bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of diabetic retinopathy in Type 2 diabetes in developing and developed countries
Authors: Ruta L. M. , Magliano D. J. , LeMesurier R. , Taylor H. R. , Zimmet P. Z. , Shaw J. E. 
Published: January 2013

AbstractBackgroundAs the global prevalence of diabetes increases, so will the numbers of people with diabetic retinopathy. Our review aimed to provide a comprehensive picture of available studies of diabetic retinopathy and how prevalence varies around the developed and developing world.MethodsA detailed literature search using PubMed was undertaken. The following search term was used: ‘diabetic retinopathy AND prevalence’. The titles and abstracts of all publications identified by the search were reviewed and 492 studies were retrieved. Inclusion and exclusion criteria were applied.ResultsA total of 72 articles from 33 countries were included. There were only 26 population‐based studies using fundus photography (12 in developing countries), of which only 16 (eight in developing countries) were published since 2000. Prevalence estimates varied from as low as 10% to as high as 61% in persons with known diabetes and from 1.5 to 31% in newly diagnosed diabetes. Across all the studies, the median (interquartile range) prevalence of any diabetic retinopathy in known diabetes was 27.9% (22–37%) and 10.5% (6–16%) in newly diagnosed diabetes. Prevalence of diabetic retinopathy was higher in developing countries.ConclusionSignificant gaps exist in that reliable population‐based data from developing nations and indigenous populations in particular are lacking. Major differences in study characteristics and methodologies make comparisons very difficult. More research is required and study methodologies must be better standardized. This will provide important information for prevention and treatment strategies.
Lack of GPR40/FFAR1 does not induce diabetes even under insulin resistance condition
Authors: Matsuda‐Nagasumi K. , Takami‐Esaki R. , Iwachidow K. , Yasuhara Y. , Tanaka H. , Ogi K. , Nakata M. , Yano T. , Hinuma S. , Taketomi S. , Odaka H. , Kaisho Y. 
Published: January 2013

AimsG protein‐coupled receptor/free fatty acid receptor 1 (GPR40/FFAR1) regulates free fatty acid‐induced insulin secretion. This study has been performed to clarify whether or not loss of GPR40/FFAR1 function exacerbates diabetes, that is, whether GPR40 has an essential physiological role in the development of diabetes or not.MethodsWe generated GPR40/FFAR1 knockout (KO) mice and analysed their phenotypes in vitro and in vivo under the condition of dietary or genetically induced insulin resistance.ResultsGPR40/FFAR1 KO mice kept on a high‐fat diet became obese, developed glucose intolerance to a similar degree as GPR40/FFAR1 wild‐type (WT) mice. In addition, the phenotype of KO mice harbouring diabetogenic KK background genes showed glucose intolerance at a level similar to level for control KK mice. In both mouse models with insulin resistance, insulin secretion after oral glucose load and homeostasis model assessment‐insulin resistance (HOMA‐IR) did not change between GPR40/FFAR1 KO and WT mice. Although glucose‐induced insulin secretion under high palmitate concentration was significantly lower in KO than in WT islets, pancreatic insulin content and insulin secretion stimulated with glucose alone were not different between KO and WT mice.ConclusionsGPR40/FFAR1 has a major role in regulating fatty‐acid‐mediated insulin secretion, but the lack of GPR40/FFAR1 does not exacerbate glucose intolerance and insulin resistance induced by high‐fat diet or diabetogenic KK gene. Our findings indicate that loss of GPR40/FFAR1 function does not play an important role in inducing or exacerbating diabetes.
Interleukin‐17 enhances the production of interferon‐γ and tumour necrosis factor‐α by bone marrow T lymphocytes from patients with lower risk myelodysplastic syndromes
Authors: Zhang Zheng , Li Xiao , Guo Juan , Xu Feng , He Qi , Zhao Youshan , Yang Yujuan , Gu Shucheng , Zhang Yan , Wu Lingyun , Chang Chunkang 
Published: January 2013

AbstractIntroductionLower risk myelodysplastic syndromes (MDSs) are characterised by increased apoptosis of haematopoietic cells in the bone marrow (BM). The mechanism driving this excessive apoptosis involves multiple immune molecules, including inflammatory cytokines such as interferon‐γ (IFN‐γ), tumour necrosis factor‐α (TNF‐α) and interleukins (ILs). Interleukin‐17 (IL‐17) is the hallmark cytokine produced by CD4+ Th17 cells, and IL‐17 mediates activation of the adaptive T‐cell response inducing an inflammatory cytokine environment. However, little is known about the role of IL‐17 in MDS‐associated immune dysfunction.MethodsA total of 47 patients with myelodysplastic syndromes were enrolled in this study, and the levels of IL‐17 and IL‐17 receptor (IL‐17R) in BM mononuclear cells (BMNCs) were detected by real‐time polymerase chain reaction (RQ‐PCR) and enzyme‐linked immunosorbent assay (ELISA). Then, BMNCs were stimulated with recombinant human IL‐17 (rhIL‐17), and flow cytometry was used to analyse the production of IFN‐γ and TNF‐α by CD4+ and CD+ T lymphocytes from patients with lower‐risk MDS. Characterisation of IL‐17 expression in patients with the HLA‐DR15 allele or hypocellularity was also performed.ResultsmRNA levels for both IL‐17 and the IL‐17R subunits in BMNCs and for IL‐17 in the BM and plasma were higher in patients with lower‐risk MDS as compared to patients with higher‐risk MDS and normal controls. The production of IFN‐γ and TNF‐α by CD4+ and CD8+ T lymphocytes from patients with lower‐risk MDS could be enhanced by recombinant human IL‐17 (rhIL‐17) treatment. Furthermore, increased IL‐17 expression was associated with more severe anaemia in with patients with MDS.ConclusionElevated IL‐17 levels and IL‐17‐induced IFN‐γ and TNF‐α overproduction may be involved in the pathogenesis of lower risk MDS.
Prognostic significance of programmed cell death‐1‐positive cells in follicular lymphoma patients may alter in the rituximab era
Authors: Takahashi Hiroyuki , Tomita Naoto , Sakata Seiji , Tsuyama Naoko , Hashimoto Chizuko , Ohshima Rika , Matsuura Shiro , Ogawa Koji , Yamamoto Wataru , Kameda Yoichi , Enaka Makiko , Inayama Yoshiaki , Kasahara Masao , Takekawa Yoshinori , Onoda Noboru , Motomura Shigeki , Ishigatsubo Yoshiaki , Takeuchi Kengo 
Published: January 2013

AbstractProgrammed cell death‐1 (PD‐1) is involved in one of the inhibitory pathways of the B7‐cluster of differentiation (CD) 28 family; this pathway is known to be involved in the attenuation of T‐cell responses and promotion of T‐cell tolerance. PD‐1 is known to negatively regulate T‐cell receptor‐mediated proliferation and cytokine production, lead to alternation in the tumor microenvironment. Although several studies have shown that high levels of PD‐1‐positive cells in follicular lymphoma (FL) patients influence their prognosis, those studies included patients treated without rituximab, and the prognostic impact of PD‐1 positivity in the rituximab era (R‐era) has not yet been elucidated. We retrospectively studied 82 patients with FL uniformly treated with standard R‐CHOP therapy at six institutions between 2001 and 2009 (median follow‐up for survivors: 55 months). We also collected and examined biopsy specimens for diagnosis with respect to PD‐1 positivity. The PD‐1 positivity was significantly higher in male patients and patients with high beta‐2 microglobulin (B2M ≥ 3.0) (P = 0.03 and 0.003, respectively). Three‐year progression free survival (PFS) and overall survival (OS) were 60% and 86%, respectively. By univariate analysis, elevated LDH (P = 0.07) worsened PFS. Male gender (P = 0.03), high FLIPI score (P = 0.05), and high B2M levels (P = 0.08) worsened OS. Multivariate analysis detected no significant prognostic factors, including PD‐1 positivity. However, in male subgroup, high levels of PD‐1‐positive cells were found to be a prognostic factor for PFS. Addition of rituximab might have altered the prognostic impact of PD‐1‐positive cells.
Thirty‐year experience in preventing haemoglobinopathies in Greece: achievements and potentials for optimisation
Authors: Ladis Vassilis , Karagiorga‐Lagana Markissia , Tsatra Ioanna , Chouliaras Giorgos 
Published: January 2013

AbstractObjectivesBeta thalassaemia major (β‐TM) and sickle‐cell disease (SCD) are severe haemogobinopathies requiring life‐lasting, advanced medical management. In the Mediterranean region, both conditions occur with high frequency. We assessed the efficacy of the National Program for the Prevention of Haemoglobinopathies in Greece during the last 30 yrs.MethodsData of affected births between 01/01/1980 and 31/12/2009 were collected in a nationwide scale, and expected vs. observed rates of new births were calculated and compared. In a subpopulation of affected births of Greek origin, the causes for occurrence of the new affected birth were also collected and analysed.ResultsOverall, the reduction in new cases was 81.1% and 84.6% for β‐TM and SCD, respectively. For β‐TM, a constant declining trend was recorded over the 30‐yr period, whereas for SCD, a transient reversal was observed in the mid‐1990s probably due to the significant influx of immigrants of African origin. Programme failure was 2.2 times more common among new β‐TM births of Greek origin compared to new SCD cases (P < 0.001). Unawareness and parental choice were more frequent in SCD compared to β‐TM (unawareness: OR = 1.4, P = 0.05, parental choice: OR = 1.9, P = 0.01). The main cause for programme failure was carrier misidentification and incorrect genetic advice for β‐TM and SCD, respectively.ConclusionsThe β‐TM and SCD prevention programme in Greece has significantly reduced the numbers of new affected births. The outcomes could be optimised in groups of non‐Greek origin, in carrier identification and by offering specialised genetic counselling.
Attention deficit hyperactivity disorder and dental anxiety in adults: relationship with oral health
Authors: Carlsson Viktor , Hakeberg Magnus , Blomkvist Klas , Wide Boman Ulla 
Published: January 2013

The aim of the present study was to investigate the presence of attention deficit hyperactivity disorder (ADHD) in adult patients with severe dental anxiety. Specifically, we analysed the relationship among ADHD, oral health, and dental anxiety. The World Health Organization Adult ADHD Self‐Report Scale (ASRS) Screener was administered to a consecutive sample of patients referred to a dental fear research and treatment clinic. Patients completed questionnaires measuring dental anxiety (Dental Fear Survey) and self‐rated oral health, and underwent a full radiographic examination. Of the total sample (n = 110), 16% scored above the established ASRS cut‐off point, which is indicative of having ADHD. The ADHD group showed a higher level of dental anxiety and poorer self‐rated oral health. There were also indications of poorer clinical oral health in the ADHD group, but these results did not reach statistical significance. In conclusion, the results of this study indicate an increased prevalence of ADHD in highly dentally anxious adults and the need to pay special attention to these patients because of greater treatment needs and increased dental anxiety.
Dentists' skills with fearful patients: education and treatment
Authors: Brahm Carl‐Otto , Lundgren Jesper , Carlsson Sven G. , Nilsson Peter , Hultqvist Johanna , Hägglin Catharina 
Published: January 2013

The aims were to explore dentists' skills in dental fear, current strategies when treating fearful adult patients, and the possible need for additional education among dentists working in Sweden. A sample of 1,293 members of the Association of Public Health Dentists in Sweden were asked to respond to a Web survey concerning dental fear. The response rate was 69% (n = 889); 91% trained in Sweden and 9% trained in another country. The most frequently used pharmacological anxiety‐reducing techniques were medication with a midazolame mixture (72%) and benzodiazepine tablets (77%), and the most commonly used psychological techniques were relaxation (68%), distraction (66%), and Tell‐Show‐Do (86%). A larger proportion of dentists trained in Sweden, compared with dentists who were trained in other countries, reported that they had received undergraduate training in dental fear. Dentists trained in Sweden more often reported competence in pharmacological and psychological anxiety‐reducing techniques, compared with dentists who were trained in other countries. Higher levels of self‐rated efficacy in treating fearful patients accompanied additional education in dental fear after graduation. In conclusion, Swedish dentists use a variety of techniques to meet the needs of fearful dental patients. Competence in anxiety‐reducing techniques is associated with self‐efficacy and the site of education.
A lentiviral vector‐based genetic sensor system for comparative analysis of permeability and activity of vitamin D3 analogues in xenotransplanted human skin
Authors: Staunstrup Nicklas Heine , Bak Rasmus O. , Cai Yujia , Svensson Lars , Petersen Thomas K. , Rosada Cecilia , Stenderup Karin , Bolund Lars , Mikkelsen Jacob Giehm 
Published: January 2013

AbstractVitamin D3 analogues are widely used topical and oral remedies for various ailments such as psoriasis, osteoporosis and secondary hyperparathyroidism. In topical treatment, high skin permeability and cellular uptake are key criteria for beneficial effects due to the natural barrier properties of skin. In this study, we wish to establish an in vivo model that allows the comparison of permeability and activity of vitamin D3 analogues in human skin. We generate a bipartite, genetic sensor technology that combines efficient lentivirus‐directed gene delivery to xenotransplanted human skin with vitamin D3‐induced expression of a luciferase reporter gene and live imaging of animals by bioluminescence imaging. Based on the induction of a transcriptional activator consisting of the vitamin D receptor fused to the Gal4 DNA‐binding domain, the vitamin D3‐responsive sensor facilitates non‐invasive and rapid assessment of permeability and functional properties of vitamin D3 analogues. By topical application of a panel of vitamin D3 analogues onto ‘sensorized’ human skin, the sensor produces a drug‐induced readout with a magnitude and persistence that allow a direct comparative analysis of different analogues. This novel genetic tool has great potential as a non‐invasive in vivo screening system for further development and refinement of vitamin D3 analogues.
Aggravation of atopic dermatitis‐like symptoms by consecutive low concentration of formaldehyde exposure in NC/Nga mice
Authors: Kim Ji‐Yun , Jeong Mi Sook , Park Kui Young , Seo Seong Jun 
Published: January 2013

AbstractFormaldehyde (FA) has been known to be associated with development of asthma (AS) and atopic dermatitis (AD). In this study, we investigated whether FA inhalation would affect the provocation or exacerbation of AD‐like symptoms. Atopic‐prone NC/Nga mice were exposed to low (0.2 ppm) and high (1.0 ppm) concentration of FA by inhalation. Combined exposure to low concentration of FA inhalation and topical house dust mite (HDM) stimulation significantly upregulated HDM‐induced total plasma IgE and IgG2a production, Th1‐, Th2‐, Th17‐related cytokine as well as COX‐2 mRNA expressions in the skin. Interestingly, independent FA inhalation, especially at low concentration (0.2 ppm), increased the skin mRNA expressions of IL‐13, IL‐17E/IL‐25 and COX‐2, even though it failed to induce AD‐like skin inflammation. In conclusion, we suggest that increased skin mRNA expressions of IL‐13, IL‐25/IL‐17E and COX‐2 by independent low concentration of FA exposure might be a key factor to exacerbate HDM‐mediated AD‐like skin inflammation.
Cutaneous lymphocyte‐associated antigen as a novel predictive marker of TNF‐alpha inhibitor biological therapy in psoriasis
Authors: Jókai Hajnalka , Szakonyi József , Kontár Orsolya , Barna Gábor , Inotai Dóra , Kárpáti Sarolta , Holló Péter 
Published: January 2013

AbstractA considerable number of patients with psoriasis show secondary resistance during long‐term TNF‐alpha inhibitor therapy, necessitating the identification of reliable predictive markers. Predictive role of cutaneous lymphocyte‐associated antigen (CLA) was investigated. Thirty‐eight severe patients with psoriasis were treated for a 24‐week‐long study period. Clinical responsiveness (PASI) and changes in flow cytometry–measured peripheral lymphocyte CLA expression (week 0–2–6) were statistically analysed. Regarding 24‐week‐long treatment outcome patients were divided into two groups: During the first 6 weeks, mean CLA expression showed significant (P = 0.034604) increase among responders (32/38), while after a preliminary increase, it was significantly (P = 0.012539) decreasing in the relapsing group (6/38). Pearson's correlation analysis showed significant negative correlation between PASI and CLA changes. Responders showed (not significantly) lower initial CLA expression than relapsing patients. Our observations suggest change in CLA expression during the first 6 weeks of induction period to serve as a potential predictive marker of TNF‐alpha inhibitor therapy in psoriasis.
P2X7 receptor is required for neutrophil accumulation in a mouse model of irritant contact dermatitis
Authors: da Silva Gabriela L. , Sperotto Nathalia D. M. , Borges Thiago J. , Bonorino Cristina , Takyia Cristina M. , Coutinho‐Silva Robson , Campos Maria M. , Zanin Rafael F. , Morrone Fernanda B. 
Published: January 2013

AbstractIrritant contact dermatitis (ICD) is an inflammatory reaction caused by chemical toxicity on the skin. The P2X7 receptor (P2X7R) is a key mediator of cytokine release, which recruits immune cells to sites of inflammation. We investigated the role of P2X7R in croton oil (CrO)‐induced ICD using in vitro and in vivo approaches. ICD was induced in vivo by CrO application on the mouse ear and in vitro by incubation of murine macrophages and dendritic cells (DCs) with CrO and ATP. Infiltrating cells were identified by flow cytometry, histology and myeloperoxidase (MPO) determination. Effects of the ATP scavenger apyrase were assessed to investigate further the role of P2X7R in ICD. Animals were also treated with N‐1330, a caspase‐1 inhibitor, or with clodronate, which induces macrophage apoptosis. CrO application induced severe inflammatory Gr1+ cell infiltration and increased MPO levels in the mouse ear. Selective P2X7R antagonism with A438079 or genetic P2X7R deletion reduced the neutrophil infiltration. Clodronate administration significantly reduced Gr1+ cell infiltration and local IL‐1β levels. In vitro experiments confirmed that A438079 or apyrase treatment prevented the increase in IL‐1β that was evoked by macrophage and DC incubation with CrO and ATP. These data support a key role for P2X7 in ICD‐mediated inflammation via modulation of inflammatory cells. It is tempting to suggest that P2X7R inhibition might be an alternative ICD treatment.
AKT signalling is required for ribosomal RNA synthesis and progression of Eμ‐Myc B‐cell lymphoma in vivo
Authors: Devlin Jennifer R. , Hannan Katherine M. , Ng Pui Y. , Bywater Megan J. , Shortt Jake , Cullinane Carleen , McArthur Grant A. , Johnstone Ricky W. , Hannan Ross D. , Pearson Richard B. 
Published: January 2013

The dysregulation of PI3K/AKT/mTORC1 signalling and/or hyperactivation of MYC are observed in a high proportion of human cancers, and together they form a ‘super signalling’ network mediating malignancy. A fundamental downstream action of this signalling network is up‐regulation of ribosome biogenesis and subsequent alterations in the patterns of translation and increased protein synthesis, which are thought to be critical for AKT/MYC‐driven oncogenesis. We have demonstrated that AKT and MYC cooperate to drive ribosomal DNA (rDNA) transcription and ribosome biogenesis, with AKT being essential for rDNA transcription and in vitro survival of lymphoma cells isolated from a MYC‐driven model of B‐cell lymphoma (Eμ‐Myc) [Chan JC et al., (2011) Science Signalling 4, ra56]. Here we show that the allosteric AKT inhibitor MK‐2206 rapidly and potently antagonizes rDNA transcription in Eμ‐Myc B‐cell lymphomas in vivo, and this is associated with a rapid reduction in indicators of disease burden, including spleen weight and the abundance of tumour cells in both the circulation and lymph nodes. Extended treatment of tumour‐bearing mice with MK‐2206 resulted in a significant delay in disease progression, associated with increased B‐cell lymphoma apoptosis. Our findings suggest that malignant diseases characterized by unrestrained ribosome biogenesis may be vulnerable to therapeutic strategies that target the PI3K/AKT/mTORC1/MYC growth control network.
Use of ‘small but smart’ libraries to enhance the enantioselectivity of an esterase from Bacillus stearothermophilus towards tetrahydrofuran‐3‐yl acetate
Authors: Nobili Alberto , Gall Markus G. , Pavlidis Ioannis V. , Thompson Mark L. , Schmidt Marlen , Bornscheuer Uwe T. 
Published: January 2013

Two libraries of simultaneous double mutations in the active site region of an esterase from Bacillus stearothermophilus were constructed to improve the enantioselectivity in the hydrolysis of tetrahydrofuran‐3‐yl acetate. As screening of large mutant libraries is hampered by the necessity for GC/MS analysis, mutant libraries were designed according to a ‘small but smart’ concept. The design of focused libraries was based on data derived from a structural alignment of 3317 amino acid sequences of α/β‐hydrolase fold enzymes with the bioinformatic tool 3dm. In this way, the number of mutants to be screened was substantially reduced as compared with a standard site‐saturation mutagenesis approach. Whereas the wild‐type esterase showed only poor enantioselectivity (E = 4.3) in the hydrolysis of (S)‐tetrahydrofuran‐3‐yl acetate, the best variants obtained with this approach showed increased E‐values of up to 10.4. Furthermore, some variants with inverted enantiopreference were found.
Evidence that Na+/H+ exchanger 1 is an ATP‐binding protein
Authors: Shimada‐Shimizu Naoko , Hisamitsu Takashi , Nakamura Tomoe Y. , Wakabayashi Shigeo 
Published: January 2013

Na+/H+ exchanger (NHE) 1 is a member of the solute carrier superfamily, which regulates intracellular ionic homeostasis. NHE1 is known to require cellular ATP for its activity, despite there being no requirement for energy input from ATP hydrolysis. In this study, we investigated whether NHE1 is an ATP‐binding protein. We designed a baculovirus vector carrying both epitope‐tagged NHE1 and its cytosolic subunit CHP1, and expressed the functional NHE1–CHP1 complex on the surface of Sf9 insect cells. Using the purified complex protein consisting of NHE1 and CHP1 from Sf9 cells, we examined a photoaffinity labeling reaction with 8‐azido‐ATP‐biotin. UV irradiation promoted the incorporation of 8‐azido‐ATP into NHE1, but not into CHP1, with an apparent Kd of 29.1 µm in the presence of Mg2+. The nonlabeled nucleotides ATP, GTP, TTP and CTP all inhibited this crosslinking. However, ATP had the strongest inhibitory effect, with an apparent inhibition constant (IC50) for ATP of 2.2 mm, close to the ATP concentration giving the half‐maximal activation of NHE1 activity. Importantly, crosslinking was more strongly inhibited by ATP than by ADP, suggesting that ATP is dissociated from NHE1 upon ATP hydrolysis. Limited proteolysis with thrombin and deletion mutant analysis revealed that the 8‐azido‐ATP‐binding site is within the C‐terminal cytoplasmic domain of NHE1. Equilibrium dialysis with NHE1‐derived peptides provided evidence that ATP directly binds to the proximal cytoplasmic region (Gly542–Pro598), which is critical for ATP‐dependent regulation of NHE1. These findings suggest that NHE1 is an ATP‐binding transporter. Thus, ATP may serve as a direct activator of NHE1.