bluuebunny/crossref_metadata_2025 huggingface dataset:
Adults with learning disabilities experiences of using community dental services: Service user and carer perspectives
Authors: Lees Carolyn , Poole Helen , Brennan Michelle , Irvine Fiona
Published: January 2017

Accessible summary

The government and other organisations say that improving health care is important for people with learning disabilities.

We asked people with learning disabilities and the people who look after them what it was like for them when they went to the dentist.

Those we asked said that when they went to the dentist, they knew that those they saw knew about looking after their teeth.

Some of those we talked to though said that certain things needed to be better.

Background

The government alongside other health and social care organisation have identified the need to improve the care provided for people with learning disabilities.

Materials and Methods

This service evaluation aimed to explore the experiences of people with learning disabilities and their carers who accessed community dental services using a qualitative research design. Adults with learning disabilities (n = 4) and their carers (n = 6) took part in one to one, face to face semi structured interviews.

Results and Discussion

Generally, participants were satisfied with community dental services and in particular valued the skills and the competence of practitioners. However, when dissatisfaction was expressed this was generally as a result of poor communication and the transition from child to adult dental services.

Conclusions

A number of recommendations are identified and discussed in relation to engagement with adults with learning disabilities and their carers in the development and delivery of community dental services.
Predictive and prognostic role of serum neopterin and tryptophan breakdown in prostate cancer
Authors: Pichler Renate , Fritz Josef , Heidegger Isabel , Steiner Eberhard , Culig Zoran , Klocker Helmut , Fuchs Dietmar
Published: January 2017

The γ‐interferon‐induced enzymes indoleamine 2,3‐dioxygenase and GTP‐cyclohydrolase are key players in tumor immune escape mechanisms. We quantified serum levels of neopterin and tryptophan breakdown (tryptophan, kynurenine, and kynurenine‐to‐tryptophan ratio) in addition to prostate‐specific antigen (PSA) in newly diagnosed prostate cancer (PCa) patients (n = 100) before radical prostatectomy (RP) as well as at time of biochemical recurrence (BCR) after RP (n = 50) in comparison to healthy men (n = 49). Effects of biomarkers on the risk of PCa diagnosis on transrectal biopsy, worse histopathological characteristics of the RP specimens, and cancer‐specific survival (CSS) after BCR were investigated. Neopterin (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.08–5.61; P = 0.032) and kynurenine (HR, 2.93; 95% CI, 1.26–6.79; P = 0.012) levels were univariately associated with CSS. When adjusted for other biomarkers, only neopterin remained an independent predictor of CSS (HR, 2.56; 95% CI, 1.07–6.12; P = 0.035). Only PSA was associated with an increased risk of PCa diagnosis on biopsy, univariately (odds ratio, 3.14; 95% CI, 1.68–5.88; P < 0.001) as well when adjusted for other biomarkers (odds ratio, 3.29; 95% CI, 1.70–6.35; P < 0.001). Moreover, only preoperative PSA was able to predict positive surgical margin (area under the receiver operating characteristic curve [AUC] = 0.71; 95% CI, 0.59–0.82; P = 0.001), higher Gleason score (AUC = 0.75; 95% CI, 0.66–0.85; P < 0.001) and extraprostatic involvement (AUC = 0.79; 95% CI, 0.69–0.88; P < 0.001) at RP specimens, respectively. Although serum neopterin and tryptophan breakdown cannot be considered as biomarkers in detecting PCa or in predicting worse final pathological findings, neopterin levels are useful for stratifying patients into different prognostic groups after BCR.
Effects of liraglutide on cardiovascular risk biomarkers in patients with type 2 diabetes and albuminuria: A sub‐analysis of a randomized, placebo‐controlled, double‐blind, crossover trial
Authors: von Scholten Bernt Johan , Persson Frederik , Rosenlund Signe , Eugen‐Olsen Jesper , Pielak Tomasz , Faber Jens , Hansen Tine W. , Rossing Peter
Published: January 2017

We assessed the effects of liraglutide treatment on five cardiovascular risk biomarkers, reflecting different pathophysiology: tumour necrosis factor (TNF)‐α; soluble urokinase plasminogen activator receptor (suPAR); mid‐regional pro‐adrenomedullin (MR‐proADM); mid‐regional pro‐atrial natriuretic peptide (MR‐proANP); and copeptin, in people with type 2 diabetes with albuminuria. In a randomized, double‐blind, placebo‐controlled, crossover trial we enrolled people with type 2 diabetes and persistent albuminuria (urinary albumin‐to‐creatinine ratio [UACR] >30 mg/g) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. Participants received liraglutide (1.8 mg/d) and matched placebo for 12 weeks, in random order. The primary endpoint was change in albuminuria; this was a prespecified sub‐study. A total of 32 participants were randomized, of whom 27 completed the study. TNF‐α level was 12% (95% confidence interval [CI] 3; 20) lower after liraglutide treatment compared with placebo (P = .012); MR‐proADM level was 4% (95% CI 0; 8) lower after liraglutide treatment compared with placebo (P = .038), and MR‐proANP level was 13% (95% CI 4; 21) lower after liraglutide treatment compared with placebo (P = .006). In the present study, we showed anti‐inflammatory effects of liraglutide treatment, reflected in reductions in levels of TNF‐α and MR‐proADM, while the reduction in MR‐proANP levels may represent a clinically relevant benefit with regard to heart failure.
Children's work and children's well‐being: Implications for policy
Authors: Aufseeser Dena , Bourdillon Michael , Carothers Richard , Lecoufle Olivia
Published: January 2017

This article argues for holistic consideration of children's work. Dominant discourse on “child labour” attends only to dangers of children's work, leading to policies that damage some children's chances for development. Far from being universally negative in children's lives, appropriate work contributes to their well‐being and development, and to transitions to adulthood. Children's work can convey benefits for sustenance and quality of life, provide learning to complement and support school, offer psycho‐social benefits, particularly in building self‐esteem, and help develop social relations and responsibility. These benefits are especially critical for marginalized children. Common policies of abolishing child labour based on age of employment rather than potential harm deny such benefits to younger children.
Protective effect of N,N’‐dimethylthiourea against stress‐induced gastric mucosal lesions in rats
Authors: Ohta Yoshiji , Yashiro Koji , Kobayashi Takashi , Inui Kazuo , Yoshino Junji
Published: January 2017

In the present study, we examined the protective effect of N,N’‐dimethylthiourea (DMTU), a scavenger of hydroxyl radical (), against water‐immersion restraint stress (WIRS)‐induced gastric mucosal lesions in rats. When male Wistar rats fasted for 24 h were exposed to WIRS for 3 h, gastric mucosal lesions occurred with increases in the levels of gastric mucosal myeloperoxidase (MPO), an index of tissue neutrophil infiltration, pro‐inflammatory cytokines (tumor necrosis factor alpha and interleukin 1beta), lipid peroxide (LPO), and nitrite/nitrate (NOx), an index of nitric oxide synthesis, and decreases in the levels of gastric mucosal nonprotein SH and vitamin C and gastric adherent mucus. DMTU (1, 2.5, or 5 mmol/kg) administered orally at 0.5 h before the onset of WIRS reduced the severity of gastric mucosal lesions with attenuation of the changes in the levels of gastric mucosal MPO, pro‐inflammatory cytokines, LPO, NOx, nonprotein SH, and vitamin C and gastric adherent mucus found at 3 h after the onset of WIRS in a dose‐dependent manner. Serum levels of corticosterone and glucose, which are indices of stress responses, increased in rats exposed to WIRS for 3 h, but DMTU pre‐administered at any dose had no effect on these increases. These results indicate that DMTU protects against WIRS‐induced gastric mucosal lesions in rats by exerting its antioxidant action including scavenging and its anti‐inflammatory action without affecting the stress response.
Enhanced transient receptor potential channel‐mediated Ca2+ influx in the cells with phospholipase C‐δ1 overexpression: its possible role in coronary artery spasm
Authors: Murakami Kazuo , Osanai Tomohiro , Tanaka Makoto , Nishizaki Kimitaka , Kinjo Takahiko , Tanno Tomohiro , Ishida Yuji , Suzuki Akiko , Endo Tomohide , Tomita Hirofumi , Okumura Ken
Published: January 2017

We reported that coronary spasm was induced in the transgenic mice with the increased phospholipase C (PLC)‐δ1 activity. We investigated the effect of enhanced PLC‐δ1 on Ca2+ influx and its underlying mechanisms. We used human embryonic kidney (HEK)‐293 and coronary arteries smooth muscle cells (CASMC). Intracellular free Ca2+ concentration ([Ca2+]i; nm) was measured by fura‐2, and Ca2+ influx was evaluated by the increase in [Ca2+]i after addition of extracellular Ca2+. Acetylcholine (ACh) was used to induce Ca2+ influx. ACh‐induced peak Ca2+ influx was 19 ± 3 in control HEK‐293 cells and 71 ± 8 in the cells with PLC‐δ1 overexpression (P < 0.05 between two groups). Nifedipine partially suppressed this Ca2+ influx, whereas either 2‐APB or knockdown of classical transient receptor potential channel 6 (TRPC6) blocked this Ca2+ influx. In the human CASMC, ACh‐induced peak Ca2+ influx was 29 ± 6 in the control and was increased to 45 ± 16 by PLC‐δ1 overexpression (P < 0.05). Like HEK‐293 cells, pretreatment with nifedipine partially suppressed Ca2+ influx, whereas either 2‐APB or knockdown of TRPC6 blocked it. ACh‐induced Ca2+ influx was enhanced by PLC‐δ1 overexpression, and was blocked partially by nifedipine and completely by 2‐APB. TRPC‐mediated Ca2+ influx may be related to the enhanced Ca2+ influx in PLC‐δ1 overexpression.
Structure of the Arabidopsis thaliana NADPH‐cytochrome P450 reductase 2 (ATR2) provides insight into its function
Authors: Niu Guoqi , Zhao Shun , Wang Lei , Dong Wei , Liu Lin , He Yikun
Published: January 2017

Members of the cytochrome P450 family catalyze a variety of mono‐oxygenase reactions, and for the eukaryotic membrane‐bound members, NADPH is typically used as the reducing agent. The flavoprotein NADPH‐cytochrome P450 reductase (CPR) enables electron transfer from NADPH to cytochrome P450 via its flavin cofactors. ATR2 is one of the two authentic CPR genes in the genome of the model plant Arabidopsis thaliana, and its product has been physiologically and kinetically characterized. Here, we report the 2.3 Å structure of Arabidopsis thaliana NADPH‐cytochrome P450 reductase 2 (ATR2) and find that the position of the two flavin cofactors differs from that of other known CPR structures. Mutation of residues related to possible interflavin electron transfer retains the reductase activity of ATR2, which suggests a direct electron transfer pathway between the flavins. In contrast, mutation of a single residue (R708) mediating interdomain interaction abolishes this activity. Because this residue is only conserved in plant CPRs, we speculate a plant‐specific working mechanism as observed in ATR2.

Database

Atomic coordinates and structure factors of ATR2 are available in the Protein Data Bank under the accession code 5GXU.
Efficient synthesis of α‐galactosyl oligosaccharides using a mutant Bacteroides thetaiotaomicron retaining α‐galactosidase (BtGH97b)
Authors: Okuyama Masayuki , Matsunaga Kana , Watanabe Ken‐ichi , Yamashita Keitaro , Tagami Takayoshi , Kikuchi Asako , Ma Min , Klahan Patcharapa , Mori Haruhide , Yao Min , Kimura Atsuo
Published: January 2017

The preparation of a glycosynthase, a catalytic nucleophile mutant of a glycosidase, is a well‐established strategy for the effective synthesis of glycosidic linkages. However, glycosynthases derived from α‐glycosidases can give poor yields of desired products because they require generally unstable β‐glycosyl fluoride donors. Here, we investigate a transglycosylation catalyzed by a catalytic nucleophile mutant derived from a glycoside hydrolase family (GH) 97 α‐galactosidase, using more stable β‐galactosyl azide and α‐galactosyl fluoride donors. The mutant enzyme catalyzes the glycosynthase reaction using β‐galactosyl azide and α‐galactosyl transfer from α‐galactosyl fluoride with assistance of external anions. Formate was more effective at restoring transfer activity than azide. Kinetic analysis suggests that poor transglycosylation in the presence of the azide is because of low activity of the ternary complex between enzyme, β‐galactosyl azide and acceptor. A three‐dimensional structure of the mutant enzyme in complex with the transglycosylation product, β‐lactosyl α‐d‐galactoside, was solved to elucidate the ligand‐binding aspects of the α‐galactosidase. Subtle differences at the β→α loops 1, 2 and 3 of the catalytic TIM barrel of the α‐galactosidase from those of a homologous GH97 α‐glucoside hydrolase seem to be involved in substrate recognitions. In particular, the Trp residues in β→α loop 1 have separate roles. Trp312 of the α‐galactosidase appears to exclude the equatorial hydroxy group at C4 of glucosides, whereas the corresponding Trp residue in the α‐glucoside hydrolase makes a hydrogen bond with this hydroxy group. The mechanism of α‐galactoside recognition is conserved among GH27, 31, 36 and 97 α‐galactosidases.

Database

The atomic coordinates (code: 5E1Q) have been deposited in the Protein Data Bank.
Assessing the influence of gilthead sea bream escapees in landings of Mediterranean fisheries through a scale‐based methodology
Authors: Izquierdo‐Gómez D. , Arechavala‐Lopez P. , Bayle‐Sempere J. T. , Sánchez‐Jerez P.
Published: January 2017

Gilthead sea bream (Sparus aurata L.) aquaculture has rapidly spread around the Mediterranean Sea. Fish escapes from sea cages are one of the major problems for the industry and also represent a threat to the marine environment. Fishery catches are also influenced by escape events, being mirrored in increased landings of cultured species. However, within the Mediterranean, studies shedding light on the incidence of escaped individuals in fisheries landings are scarce. Firstly, the present study describes a simple scale‐examination methodology to distinguish escaped from wild S. aurata landed by coastal fisheries. Secondarily, the incidence of escapees is assessed within landings of the species in the western Mediterranean. The scale readings revealed a monthly incidence of escapees between 11.2 and 20.8%, representing 6.8% of the total income derived from these landings. Moreover, morphological differences between wild fish captured near and far from fish farms point towards escape events as a source of potential genetic admixture between cultured and wild genotypes. Socio‐economic and ecological implications of escapees are discussed, and a set of management guidelines proposed, to prevent and/or mitigate the negative influences of escaped fish on the ecosystem and traditional users of the coast such as fisheries.
Aquatic food‐web structure along a salinized dryland river
Authors: East Jessica L. , Wilcut Christopher , Pease Allison A.
Published: January 2017

Very little is known about the ecosystem impacts of river salinization despite expectations for global increases in salinization with growing water demand and climate change. In some rivers in the southwestern United States, salinization has occurred as a result of natural saline inputs exacerbated by flow alteration and other anthropogenic impacts. Salinization in the Pecos River has been linked to declines in fish diversity, but impacts on the structure of aquatic food webs have not been investigated.

We assessed variation in local food webs along the longitudinal gradient of the main stem Pecos River by estimating carbon sources, trophic positions and assemblage‐wide trophic structure for aquatic consumers at 12 sites using stable isotope analysis (δ13C and δ15N). Temporal variation across seasons was also examined for common fish species at a subset of sites.

Consumer richness, food‐chain length and assemblage‐wide niche breadth were inversely related to specific conductivity. Mixing models revealed differences in sources of dietary carbon supporting fish production along the longitudinal fluvial gradient, with a shift towards reliance on algal production in the salinized reaches of the river. Trophic niche breadth was greatest for assemblages in less degraded sites with higher fish species richness. Local food webs in salinized sites were dominated by euryhaline species and had shorter food chains and narrower assemblage‐wide niche breadths. Across seasons, δ13C and δ15N signatures remained fairly constant for five common fish species.

Our results suggest that salinization in portions of the Pecos River constrains the diversity of consumers and trophic resources in local food webs. Characterising changes in food‐web structure in relation to salinization and other environmental changes is important for habitat assessment, stream restoration and other conservation strategies.
Temporal variation in phytoplankton beta diversity patterns and metacommunity structures across subtropical reservoirs
Authors: Wojciechowski Juliana , Heino Jani , Bini Luis M. , Padial André A.
Published: January 2017

Analysing the beta diversity components and spatial patterns of species distribution may provide key insights into how local communities respond to human‐induced environmental changes. Indeed, analysing temporal variation in spatial patterns of species distribution may reveal trends of biotic homogenisation and its likely causes.

We used an eight‐year phytoplankton data set generated from to 17 reservoirs in Brazil to analyse the temporal variability in beta diversity and its turnover and nestedness components. This data set was also used to determine metacommunity structures across these subtropical reservoirs. We tested whether there was any long‐term temporal trend in beta diversity that might be indicative of biotic homogenisation or differentiation. We also tested how temporal variation was related to climatic conditions, environmental heterogeneity, productivity and cyanobacterial dominance. Lastly, we verified whether the phytoplankton metacommunity showed non‐random structure.

We did not find supporting evidence for biotic homogenisation among the reservoirs. Rather, we did find that nestedness decreased during the study. Environmental heterogeneity was the main variable positively related to phytoplankton beta diversity, while high ammonium concentration and cyanobacterial abundance were negatively correlated with spatial variation among the reservoirs. Despite the noticeable temporal variation in metacommunity structures, the phytoplankton species responded similar to latent environmental gradients. Clementsian patterns found mainly in fall and winter were consistent with differences in species composition between sites, reinforcing the role of environmental filtering in driving changes in these metacommunities.

Our results suggest that eutrophication control is essential to prevent biotic homogenisation, at least in our study system. We also highlight that metacommunity patterns detected in snapshot surveys should not be extrapolated temporally.
Yeasts for Global Happiness: report of the 14th International Congress on Yeasts (ICY14) held in Awaji Island
Authors: Watanabe Daisuke , Takagi Hiroshi
Published: January 2017

The 14th International Congress on Yeasts (ICY14) was held at Awaji Yumebutai International Conference Center (Awaji, Hyogo) in Japan from 11 to 15 September 2016. The main slogan of ICY14 was ‘Yeasts for Global Happiness’, which enabled us to acknowledge the high‐potential usefulness of yeasts contributing to the global happiness in terms of food/beverage, health/medicine and energy/environment industries, as well as to basic biosciences. In addition, two more concepts were introduced: ‘from Japan to the world’ and ‘from senior to junior’. As it was the first ICY meeting held in Japan or other Asian countries, ICY14 provided a good opportunity to widely spread the great achievements by Japanese and Asian yeast researchers, such as those by the 2016 Nobel Laureate Dr. Yoshinori Ohsumi, and also, to convey the fun and importance of yeasts to the next generation of researchers from Asia and all over the world. As a result, a total of 426 yeast lovers from 42 countries (225 overseas and 201 domestic participants) with different generations attended ICY14 to share the latest knowledge of a wide range of yeast research fields and to join active and constructive scientific discussions.
Incidence, clinicopathological features and fusion transcript landscape of translocation renal cell carcinomas
Authors: Classe Marion , Malouf Gabriel G , Su Xiaoping , Yao Hui , Thompson Erika J , Doss Denaha J , Grégoire Valérie , Lenobin Julien , Fantoni Jean‐Christophe , Sudour‐Bonnange Hélène , Khayat David , Aubert Sébastien , Tannir Nizar M , Leroy Xavier
Published: January 2017

Aims

Translocation renal cell carcinoma (tRCC) is a rare subtype of kidney tumour characterized by translocations involving the transcription factor TFE3 or TFEB. tRCC was introduced into the World Health Organization classification in 2004, but much is still unknown about the natural history, clinicopathological features and outcomes of the disease. The aim of this study was to describe the landscape of fusion transcript in a large single‐institution series of fluorescence in‐situ hybridization (FISH)‐confirmed tRCCs and then to compare it to morphological and clinical data.

Methods and results

Paired‐end RNA sequencing was performed within a prospective database of the Department of Pathology, Centre Hospitalier Régional Universitaire (Lille, France). The diagnosis of tRCC was confirmed by FISH. Among a total of 1130 identified renal cell carcinomas, 21 cases (1.9%) showed rearrangement of the TFE3 (n = 20) or (TFEB) (n = 1) gene. Median patient age was 31 years (range = 15–47), and the female‐to‐male ratio was 6:1. Five different TFE3 fusion transcripts were identified; the most frequent TFE3 partners were PRCC (n = 4) and SFPQ (n = 4). The other partners involved were ASPCR1 (n = 1) and MED15 (n = 1) genes as well as a novel TFE3 partner, GRIPAP1.

Conclusions

We identified a new fusion partner, GRIPAP1. The prognostic role of transcript type could not be determined because our number of cases was too small. Four patients (19%) died of the disease, all of which presented with a lymph node involvement at diagnosis. We confirm that tRCC can be an aggressive tumour, especially those of advanced clinical stage.
Lung cancer and socio‐economic status: inextricably linked to place of residence
Authors: Denton Eve J. , Hart David , Russell Prue A. , Wright Gavin , Conron Matthew
Published: January 2017

Background

The association between socio‐economic status (SES) and lung cancer is internationally established, but in Australia this relationship remains ill defined.

Aims

To examine the association between SES, place of residence and lung cancer outcomes in a large Australian cohort.

Methods

A total of 2369 consecutive lung cancer patients managed by St Vincent's Hospital lung multidisciplinary meeting between 2001 and 2014 were included. Postcode data stratified participants by Socio‐economic indexes for areas, a validated measure of SES, and by geographical location, an important socio‐economic factor in Australia.

Results

There was no difference between socio‐economic groups in age (68 years), sex (63% males) or presentation (75% symptomatic). Low socio‐economic patients had increased smoking rates and a trend towards less adenocarcinoma. More low SES patients were from rural locations, had a greater frequency of earlier stage disease and curative treatment with higher overall survival even after multivariate analysis. When stratified for SES, overall 5‐year survival was significantly better in the low SES group (33 vs 24%, n = 2275, P = 0.02), although stage‐stratified survival was similar in all socio‐economic groups.

Conclusions

Low SES patients were more frequently from rural locations and unexpectedly had earlier stage disease and higher overall survival. The excellent outcomes in rural and lower SES patients are reassuring, but suggest that there is a population of these patients with advanced lung cancer who are not referred for multidisciplinary care. Further studies are required to define this group better and determine the barriers to referral to improve overall lung cancer outcomes.
Urinary fluoride excretion after application of fluoride varnish and use of fluoride toothpaste in young children
Authors: Lockner Frida , Twetman Svante , Stecksén‐Blicks Christina
Published: January 2017

Background

The efficacy and safety of combined use of topical fluoride products are essential issues that must be monitored.

Aim

To assess urinary excretion of fluoride after application of two different dental varnishes containing 2.26% fluoride in 3‐ to 4‐year‐old children and to compare the levels with and without parallel use of fluoride toothpaste.

Design

Fifteen healthy children were enrolled to a randomized crossover trial that was performed in two parts: Part I with twice‐daily tooth brushing with fluoride toothpaste and Part II with twice‐daily brushing with a non‐fluoride toothpaste. After a 1‐week run‐in period, 0.1 mL of the two fluoride varnishes (Duraphat and Profluorid Varnish) was topically applied in a randomized order. Baseline and experimental urine was collected during 6‐h periods. The fluoride content was determined with an ion‐sensitive electrode.

Results

There was a statistically significant increase in the 6‐h fluoride excretion after application of both experimental varnishes, with and without parallel use of fluoride toothpaste (P < 0.01). When fluoridated toothpaste was used, the mean fluoride excretion was 0.20 mg/6 h after application of Duraphat and 0.29 mg/6 h after application of Profluorid Varnish (P = 0.18).

Conclusions

Topical applications of 0.1 mL of fluoride varnish significantly increased the 6‐h fluoride excretion. As some individuals displayed excretion levels exceeding the optimal fluoride exposure, a restricted use of fluoride toothpaste in connection with the varnish applications would decrease fluoride exposure.
Self‐administered health literacy instruments for people with diabetes: systematic review of measurement properties
Authors: Lee Eun‐Hyun , Kim Chun‐Ja , Lee Jiyeon , Moon Seung Hei
Published: January 2017

Aims

The aims of this study were to identify all available self‐administered instruments measuring health literacy in people with diabetes and to determine the current instrument that is the most appropriate for applying to this population in both practice and research.

Design

A systematic review of measurement properties.

Data sources

MEDLINE, EMBASE and CINAHL electronic databases from their inception up to 28 March 2016.

Review method

The methodological quality of each included study was assessed using the COnsensus‐based Standards for the selection of health Measurement INstruments checklist. The reported results for measurement properties in the studies were assessed according to Terwee's quality criteria.

Results

Thirteen self‐administered instruments measuring health literacy in people with diabetes were identified, of which six (44%) were diabetes‐specific instruments. The instruments that covered the broadest contents of health literacy were the Health Literacy Scale and Health Literacy Questionnaire. The (test–retest) reliability, measurement error and responsiveness were not evaluated for any instrument, while internal consistency and hypothesis testing validity were the most frequently assessed measurement properties.

Conclusions

With the current evidence, the Health Literacy Scale may be the most appropriate instrument for patients with diabetes in practice and research. However, the structural validity of this scale needs to be further established, particularly in other language versions. It is also recommended to use the Diabetes Numeracy Test‐15 along with the Health Literacy Scale to complement the lack of numeracy measures in the Health Literacy Scale.
Rare human leukocyte antigen genotype in two siblings with type 1 diabetes in a Japanese family clustered with type 1 diabetes
Authors: Ina Yujiro , Kawabata Yumiko , Sakamoto Ryuichi , Sekiguchi Naotaka , Ikegami Hiroshi
Published: January 2017

Multiplex families with type 1 diabetes are important for identification of rare variants that cannot be identified in case–control association studies. The very low incidence of type 1 diabetes in the Japanese population, however, makes identification of such families difficult. We identified a Japanese family in which three members developed type 1 diabetes, and studied the genotype of the human leukocyte antigen. All three members with type 1 diabetes had the DRB1*08:02‐DQB1*03:02 haplotype, which is specific to the Asian population and strongly susceptible for type 1 diabetes. In particular, a proband and his sister had the same genotype, DRB1*08:02‐DQB1*03:02/DRB1*08:02‐DQB1*03:02, which is extremely rare even in the Japanese population. Both parents also had DRB1*08:02‐DQB1*03:02, but in combination with different human leukocyte antigen haplotypes. Weakly susceptible DRB1*13:02‐DQB1*06:04 was present in the affected mother, and resistant DRB1*15:01‐DQB1*06:02 in the unaffected father. These data suggest DRB1*08:02‐DQB1*03:02 to be a contributing factor for familial clustering of type 1 diabetes in this family.
Effects of mineralocorticoid receptor antagonists on the progression of diabetic nephropathy
Authors: Sun Li‐Jing , Sun Yan‐Ni , Shan Jian‐Ping , Jiang Geng‐Ru
Published: January 2017

Aims/Introduction

We aimed to evaluate the potential benefits and adverse effects of adding a mineralocorticoid receptor antagonist (MRA) to angiotensin‐converting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB), as standard treatment in patients with diabetic nephropathy.

Materials and Methods

We scanned the Embase, PubMed and Cochrane Central Register of Controlled Trials databases for human clinical trials published in English until June 2016, evaluating renal outcomes in patients with diabetic nephropathy.

Results

A total of 18 randomized controlled trials involving 1,786 patients were included. Compared with ACEI/ARB alone, co‐administration of MRA and ACEI/ARB significantly reduced urinary albumin excretion and the urinary albumin–creatinine ratio (mean difference −69.38, 95% confidence intervals −103.53 to −35.22, P < 0.0001; mean difference −215.74, 95% confidence intervals −409.22 to −22.26, P = 0.03, respectively). A decrease of blood pressure was also found in the co‐administration of MRA and ACEI/ARB groups. However, we did not observe any improvement in the glomerular filtration rate. There was a significant increase in the risk of hyperkalemia on the addition of MRA to ACEI/ARB treatment (relative risk 3.74, 95% confidence intervals 2.30–6.09, P < 0.00001).

Conclusions

These findings suggest that co‐administration of MRA and ACEI/ARB has beneficial effects on renal outcomes with increasing the incidence of hyperkalemia.
iDermatoPath – a novel software tool for mitosis detection in H&E‐stained tissue sections of malignant melanoma
Authors: Andres C. , Andres‐Belloni B. , Hein R. , Biedermann T. , Schäpe A. , Brieu N. , Schönmeyer R. , Yigitsoy M. , Ring J. , Schmidt G. , Harder N.
Published: January 2017

Background

Malignant Melanoma (MM) is characterized by a growing incidence and a high malignant potential. Besides well‐defined prognostic factors such as tumour thickness and ulceration, the Mitotic Rate (MR) was included in the AJCC recommendations for diagnosis and treatment of MM. In daily routine, the identification of a single mitosis can be difficult on haematoxylin and eosin slides alone. Several studies showed a big inter‐ and intra‐individual variability in detecting the MR in MM even by very experienced investigators, thus raising the question for a computer‐assisted method.

Objective

The objective was to develop a software system for mitosis detection in MM on H&E slides based on machine learning for diagnostic support.

Methods

We developed a computer‐aided staging support system based on image analysis and machine learning on the basis of 59 MM specimens. Our approach automatically detects tumour regions, identifies mitotic nuclei and classifies them with respect to their diagnostic relevance. A convenient user interface enables the investigator to browse through the proposed mitoses for fast and efficient diagnosing.

Results

A quantitative evaluation on manually labelled ground truth data revealed that the tumour region detection yields a medium spatial overlap index (dice coefficient) of 0.72. For the mitosis detection, we obtained high accuracies of above 83%.

Conclusion

On the technical side, the developed iDermatoPath software tool provides a novel approach for mitosis detection in MM, which can be further improved using more training data such as dermatopathologist annotations. On the practical side, a first evaluation of the clinical utility was positive, albeit this approach provides most benefit for difficult cases in a research setting. Assuming all slides to be digitally processed and reported in the near future, this method could become a helpful additional tool for the pathologist.
Validation of daily increment deposition and early growth of mud carp Cirrhinus molitorella
Authors: Huang Y. , Chen F. , Tang W. , Lai Z. , Li X.
Published: January 2017

In this study, laboratory reared Cirrhinus molitorella from hatching through to the juvenile stage were used to validate daily increment deposition. Lapilli were suitable for ageing C. molitorella. The slope of the linear relationships between increment counts and age was not significantly different from 1 (n = 258, P > 0·05), indicating that growth increments are deposited daily. The first increment following the first‐feeding check formed 3 days post hatch (dph). One hundred and twenty‐three juveniles, ranging from 36·4 to 84·7 mm in body length (LB), were collected in the Pear River estuary from July to January in both 2014 and 2015 and used to estimate growth rate. The core in the lapillus, consisting of a single primordium, a diffuse area and the first‐feeding band, was followed by 20 narrow and poorly contrasted daily increments. Thereafter, increments were wide and well‐defined, and, finally became less distinct, but still homogenous after c. 53 dph. The mean increment width increased to the 29th increment and stayed relatively constant up to the 35th increment and then, gradually declined to the edge of the otolith. Wild juveniles were aged from 69 to 178 dph and hatched from the 15 February to 2 September. Growth rate was estimated from the adjusted linear regression of LB on age: LB = 4·37 + 0·44A (r2 = 0·60), where A = age. The radius of the core and the regularity and resolution of the increments showed some differences between reared and wild fish. These results are of value for the further study of early life traits and recruitment of C. molitorella.
Lesser devil rays Mobula cf. hypostoma from Venezuela are almost twice their previously reported maximum size and may be a new sub‐species
Authors: Ehemann N. R. , González‐González L. V. , Trites A. W.
Published: January 2017

Three rays opportunistically obtained near Margarita Island, Venezuela, were identified as lesser devil rays Mobula cf. hypostoma, but their disc widths were between 207 and 230 cm, which is almost double the reported maximum disc width of 120 cm for this species. These morphometric data suggest that lesser devil rays are either larger than previously recognized or that these specimens belong to an unknown sub‐species of Mobula in the Caribbean Sea. Better data are needed to describe the distribution, phenotypic variation and population structure of this poorly known species.
Genetic Polymorphisms in Estrogen Metabolic Pathway Associated with Risks of Alzheimer's Disease: Evidence from a Southern Chinese Population
Authors: Chen Lu Hua , Fan Yan Hui , Kao Patrick Yu Ping , Ho Deborah Tip Yin , Ha Joyce Cheuk Tung , Chu Leung Wing , Song You‐Qiang
Published: January 2017

Objectives

To investigate whether genetic variations on the estrogen metabolic pathway would be associated with risk of Alzheimer's disease (AD).

Design

Cross‐sectional study.

Setting

Individuals were recruited at the Memory Clinic, Queen Mary Hospital, Hong Kong.

Participants

Chinese individuals with (n = 426) and without (n = 350) AD.

Measurements

All subjects underwent a standardized cognitive assessment and genotyping of four candidate genes on the estrogen metabolic pathway (estrogen receptor α gene (ESR1), estrogen receptor β gene (ESR2), cytochrome P450 19A1 gene (CYP19A1), cytochrome P450 11A1 gene (CYP11A1)).

Results

Apart from consistent results showing an association between apolipoprotein (APO)E and AD, strong evidence of disease associations were found for polymorphisms in ESR2 and CYP11A1 based on the entire data set. For ESR2, significant protective effects were found for A alleles of rs4986938 (permuted P = .02) and rs867443 (permuted P = .02). For CYP11A1, significant risk effects were found for G alleles of rs11638442 (permuted P = .03) and rs11632698 (permuted P = .03). Stratifying subjects according to APOE ε4 status, their genetic effects continued to be significant in the APOE ε4‐negative subgroup. Associations between CYP11A1 polymorphisms (rs2279357, rs2073475) and risk of AD were detected in women but not men. Further gene‐level analysis confirmed the above association between ESR2 and CYP11A1, and pathway‐level analysis highlighted the genetic effect of the estrogen metabolic pathway on disease susceptibility (permuted pathway‐level P = .03).

Conclusion

Consistent with previous biological findings for sex steroid hormones in the central nervous system, genetic alterations on the estrogen metabolic pathway were revealed in the Chinese population. Confirmation of these present findings in an independent population is warranted to elucidate disease pathogenesis and to explore the potential of hormone therapy in the treatment of AD.
Microdiamond on Åreskutan confirms regional UHP metamorphism in the Seve Nappe Complex of the Scandinavian Caledonides
Authors: Klonowska I. , Janák M. , Majka J. , Petrík I. , Froitzheim N. , Gee D. G. , Sasinková V.
Published: January 2017

Metamorphic diamond in crustal rocks provides important information on the deep subduction of continental crust. Here, we present a new occurrence of diamond within the Seve Nappe Complex (SNC) of the Scandinavian Caledonides, on Åreskutan in Jämtland County, Sweden. Microdiamond is found in situ as single and composite (diamond+carbonate) inclusions within garnet, in kyanite‐bearing paragneisses. The rocks preserve the primary peak pressure assemblage of Ca,Mg‐rich garnet+phengite+kyanite+rutile, with polycrystalline quartz surrounded by radial cracks indicating breakdown of coesite. Calculated P–T conditions for this stage are 830–840 °C and 4.1–4.2 GPa, in the diamond stability field. The ultrahigh‐pressure (UHP) assemblage has been variably overprinted under granulite facies conditions of 850–860 °C and 1.0–1.1 GPa, leading to formation of Ca,Mg‐poor garnet+biotite+plagioclase+K‐feldspar+sillimanite+ilmenite+quartz. This overprint was the result of nearly isothermal decompression, which is corroborated by Ti‐in‐quartz thermometry. Chemical Th–U–Pb dating of monazite yields ages between 445 and 435 Ma, which are interpreted to record post‐UHP exhumation of the diamond‐bearing rocks. The new discovery of microdiamond on Åreskutan, together with other evidence of ultrahigh‐pressure metamorphism (UHPM) within gneisses, eclogites and peridotites elsewhere in the SNC, provide compelling arguments for regional (at least 200 km along strike of the unit) UHPM of substantial parts of this far‐travelled allochthon. The occurrence of UHPM in both rheologically weak (gneisses) and strong lithologies (eclogites, peridotites) speaks against the presence of large tectonic overpressure during metamorphism.
Mapping the intermediate digestion phases of human healthy intestinal contents from distal ileum and caecum at fasted and fed state conditions
Authors: Tran Thuy , Fatouros Dimitrios G , Vertzoni Maria , Reppas Christos , Müllertz Anette
Published: January 2017

Objectives

To investigate at the ultrastructural level, the colloidal phases formed in the lumen of the distal ileum and caecum of healthy adults.

Methods

Cryogenic transmission electron microscopy (Cryo-TEM) was employed to image the intermediate colloidal phases of human intestinal contents collected from distal ileum and caecum of two healthy volunteers under fasted and fed state conditions.

Key findings

In samples collected both in the fasted and fed states, Cryo-TEM study revealed the presence of large spherical unilamellar and occasionally bi-lamellar and oligolamellar vesicles with diameters ranging from 50 to 200 nm for both volunteers in distal ileum and caecum. Bilayer fragments were frequently observed in caecal samples. Plate-like structures resembling the morphology of cholesterol plates were visualised in all samples. Elongated structures were observed in the fed state in distal ileum and caecum for both volunteers, whereas no micellar structures could be detected for all samples.

Conclusions

This study provides a framework for understanding the structure of colloidal phases, and it may assist in elucidating the role of dosing conditions on drug absorption from the distal ileum and caecum.
Limitations of polyethylene glycol-induced precipitation as predictive tool for protein solubility during formulation development
Authors: Hofmann Melanie , Winzer Matthias , Weber Christian , Gieseler Henning
Published: January 2017

Objective

Polyethylene glycol (PEG)-induced protein precipitation is often used to extrapolate apparent protein solubility at specific formulation compositions. The procedure was used for several fields of application such as protein crystal growth but also protein formulation development. Nevertheless, most studies focused on applicability in protein crystal growth. In contrast, this study focuses on applicability of PEG-induced precipitation during high-concentration protein formulation development.

Methods

In this study, solubility of three different model proteins was investigated over a broad range of pH. Solubility values predicted by PEG-induced precipitation were compared to real solubility behaviour determined by either turbidity or content measurements.

Key findings

Predicted solubility by PEG-induced precipitation was confirmed for an Fc fusion protein and a monoclonal antibody. In contrast, PEG-induced precipitation failed to predict solubility of a single-domain antibody construct. Applicability of PEG-induced precipitation as indicator of protein solubility during formulation development was found to be not valid for one of three model molecules.

Conclusions

Under certain conditions, PEG-induced protein precipitation is not valid for prediction of real protein solubility behaviour. The procedure should be used carefully as tool for formulation development, and the results obtained should be validated by additional investigations.
The Inevitability and Indeterminacy of Game-Theoretic Accounts of Legal Order
Authors: Levinson Daryl
Published: January 2017

How is legal order possible? Why do people comply with law when it prevents them from doing what they think best? Two important books show how these questions can—and from some methodological perspectives must—be answered in the form of game-theoretic accounts that show how legal compliance can be compatible with the broad self-interest of officials and citizens. Unfortunately, however, these books also serve to demonstrate that game-theoretic accounts along these lines lack the resources to explain how real-world legal systems emerge and evolve or the various institutional shapes these systems take. The fundamental limitation of game theory, in this context and more generally, is its inability to predict or explain the size and shape of cooperative equilibria.
Mechanism of type‐III protein secretion: Regulation of FlhA conformation by a functionally critical charged‐residue cluster
Authors: Erhardt Marc , Wheatley Paige , Kim Eun A , Hirano Takanori , Zhang Yang , Sarkar Mayukh K. , Hughes Kelly T. , Blair David F.
Published: January 2017

The bacterial flagellum contains a specialized secretion apparatus in its base that pumps certain protein subunits through the growing structure to their sites of installation beyond the membrane. A related apparatus functions in the injectisomes of gram‐negative pathogens to export virulence factors into host cells. This mode of protein export is termed type‐III secretion (T3S). Details of the T3S mechanism are unclear. It is energized by the proton gradient; here, a mutational approach was used to identify proton‐binding groups that might function in transport. Conserved proton‐binding residues in all the membrane components were tested. The results identify residues R147, R154 and D158 of FlhA as most critical. These lie in a small, well‐conserved cytoplasmic domain of FlhA, located between transmembrane segments 4 and 5. Two‐hybrid experiments demonstrate self‐interaction of the domain, and targeted cross‐linking indicates that it forms a multimeric array. A mutation that mimics protonation of the key acidic residue (D158N) was shown to trigger a global conformational change that affects the other, larger cytoplasmic domain that interacts with the export cargo. The results are discussed in the framework of a transport model based on proton‐actuated movements in the cytoplasmic domains of FlhA.
Extranational spaces and the disruption of national boundaries: Turkish immigrant media and claims against the state in 1980s West Germany
Authors: Foerster Amy , Miller Jennifer
Published: January 2017

After the 1980 coup that shook Turkey and almost twenty years after the bilateral ‘guest worker’ treaty shifted Germany's demographic make‐up, West German policy makers proposed increasingly restrictive regulations on the ‘guest workers’ who had heavily contributed to West Germany's economy. In this crucial historical moment, Turkish‐language newspapers, published in West Germany, created a politically motivated extranational public sphere in which they launched claims against both the West German and Turkish states. These claims shaped immigration and integration policy between the two countries, fostered diasporic activism and cross‐national religious and political organisations and gave rise to a variety of unexpected organisational outcomes that continue to impact both Germany and the Turkish Republic.