size, ovulation rate and lifetime performance, in gilts of a Large White pig population. Preliminary research on 25 animals selected from the high‐ and low‐performance groups of 347 animals with case‐control studies indicated that seven genes were associated with total number of piglets born (TNB). Six of the seven genes were associated with reproductive traits, including TNB, number of piglets born alive (NBA) and average weight of piglet weaning (AWW). A MBL2 SNP was significantly associated with TNB and NBA in first parity. A CFB SNP was associated with TNB in first parity. An ACE SNP was associated with TNB in first and second parities. An EGF polymorphism was associated with TNB, NBA and AWW in second parity. A KCNC2 polymorphism was significantly associated with TNB and NBA in second parity. A SLC22A5 SNP was associated with TNB and NBA in second parity. Six candidate SNPs were associated with TNB; the only exception was a PRKAG3 polymorphism. A candidate gene approach enables some of these polymorphisms to be used in genetic improvement programs based on marker‐assisted selection.
A Comparison of Practices During the Confinement Period among Chinese, Malay, and Indian Mothers in Singapore
Authors: Fok Doris , Aris Izzuddin M. , Ho Jiahui , Lim Sok Bee , Chua Mei Chien , Pang Wei Wei , Saw Seang‐Mei , Kwek Kenneth , Godfrey Keith M. , Kramer Michael S. , Chong Yap Seng ,   the GUSTO Study Group
Published: March 2016

Background

Confinement (restrictions placed on diet and practices during the month right after delivery) represents a key feature of Asian populations. Few studies, however, have focused specifically on ethnic differences in confinement practices. This study assesses the confinement practices of three ethnic groups in a multi‐ethnic Asian population.

Methods

Participants were part of a prospective birth cohort study that recruited 1,247 pregnant women (57.2% Chinese, 25.5% Malay, and 17.3% Indian) during their first trimester. The 1,220 participants were followed up 3 weeks postpartum at home when questionnaires were administered to ascertain the frequency of adherence to the following confinement practices: showering; confinement‐specific meals; going out with or without the baby; choice of caregiver assistance; and the use of massage therapy.

Results

Most participants reported that they followed confinement practices during the first 3 weeks postpartum (Chinese: 96.4%, Malay: 92.4%, Indian: 85.6%). Chinese and Indian mothers tended to eat more special confinement diets than Malay mothers (p < 0.001), and Chinese mothers showered less and were more likely to depend on confinement nannies during this period than mothers from the two other ethnic groups (p < 0.001 for all). Malay mothers tended to make greater use of massage therapy (p < 0.001), whilst Indian mothers tended to have their mothers or mothers‐in‐law as assistant caregivers (p < 0.001).

Conclusion

Most Singapore mothers follow confinement practices, but the three Asian ethnic groups differed in specific confinement practices. Future studies should examine whether ethnic differences persist in later childrearing practices.
Advances in understanding the pathogenesis of graft‐versus‐host disease
Authors: Magenau John , Runaas Lyndsey , Reddy Pavan
Published: March 2016

Allogeneic haematopoietic stem cell transplantation (HCT) is a potent immunotherapy with curative potential for several haematological disorders. Overcoming the immunological barrier of acute graft‐versus‐host disease (GVHD) remains a fundamental impediment to expanding the efficacy of HCT. GVHD reflects a complex pathological interaction between the innate and adaptive immune systems of the host and donor. Over the past decade there has been a tremendous advancement in our understanding of the cellular and molecular underpinnings of this devastating disease. In this review, we cover several recently appreciated facets of GVHD pathogenesis including novel extracellular mediators of inflammation, immune subsets, intracellular signal transduction, post‐translation modifications and epigenetic regulation. We begin to develop general themes regarding the immunological pathways in GVHD pathogenesis, discuss critical outstanding questions, and explore new avenues for GVHD treatment and prevention.
Targeting childhood, adolescent and young adult non‐Hodgkin lymphoma: therapeutic horizons
Authors: Galardy Paul J. , Bedekovics Tibor , Hermiston Michelle L.
Published: March 2016

Non‐Hodgkin lymphoma (NHL) is the third most common malignancy in children, adolescents and young adults (CAYA). NHL is a diverse set of diseases that arise at key regulatory checkpoints during B or T cell development in the bone marrow, germinal centre or thymus. While advances in the use of conventional cytotoxic agents have led to dramatic improvements in survival, these cures are associated with significant acute and long‐term toxicities. Moreover, the prognosis for CAYA patients with relapsed or refractory NHL remains dismal, with the vast majority dying of their disease. Thanks to a large number of candidate‐based biological studies, together with large‐scale sequencing efforts, there has been an explosion of knowledge regarding the molecular pathophysiology of B‐ and T‐NHL. This has ushered development of a flurry of novel therapeutic approaches that may simultaneously provide new hope for relapsed patients and an opportunity to reduce the therapeutic burden in newly diagnosed CAYA. Here we review a selection of the most promising new therapeutic approaches to these diseases. While the vast majority of these agents are untested in children, on‐going work from many cooperative groups will soon explore their use in paediatric disease, in hope of further improving outcomes while maximizing quality of life.
Incidence and risk factors for Central Nervous System thrombosis in paediatric acute lymphoblastic leukaemia during intensive asparaginase treatment: a single‐centre cohort study
Authors: Duarte Ximo , Esteves Susana , Neto Ana M. , Pereira Filomena
Published: March 2016

Central Nervous System (CNS) thrombosis is a complication of acute lymphoblastic leukaemia (ALL) treatment that is potentially associated with significant morbidity and neurological sequelae. Its presumably multifactorial aetiology is poorly characterized. We conducted a single‐centre, retrospective cohort study on 346 ALL paediatric patients (1–16 years old) treated with asparaginase intensive Dana Farber Cancer Institute (DFCI) protocols from 1998 to 2011. The incidence, risk factors and outcome of CNS thrombosis were evaluated. CNS thrombosis occurred in 3·8% (13/346) of the patients (95% confidence interval 2·0–6·3%). Twelve events were diagnosed during intensification, all of which resolved within 2 weeks without neurological sequelae or significant impact in survival. Obesity (body mass index above 95th percentile) and asparaginase formulation were the only factors associated with CNS thrombosis, with an increase in the odds of event in obese patients [odds ratio (OR) = 3·37; P = 0·064] and a reduction in patients receiving Erwinia asparaginase (OR = 0·12; P = 0·018). No association could be demonstrated for age, gender, DFCI risk‐group, ALL phenotype, steroid or doxorubicin use, central venous line use or CNS radiotherapy. CNS thrombosis is a rare but manageable adverse event without significant sequelae or detrimental effects in survival. Increased awareness is recommended in obese patients particularly during intensive asparaginase use.
Rituximab, bendamustine and lenalidomide in patients with aggressive B‐cell lymphoma not eligible for anthracycline‐based therapy or intensive salvage chemotherapy – SAKK 38/08
Authors: Hitz Felicitas , Zucca Emanuele , Pabst Thomas , Fischer Natalie , Cairoli Anne , Samaras Panagiotis , Caspar Clemens B. , Mach Nicolas , Krasniqi Fatime , Schmidt Adrian , Rothermundt Christian , Enoiu Milica , Eckhardt Katrin , Berardi Vilei Simona , Rondeau Stephanie , Mey Ulrich
Published: March 2016

An increasing number of older patients are suffering from aggressive lymphoma. Effective and more tolerable treatment regimens are urgently needed for this growing patient population. Patients with aggressive lymphoma not eligible for anthracycline‐based first‐line therapy or intensive salvage regimens were treated with the rituximab‐bendamustine‐lenalidomide (R‐BL) regimen (rituximab 375 mg/m2 day 1, bendamustine 70 mg/m2 d 1, 2, lenalidomide 10 mg d 1–21) for six cycles every 4 weeks. Forty‐one patients with a median age of 75 (range 40–94) years were enrolled: 33 patients had substantial co‐morbidities. 13 patients were not eligible for anthracycline‐based first‐line chemotherapy, 28 patients had relapsed/refractory disease. The primary endpoint, overall response, was achieved by 25 (61%) patients (95% confidence interval 45–76%). Grade ≥ 3 toxicity comprised haematological (59%), skin (15%), constitutional (15%) and neurological (12%) events. 9 patients died during trial treatment: 5 from lymphoma progression, 2 from toxicity, 2 with sudden death. After a median follow‐up of 25·9 (interquartile range 20·4–31·6) months, 13 patients were still alive. Median overall survival was 14·5 months. In conclusion, R‐BL can be considered a treatment option for elderly patients with treatment naïve or relapsed/refractory aggressive lymphoma not eligible for standard aggressive regimens.
The genetic landscape of paediatric de novo acute myeloid leukaemia as defined by single nucleotide polymorphism array and exon sequencing of 100 candidate genes
Authors: Olsson Linda , Zettermark Sofia , Biloglav Andrea , Castor Anders , Behrendtz Mikael , Forestier Erik , Paulsson Kajsa , Johansson Bertil
Published: March 2016

Cytogenetic analyses of a consecutive series of 67 paediatric (median age 8 years; range 0–17) de novo acute myeloid leukaemia (AML) patients revealed aberrations in 55 (82%) cases. The most common subgroups were KMT2A rearrangement (29%), normal karyotype (15%), RUNX1‐RUNX1T1 (10%), deletions of 5q, 7q and/or 17p (9%), myeloid leukaemia associated with Down syndrome (7%), PML‐RARA (7%) and CBFB‐MYH11 (5%). Single nucleotide polymorphism array (SNP‐A) analysis and exon sequencing of 100 genes, performed in 52 and 40 cases, respectively (39 overlapping), revealed ≥1 aberration in 89%; when adding cytogenetic data, this frequency increased to 98%. Uniparental isodisomies (UPIDs) were detected in 13% and copy number aberrations (CNAs) in 63% (median 2/case); three UPIDs and 22 CNAs were recurrent. Twenty‐two genes were targeted by focal CNAs, including AEBP2 and PHF6 deletions and genes involved in AML‐associated gene fusions. Deep sequencing identified mutations in 65% of cases (median 1/case). In total, 60 mutations were found in 30 genes, primarily those encoding signalling proteins (47%), transcription factors (25%), or epigenetic modifiers (13%). Twelve genes (BCOR, CEBPA, FLT3, GATA1, KIT, KRAS, NOTCH1, NPM1, NRAS, PTPN11, SMC3 and TP53) were recurrently mutated. We conclude that SNP‐A and deep sequencing analyses complement the cytogenetic diagnosis of paediatric AML.
Trends in primary central nervous system lymphoma incidence and survival in the U.S.
Authors: Shiels Meredith S. , Pfeiffer Ruth M. , Besson Caroline , Clarke Christina A. , Morton Lindsay M. , Nogueira Leticia , Pawlish Karen , Yanik Elizabeth L. , Suneja Gita , Engels Eric A.
Published: March 2016

It is suspected that primary central nervous system lymphoma (PCNSL) rates are increasing among immunocompetent people. We estimated PCNSL trends in incidence and survival among immunocompetent persons by excluding cases among human immunodeficiency virus (HIV)‐infected persons and transplant recipients. PCNSL data were derived from 10 Surveillance, Epidemiology and End Results (SEER) cancer registries (1992–2011). HIV‐infected cases had reported HIV infection or death due to HIV. Transplant recipient cases were estimated from the Transplant Cancer Match Study. We estimated PCNSL trends overall and among immunocompetent individuals, and survival by HIV status. A total of 4158 PCNSLs were diagnosed (36% HIV‐infected; 0·9% transplant recipients). HIV prevalence in PCNSL cases declined from 64·1% (1992–1996) to 12·7% (2007–2011), while the prevalence of transplant recipients remained low. General population PCNSL rates were strongly influenced by immunosuppressed cases, particularly in 20–39 year‐old men. Among immunocompetent people, PCNSL rates in men and women aged 65+ years increased significantly (1·7% and 1·6%/year), but remained stable in other age groups. Five‐year survival was poor, particularly among HIV‐infected cases (9·0%). Among HIV‐uninfected cases, 5‐year survival increased from 19·1% (1992–1994) to 30·1% (2004–2006). In summary, PCNSL rates have increased among immunocompetent elderly adults, but not in younger individuals. Survival remains poor for both HIV‐infected and HIV‐uninfected PCNSL patients.
Novel application assigned to toluquinol: inhibition of lymphangiogenesis by interfering with VEGF‐C/VEGFR‐3 signalling pathway
Authors: García‐Caballero M , Blacher S , Paupert J , Quesada A R , Medina M A , Noël A
Published: March 2016

Background and Purpose

Lymphangiogenesis is an important biological process associated with the pathogenesis of several diseases, including metastatic dissemination, graft rejection, lymphoedema and other inflammatory disorders. The development of new drugs that block lymphangiogenesis has become a promising therapeutic strategy. In this study, we investigated the ability of toluquinol, a 2‐methyl‐hydroquinone isolated from the culture broth of the marine fungus Penicillium sp. HL‐85‐ALS5‐R004, to inhibit lymphangiogenesis in vitro, ex vivo and in vivo.

Experimental Approach

We used human lymphatic endothelial cells (LECs) to analyse the effect of toluquinol in 2D and 3D in vitro cultures and in the ex vivo mouse lymphatic ring assay. For in vivo approaches, the transgenic Fli1:eGFPy1 zebrafish, mouse ear sponges and cornea models were used. Western blotting and apoptosis analyses were carried out to search for drug targets.

Key Results

Toluquinol inhibited LEC proliferation, migration, tubulogenesis and sprouting of new lymphatic vessels. Furthermore, toluquinol induced apoptosis of LECs after 14 h of treatment in vitro, blocked the development of the thoracic duct in zebrafish and reduced the VEGF‐C‐induced lymphatic vessel formation and corneal neovascularization in mice. Mechanistically, we demonstrated that this drug attenuates VEGF‐C‐induced VEGFR‐3 phosphorylation in a dose‐dependent manner and suppresses the phosphorylation of Akt and ERK1/2.

Conclusions and Implications

Based on these findings, we propose toluquinol as a new candidate with pharmacological potential for the treatment of lymphangiogenesis‐related pathologies. Notably, its ability to suppress corneal neovascularization paves the way for applications in vascular ocular pathologies.
Identification of anti‐cancer chemical compounds using Xenopus embryos
Authors: Tanaka Masamitsu , Kuriyama Sei , Itoh Go , Kohyama Aki , Iwabuchi Yoshiharu , Shibata Hiroyuki , Yashiro Masakazu , Aiba Namiko
Published: March 2016

Cancer tissues have biological characteristics similar to those observed in embryos during development. Many types of cancer cells acquire pro‐invasive ability through epithelial–mesenchymal transition (EMT). Similar processes (gastrulation and migration of cranial neural crest cells [CNCC]) are observed in the early stages of embryonic development in Xenopus during which cells that originate from epithelial sheets through EMT migrate to their final destinations. The present study examined Xenopus embryonic tissues to identify anti‐cancer compounds that prevent cancer invasion. From the initial test of known anti‐cancer drugs, AMD3100 (an inhibitor of CXCR4) and paclitaxel (a cytoskeletal drug targeting microtubules) effectively prevented migration during gastrulation or CNCC development. Blind‐screening of 100 synthesized chemical compounds was performed, and nine candidates that inhibited migration of these embryonic tissues without embryonic lethality were selected. Of these, C‐157 (an analog of podophyllotoxin) and D‐572 (which is an indole alkaroid) prevented cancer cell invasion through disruption of interphase microtubules. In addition, these compounds affected progression of mitotic phase and induced apoptosis of SAS oral cancer cells. SAS tumors were reduced in size after intratumoral injection of C‐157, and peritoneal dissemination of melanoma cells and intracranial invasion of glioma cells were inhibited by C‐157 and D‐572. When the other analogues of these chemicals were compared, those with subtle effect on embryos were not tumor suppressive. These results suggest that a novel chemical‐screening approach based on Xenopus embryos is an effective method for isolating anti‐cancer drugs and, in particular, targeting cancer cell invasion and proliferation.
Cultural Variation in Triadic Infant–Caregiver Object Exploration
Authors: Little Emily E. , Carver Leslie J. , Legare Cristine H.
Published: March 2016

Two studies examined the extent to which the type of triadic interaction pervasive in Western populations (i.e., shared visual attention and ostensive pedagogical cues) was representative of infant–caregiver object exploration in a non‐Western indigenous community. Caregivers in the United States and Vanuatu interacted with infants and a novel object for 3 min. In Study 1 (N = 116, Mage = 29.05), Ni‐Van caregivers used more physical triadic engagement and U.S. caregivers used more visual triadic engagement. In Study 2 (N = 80, Mage = 29.91), U.S. caregivers were more likely than Ni‐Van caregivers to transmit an action and to use visual cues while interacting with their child. These studies demonstrate that the Western model of early social learning is not universal.
Mending the Levee: How Supernaturally Anchored Conceptions of the Person Impact on Trauma Perception and Healing among Children (Cases from Madagascar and Nepal)
Authors: Evers Sandra , van der Brug Mienke , van Wesel Floryt , Krabbendam Lydia
Published: March 2016

When dealing with children and youth who experience distressing events, psychosocial diagnostics and healing programmes principally resort to biomedical models. Children are often viewed as individualised ‘victims’ suffering from trauma and ‘in need’ of outside help. Highlighting case studies from Madagascar and Nepal, this article argues that the biomedical approach to trauma would be strengthened by a concomitant analysis of social networks, including the perceived relations with the supernatural. The various tandems of family and kin relationships, the living and the dead, constitute not only a social ‘levee’ breached by distressing events, but also the locus around which social relations are rebuilt.
Household Consumption Distribution in Rural China: A Consistent Two‐Step Estimation
Authors: Tan Tao , Zhang Yanyuan , Wen Bo , Zhang Xinwen , Zhan Jintao
Published: March 2016

As China continues to experience rapid urbanization, understanding the distribution of rural household consumption presents important policy implications. We take a sample of 15,606 households from the National Rural Fixed Observation Point Survey conducted by China's Ministry of Agriculture in 2010. A consistent two‐step estimation based on the quadratic almost ideal demand system model is used to assess the distribution of living expenses across eight categories of goods and services. Results show that the price elasticity of food, clothing, and transportation and communication is relatively low, whereas that of durable goods, fuel, health and medicine, culture and education, and others is high. Demographic and regional variables also considerably affect living expenses. Our conclusions can serve as significant reference for evaluating changes in consumption structure and farmers’ welfare during the course of modernization in China. This type of analysis may also be conducted in other developing countries in general.

En raison de la forte accélération de l'urbanisation en Chine, une meilleure compréhension de la distribution des dépenses de consommation des ménages ruraux permettra d’élaborer de meilleures politiques. Dans la présente étude, nous avons constitué un échantillon de 15 606 ménages à partir de l'enquête National rural Fixed Observation Point réalisée par le ministère de l'Agriculture de la Chine en 2010. Nous avons appliqué une méthode d'estimation en deux étapes, fondée sur le modèle QUAIDS (système de demande presque parfait quadratique), pour évaluer la distribution des frais de subsistance dans huit catégories de biens et services. Les résultats de notre étude ont montré que l’élasticité‐prix des aliments, de l'habillement, du transport et des communications est relativement faible, tandis que celle des biens durables, du carburant, des soins de santé et des médicaments, de la culture et de l’éducation, entre autres, est élevée. Les variables démographiques et régionales ont également un impact considérable sur le niveau des dépenses. Les conclusions de notre étude peuvent servir de référence pour évaluer les changements qui touchent la structure de la consommation et le bien‐être des agriculteurs durant la modernisation de la Chine. Ce genre d'analyse peut également être appliqué à d'autres pays en développement.
Targeting Nicotinamide Phosphoribosyltransferase as a Potential Therapeutic Strategy to Restore Adult Neurogenesis
Authors: Wang Shu‐Na , Xu Tian‐Ying , Li Wen‐Lin , Miao Chao‐Yu
Published: March 2016

Adult neurogenesis is the process of generating new neurons throughout life in the olfactory bulb and hippocampus of most mammalian species, which is closely related to aging and disease. Nicotinamide phosphoribosyltransferase (NAMPT), also an adipokine known as visfatin, is the rate‐limiting enzyme for mammalian nicotinamide adenine dinucleotide (NAD) salvage synthesis by generating nicotinamide mononucleotide (NMN) from nicotinamide. Recent findings from our laboratory and other laboratories have provided much evidence that NAMPT might serve as a therapeutic target to restore adult neurogenesis. NAMPT‐mediated NAD biosynthesis in neural stem/progenitor cells is important for their proliferation, self‐renewal, and formation of oligodendrocytes in vivo and in vitro. Therapeutic interventions by the administration of NMN, NAD, or recombinant NAMPT are effective for restoring adult neurogenesis in several neurological diseases. We summarize adult neurogenesis in aging, ischemic stroke, traumatic brain injury, and neurodegenerative disease and review the advances of targeting NAMPT in restoring neurogenesis. Specifically, we provide emphasis on the P7C3 family, a class of proneurogenic compounds that are potential NAMPT activators, which might shed light on future drug development in neurogenesis restoration.
Fine needle aspiration cytology aided diagnosis of chordoma at an unusual site
Authors: Das S. , Dalal B. S. , Mukhopadhyay D. , Chatterjee U. , Datta C. , Chaudhuri M. K.
Published: March 2016

This correspondence discusses the cytological features of chordoma and its differential diagnosis.
Cytopathological features of pilomyxoid astrocytoma: a case report
Authors: Homma T. , Seki T. , Suzuki A. , Ohta T. , Maebayashi T. , Yoshino A. , Kusumi Y. , Sugitani M.
Published: March 2016

This is a case report concerning a Pilomyxoid Astrocytoma (PMA) occuring in a 4 month‐old child in the right temporal/suprasellar region of the brain. It was resected twice, the first time when the tumor was discovered and the second time four years later after recurrence as pilocytic astrocytoma (PA). Cytological features of PMA have been only rarely reported. Furthermore the authors have tried to discuss the evolution of a PMA to a PA illustrating the rare circumstances in which a tumor with a bad prognosis may evolve in a tumor with a better one.
Multicenter randomized controlled study to assess the effect of prophylactic clipping on post‐polypectomy delayed bleeding
Authors: Matsumoto Mio , Kato Mototsugu , Oba Koji , Abiko Satoshi , Tsuda Momoko , Miyamoto Shuichi , Mizushima Takeshi , Ono Masayoshi , Omori Saori , Takahashi Masakazu , Ono Shoko , Mabe Katsuhiro , Nakagawa Manabu , Nakagawa Soichi , Kudo Takahiko , Shimizu Yuichi , Sakamoto Naoya
Published: March 2016

Background and Aim

Prophylactic clipping has been widely used to prevent post‐procedural bleeding in colon polypctomy. However, its efficiency has not been confirmed and there is no consensus on the usefulness of prophylactic clipping. The aim of the present study was to evaluate the preventive effect of prophylactic clipping on post‐polypectomy bleeding.

Methods

A multicenter randomized controlled study was conducted from January 2012 to July 2013 in Japan. Patients who had polyps <2 cm in diameter were divided into a clipping group and a non‐clipping group by cluster randomization. After endoscopic polypectomy, patients allocated to the clipping group underwent prophylactic clipping, whereas the procedure was completed without clipping in patients allocated to the non‐clipping group. Occurrence of post‐polypectomy bleeding was compared between the two groups.

Results

Seven hospitals participated in this study. A total of 3365 polyps in 1499 patients were evaluated. The clipping group consisted of 1636 polyps in 752 patients, and the non‐clipping group consisted of 1729 polyps in 747 patients. Post‐polypectomy bleeding occurred in 1.10% (18/1636) of the cases in the clipping group, and in 0.87% (15/1729) of those in the non‐clipping group. The difference was –0.22% (95% confidence interval [CI]: –0.96, 0.53). Upper limit of the 95% CI was lower than the non‐inferiority margin (1.5%), and we could thus prove non‐inferiority of non‐clipping against clipping.

Conclusion

Prophylactic clipping is not necessary to prevent post‐polypectomy bleeding for polyps <2 cm in diameter.
Does Left Ventricular Geometric Patterns Impact Right Atrial Phasic Function? Findings from the Hypertensive Population
Authors: Tadic Marijana , Cuspidi Cesare , Kocijancic Vesna , Celic Vera , Vukomanovic Vladan
Published: March 2016

Objective

The aim of the study was to evaluate right atrial (RA) phasic function in hypertensive patients with different left ventricular (LV) geometric patterns by using two‐dimensional (2DE) and three‐dimensional (3DE) echocardiography.

Methods

This cross‐sectional study involved 177 hypertensive patients who underwent 2DE and 3DE examination. The updated criteria of LV geometry that included LV mass index, LV end‐diastolic diameter, and relative wall thickness were applied. Using this classification, patients were separated into six groups: normal geometry, concentric remodeling, eccentric nondilated LV hypertrophy (LVH), concentric LVH, dilated LVH, and concentric–dilated LVH.

Results

Two‐dimensional echocardiography and 3DE RA volumes were significantly higher in concentric and dilated LVH than in other LV geometric types. RA reservoir function, estimated by total 2DE and 3DE RA emptying fraction (EF), was decreased in subjects with dilated LVH compared with normal geometric and concentric LV remodeling patterns. RA conduit function assessed with 2DE and 3DE RA passive EF, gradually reduced from normal LV geometry to dilated LVH. RA pump function was increased in patients with concentric and dilated LVH than in subjects with normal LV geometry and concentric remodeling. 2DE strain analysis confirmed these findings about RA phasic function. Concentric LVH and dilated LVH were associated with RA enlargement and dysfunction irrespectively of main demographic and clinical parameters.

Conclusion

Left ventricular geometric patterns have significant impact on RA phasic function in hypertensive patients. Concentric and dilated LVH patterns have the most prominent negative effect on RA morphological and functional remodeling.
Sfrp5 associates with beta‐cell function in humans
Authors: Carstensen‐Kirberg Maren , Hatziagelaki Erifili , Tsiavou Anastasia , Chounta Athina , Nowotny Peter , Pacini Giovanni , Dimitriadis George , Roden Michael , Herder Christian
Published: March 2016

Background

Secreted frizzled‐related protein (Sfrp)5 improves insulin sensitivity, but impairs beta‐cell function in rodents. However, the relationship between Sfrp5, insulin sensitivity and secretion in humans is currently unclear. Therefore, the aim of the study was to characterize the associations between serum Sfrp5 and indices of insulin sensitivity and beta‐cell function from dynamic measurements using oral glucose tolerance tests (OGTT) in humans.

Material and methods

This study enrolled 194 individuals with nonalcoholic fatty liver disease (NAFLD), who were diagnosed based on ultrasound and liver transaminases and underwent a frequent sampling 75‐g OGTT. Fasting serum Sfrp5 was measured by ELISA. Associations were assessed with several indices of insulin sensitivity and beta‐cell function derived from glucose, insulin and C‐peptide concentrations during the OGTT.

Results

Circulating Sfrp5 associated inversely with the insulinogenic index based on C‐peptide (rs = −0·244, P = 0·001), but not with the insulinogenic index based on insulin levels (rs = −0·007, P = 0·926) after adjustment for age, sex and body mass index. Sfrp5 inversely correlated only with QUICKI as a marker of insulin sensitivity in the model adjusted for age and sex (rs = −0·149, P = 0·039). These associations were not influenced by the additional adjustment for hepatic steatosis index.

Conclusions

The inverse association of serum Sfrp5 with beta‐cell function suggests a detrimental role of Sfrp5 for insulin secretion also in humans. The severity of NAFLD does not appear to affect this relationship. The weak association between serum Sfrp5 and insulin sensitivity was partially explained by body mass.
Sarcopenia: Prevalence and associated factors based on different suggested definitions in community‐dwelling older adults
Authors: Kim Hunkyung , Hirano Hirohiko , Edahiro Ayako , Ohara Yuki , Watanabe Yutaka , Kojima Narumi , Kim Miji , Hosoi Erika , Yoshida Yuko , Yoshida Hideyo , Shinkai Shoji
Published: March 2016

The age‐related loss of muscle mass and/or strength and performance, sarcopenia, has been associated with geriatric syndromes, morbidity and mortality. Although sarcopenia has been researched for many years, currently there is a lack of consensus on its definition. Some studies define sarcopenia as low muscle mass alone, whereas other studies have recently combined low muscle mass, strength and physical performance suggested by the European Working Group on Sarcopenia in Older People, as well as the Asian Working Group for Sarcopenia. The arbitrary use of various available sarcopenia definitions within the literature can cause discrepancies in the prevalence and associated risk factors. The application of population‐specific cut‐off values in any sample population can be problematic, particularly among different ethnicities. Using commonly used cut‐off points to define sarcopenia, including solely muscle mass and combined definitions, on a community‐dwelling elderly Japanese population, the prevalence of sarcopenia ranged from 2.5 to 28.0% in men and 2.3 to 11.7% in women, with muscle mass measured by dual‐energy X‐ray absorptiometry, and 7.1–98.0% in men and 19.8–88.0% in women measured by bioelectrical impedance analysis. Body mass index was the most prominent related factor for sarcopenia across the definitions in this Japanese sample. However, other associated hematological and chronic condition factors varied depending on the definition. Geriatr Gerontol Int 2016; 16 (Suppl. 1): 110–122.
Secreted growth differentiation factor 15 as a potential biomarker for mitochondrial dysfunctions in aging and age‐related disorders
Authors: Fujita Yasunori , Taniguchi Yu , Shinkai Shoji , Tanaka Masashi , Ito Masafumi
Published: March 2016

We and other have recently shown that growth differentiation factor 15 (GDF15) is a useful diagnostic marker for mitochondrial diseases, which are inherited disorders caused by mitochondrial or nuclear genomic mutations that lead to impaired energy production. As the primary cause of mitochondrial diseases is mitochondrial dysfunction, the blood level of GDF15 might reflect mitochondrial function in patients, and thus could be a marker for mitochondrial dysfunction. GDF15 has been implicated in aging and various age‐related disorders, such as cardiovascular diseases and diabetes, the blood level of which is reportedly elevated in older adults as well as in patients. Although GDF15 might be induced as a result of various cellular stresses and dysfunctions, it would also be possible that the blood GDF15 level reflects at least in part mitochondrial dysfunction in aging and age‐related disorders. In the present review, we summarized the current literature regarding GDF15 in aging and age‐related disorders from the perspective of biomarkers, with a particular focus on mitochondrial dysfunction. Geriatr Gerontol Int 2016; 16 (Suppl. 1): 17–29.