bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of HLA‐DR4‐restricted immunogenic peptide derived from xenogenic porcine major histocompatibility complex class I molecule
Authors: Park Chan‐Su , Kim Ki‐Hyang , Im Sun‐A , Song Sukgil , Lee Chong‐Kil
Published: September 2012

Park C‐S, Kim K‐H, Im S‐A, Song S, Lee C‐K. Identification of HLA‐DR4‐restricted immunogenic peptide derived from xenogenic porcine major histocompatibility complex class I molecule. Xenotransplantation 2012; 19: 317–322. © 2012 John Wiley & Sons A/S.

Abstract:  Indirect recognition of xenoantigens has been implicated as the major mechanism underlying xenospecific CD4+ T‐cell activation in chronic rejection. We identified swine leukocyte antigen (SLA)‐derived immunogenic peptides that are presented in the context of human HLA‐DR4 molecules. The SLA class I‐derived peptides that bind HLA‐DRB1*0401, a representative of the DR4 supertype, were predicted using a computer‐assisted algorithm. The candidate peptides were synthesized, and their binding capacities to HLA‐DRB1*0401 were compared in a competitive ELISA using biotinylated hemagglutinin reporter peptides [HA307‐319]. Peptide‐11 (LRSWTAADTAAQISK) was determined to exhibit the most potent binding capacity to HLA‐DRB1*0401 in vitro and thus selected for in vivo immunization. Immunization of HLA‐DRB1*0401‐transgenic mice with peptide‐11 elicited potent CD4+ Th1 responses. Peptide‐11 shares homology to α2 domains of three SLA‐1 alleles, six SLA‐2 alleles, and 14 SLA‐3 alleles. Thus, this study has important implications not only for the identification of an immunogenic indirect epitope shared by diverse SLA class I alleles, but also for the development of epitope‐specific immunoregulation strategies.
Ashwagandharoot in the treatment of non-classical adrenal hyperplasia
Authors: Kalani Amir , Bahtiyar Gul , Sacerdote Alan
Published: September 2012

Congenital adrenal hyperplasia (CAH) is a well-characterised family of disorders of the adrenal cortices, resulting in varying degrees of cortisol, aldosterone and androgen deficiency or androgen excess, depending on the enzyme(s) affected and the degree of quantitative or functional enzyme deficit.Withania somnifera(WS), commonly known asAshwagandha, is a medicinal plant that has been employed for centuries in ayurvedic medicine. Preclinical studies have shown that WS increases circulating cortisol levels and improves insulin sensitivity. We report the case of a 57-year-old woman with non-classical adrenal hyperplasia due to both 3-β-ol dehydrogenase deficiency and aldosterone synthase deficiency who was self-treated with WS for 6 months. After 6 months of treatment her serum 18-OH-hydroxycorticoserone, 17-OH-pregnenolone, corticosterone and 11-deoxycortisol decreased by 31%, 66%, 69% and 55%, respectively. The biochemical improvement was accompanied by a noticeable reduction in scalp hair loss.
PS16 Which is more Effective, A Universal or Targeted Approach, to Implementing the National Healthy Start Programme? A Mixed Methods Study
Authors: Moonan M , Hanratty B , Whitehead M
Published: September 2012

Background

Healthy Start is a statutory scheme in the UK, aiming to improve the health of children and pregnant or lactating women by providing food vouchers and vitamins. The Department of Health intended the intervention to be targeted to low incomes families (a targeted approach), but in some areas Healthy Start vitamins are available to eligible mothers and children independent of income (a universal approach). The aim of this study is to investigate which approach is more effective and to identify barriers to implementation.

Methods

1) Systematic review of the literature to identify which approach, universal vs. targeted, achieves the highest coverage of vitamin use in pre-school children and pregnant women.; 2) Using national data, a comparison of vitamin uptake rates in targeted and universal areas.; 3) In depth qualitative interviews with 30 commissioners, providers and service users from a targeted and universal area. Data were thematically analysed.

Results

1) Initial findings from the systematic literature review reveals that universal supplementation of vitamins such as folic acid significantly reduces the incidence of preventable ill health due to vitamin deficiencies such as neural tube defects compared to a targeted approach.; 2) In areas using the targeted approach, the uptake of children’s drops and women’s tablets was 1.46% and 2.56% respectively. In the area that adopted a universal approach, the uptake of children’s drops and women’s tablets was 3.97% and 7.72% respectively. ; 3) Barriers shared by both approaches include a lack of awareness of the scheme amongst health professionals, onerous administrative processes and the availability of vitamins. The universal approach is supported by health professionals because it does not stigmatise recipients.

Conclusion

1) From the systematic review, mandatory universal fortification of foods, e.g. flour is a major public health opportunity for the UK.; 2) Uptake of Healthy Start food vouchers and vitamins is low whatever the implementation strategy. However, uptake of Healthy Start vitamins is significantly higher in areas adopting a universal approach to implementation. A universal approach to implementation is supported by the literature and this study suggests that it may overcome some barriers to the implementation of the Healthy Start scheme nationally.; 3) In particular, a universal approach may reduce some of the administrative hurdles confronted by a targeted approach and will also address the stigma associated with the use of Healthy Start vitamins.

Producing evidence for the cost effectiveness of the scheme will be critical for its continued support.
THE TRANSITION FROM ERDŐS–RÉNYI PERCOLATION TO EXPLOSIVE PERCOLATION UNDER THE PARTIAL PRODUCT RULE
Authors: CHI LIPING , CAI XU
Published: September 2012

Explosive percolation proposed by Achlioptas et al. has attracted much attention recently. To understand how the product rule delays the phase transition, in this paper, we will concentrate our efforts on the influence of product rule in the transition from Erdős–Rényi (ER) percolation to Achlioptas explosive percolation. In our model, only a fraction of the adding edges will obey the product rule. With the probability p, the edge is selected under the Achlioptas's product rule; with 1 - p the edge is added between two randomly chosen nodes, that is, the ER rule. When the product rule plays a dominant role in the evolution, p > 0.5, the percolation transition delays more abruptly and instantaneously. The location of the critical points is independent of the network size and satisfies [Formula: see text], where [Formula: see text] and [Formula: see text] are the critical points of ER percolation and Achlioptas one. We present the largest gap Δs max and the critical region Δ as a function of p and N. The giant component s in terms of the edge density t above tc is also analyzed. We find that all the critical values have a linear relationship against p.
VECTOR FIELDS, VARIATIONAL EQUATIONS AND COMMUTATORS
Authors: STEEB WILLI-HANS , HARDY YORICK , TANSKI IGOR
Published: September 2012

We study autonomous systems of first order ordinary differential equations, their corresponding vector fields and the autonomous system corresponding to the vector field of the commutator of two such autonomous systems. These vector fields form a Lie algebra. From the variational equations of these autonomous systems, we form new vector fields consisting of the sum of the two vector fields. We show that these new vector fields also form a Lie algebra. Results about fixed points, first integrals and the divergence of the vector fields are also presented.
TWO KINDS OF HORSESHOES IN A HYPERCHAOTIC NEURAL NETWORK
Authors: LI QINGDU , YANG XIAO-SONG
Published: September 2012

This paper studies the hyperchaotic dynamics in a four-dimensional Hopfield neural network by virtue of topological horseshoe. Two different horseshoes (chaotic invariant sets) are found in this network with the same parameters. Numerical studies show that the first one expands only one-dimensionally and the second one expands two-dimensionally. Computer simulation also shows that there exists a heteroclinic connection from the second horseshoe to the first one, which indicates that the chaotic set of this system can have a very complicated structure composed of different kinds of expansions.
HOPF BIFURCATION OF LIÉNARD SYSTEMS BY PERTURBING A NILPOTENT CENTER
Authors: SU JING , YANG JUNMIN , HAN MAOAN
Published: September 2012

As we know, Liénard system is an important model of nonlinear oscillators, which has been widely studied. In this paper, we study the Hopf bifurcation of an analytic Liénard system by perturbing a nilpotent center. We develop an efficient method to compute the coefficients bl appearing in the expansion of the first order Melnikov function by finding a set of equivalent quantities B2l+1 which are able to calculate directly and can be used to study the number of small-amplitude limit cycles of the system. As an application, we investigate some polynomial Liénard systems, obtaining a lower bound of the maximal number of limit cycles near a nilpotent center.
GENERALIZED INDEX POLYNOMIALS FOR VIRTUAL LINKS
Authors: LEE KYEONGHUI , IM YOUNG HO
Published: September 2012

We construct some polynomial invariants for virtual links by the recursive method, which are different from the index polynomial invariant defined in [Y. H. Im, K. Lee and S. Y. Lee, Index polynomial invariant of virtual links, J. Knot Theory Ramifications19(5) (2010) 709–725]. We show that these polynomials can distinguish whether virtual knots can be invertible or not although the index polynomial cannot distinguish the invertibility of virtual knots.
THE SIMULATION OF POLYSTYRENE/NANOPARTICLES COMPOSITE MICROSPHERES USING DISSIPATIVE PARTICLE DYNAMICS
Authors: XU HAILONG , ZHANG QIUYU , ZHANG HEPENG , ZHANG BAOLIANG , YIN CHANGJIE
Published: September 2012

Dissipative particle dynamics (DPD) was initially used to simulate the polystyrene/nanoparticle composite microspheres (PNCM) in this paper. The coarse graining model of PNCM was established. And the DPD parameterization of the model was represented in detail. The DPD repulsion parameters were calculated from the cohesive energy density which could be calculated by amorphous modules in Materials Studio. The equilibrium configuration of the simulated PNCM shows that the nanoparticles were actually "modified" with oleic acid and the modified nanoparticles were embedded in the bulk of polystyrene. As sodium dodecyl sulfate (SDS) was located in the interface between water and polystyrene, the hydrophilic head of SDS stretched into water while the hydrophobic tailed into polystyrene. All simulated phenomena were consistent with the experimental results in preparation of polystyrene/nanoparticles composite microspheres. The effect of surface modification of nanoparticles on its dispersion in polystyrene matrix was also studied by adjusting the interaction parameters between the OA and NP beads. The final results indicated that the nanoparticles removed from the core of composite microsphere to the surface with increase of a OA-NP . All the simulated results demonstrated that our coarse–grained model was reasonable.
EXPLICIT FORMULAS FOR THE FOURIER COEFFICIENTS OF A CLASS OF ETA QUOTIENTS
Authors: YAO OLIVIA X. M. , XIA ERNEST X. W. , JIN J.
Published: September 2012

Recently, Williams discovered explicit formulas of the coefficients c(n) in the Fourier series expansions of a class of eta quotients. Motivated by the results obtained by Williams, we find that the coefficients c(2n) in the Fourier series expansions of another class of eta quotients can be represented as a linear combination of σ3(n), σ3(n/2), σ3(n/3) and σ3(n/6). One example is [Formula: see text] where [Formula: see text]
Fibrous Dysplasia of the Palate: Report of a Case and Review of Palatal Swellings
Authors: Shreedhar Balasundari , Kamboj Mala , Kumar Nishant , Shamim Khan Sameera
Published: September 2012

Fibrous dysplasia is a benign fibroosseous lesion characterised by the replacement of normal bone by excessive proliferation of cellular fibrous connective tissue which is slowly replaced by bone, osteoid, or cementum-like material. It causes bone pain, deformities, and pathological fractures. Fibrous dysplasia (FD) is a sporadic benign skeletal disorder that can affect one bone (monostotic form) or multiple bones (polyostotic form). In this paper, we present case of a monostotic fibrous dysplasia on the hard palate of 14-year-old girl and a tabular review of common palatal swellings.
Penile Paraffinoma
Authors: Bayraktar Necmi , Başar İsmet
Published: September 2012

Penile paraffinoma is an uncommon entity produced by penile paraffin injections for the purpose of penile enlargement by a nonmedical person. Although it is not a current method of penile enlargement procedures, in our opinion dermatologists and urology specialist should be have knowledge of this entity about diagnosis and management. It will be an aim to share our experiences and views in this paper.
Clinical Manifestations of Portal Hypertension
Authors: Al-Busafi Said A. , McNabb-Baltar Julia , Farag Amanda , Hilzenrat Nir
Published: September 2012

The portal hypertension is responsible for many of the manifestations of liver cirrhosis. Some of these complications are the direct consequences of portal hypertension, such as gastrointestinal bleeding from ruptured gastroesophageal varices and from portal hypertensive gastropathy and colopathy, ascites and hepatorenal syndrome, and hypersplenism. In other complications, portal hypertension plays a key role, although it is not the only pathophysiological factor in their development. These include spontaneous bacterial peritonitis, hepatic encephalopathy, cirrhotic cardiomyopathy, hepatopulmonary syndrome, and portopulmonary hypertension.
Chondroid Chordoma and Nasal Adenocarcinoma: An Exceptional Association
Authors: Gallet Patrice , Marcon Nathalie , Georgel Thomas , Vignaud Jean-Marie , Parietti-Winkler Cécile , Jankowski Roger
Published: September 2012

Collision tumors are exceptional, associating two independent tumoral contingents. We report a case of an association of two rare tumors: sinonasal adenocarcinoma and chondroid chordoma. Initially, only adenocarcinoma was diagnosed. The treatment consisted of endoscopic endonasal surgery followed by conventional radiotherapy. After 18 months, a local recurrence was diagnosed after a facial trauma, but the true histology was difficult to assess. The tumor was dual, associating adenocarcinoma and chondroid chordoma, with atypical localization in the ethmoid. Further evolution was particularly aggressive. We discuss the key points of this observation.
HER2 Overexpression Renders Human Breast Cancers Sensitive to PARP Inhibition Independently of Any Defect in Homologous Recombination DNA Repair
Authors: Nowsheen Somaira , Cooper Tiffiny , Bonner James A. , LoBuglio Albert F. , Yang Eddy S.
Published: September 2012

HER2 overexpression in breast cancer confers increased tumor aggressiveness. Although anti-HER2 therapies have improved patient outcome, resistance ultimately occurs. PARP inhibitors target homologous recombination (HR)-deficient tumors, such as the BRCA-associated breast and ovarian cancers. In this study, we show that HER2+ breast cancers are susceptible to PARP inhibition independent of an HR deficiency. HER2 overexpression in HER2 negative breast cancer cells was sufficient to render cells susceptible to the PARP inhibitors ABT-888 and AZD-2281 both in vitro and in vivo, which was abrogated by HER2 reduction. In addition, ABT-888 significantly inhibited NF-κB (p65/RelA) transcriptional activity in HER2+ but not HER2 negative breast cancer cells. This corresponded with a reduction in phosphorylated p65 and total IKKα levels, with a concomitant increase in IκBα. Overexpression of p65 abrogated cellular sensitivity to ABT-888, whereas IκBα overexpression reduced cell viability to a similar extent as ABT-888. Therefore, susceptibility of HER2+ breast cancer cells to PARP inhibition may be because of inhibition of NF-κB signaling driven by HER2. Our findings indicate that PARP inhibitors may be a novel therapeutic strategy for sporadic HER2+ breast cancer patients. Cancer Res; 72(18); 4796–806. ©2012 AACR.
Protective Actions of Globular and Full-Length Adiponectin on Human Endothelial Cells: Novel Insights into Adiponectin-Induced Angiogenesis
Authors: Adya Raghu , Tan Bee K. , Chen Jing , Randeva Harpal S.
Published: September 2012

Background/Aims: Adiponectin levels are decreased in diabetes and atherosclerosis. Coexisting hyperglycaemia and systemic inflammation predisposes to dysregulated angiogenesis and vascular disease. We investigated the effect of globular adiponectin (gAd) and full-length adiponectin (fAd) on angiogenesis and pro-angiogenic molecules, i.e. matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF), in human microvascular endothelial cells (HMEC-1). Methods: Angiogenesis was assessed by studying capillary tube formation in HMEC-1 on growth factor-reduced Matrigel. Endothelial cell migration assay was performed in a modified Boyden chamber. Results: Endothelial cell proliferation, in vitro migration and angiogenesis were significantly increased by gAd (mediated by AdipoR1, AMPK-Akt pathways), and gAd significantly increased MMP-2, MMP-9 and VEGF expression levels. The effect of gAd on VEGF appears to be mediated by AdipoR1, whilst the effect of gAd on MMP-2 and MMP-9 appears to be mediated by AdipoR1 and AdipoR2. Only endothelial cell proliferation was significantly increased by fAd in human microvascular endothelial cells and appears to be mediated by AdipoR2. No significant effects on MMP-2, MMP-9 and VEGF were observed. Importantly, gAd decreased glucose and C-reactive protein-induced angiogenesis with a concomitant reduction in MMP-2, MMP-9 and VEGF in HMEC-1 cells. Conclusion: We report novel insights into the mechanisms of adiponectin on angiogenesis.
New First-Trimester Crown-Rump Length Equations from a French General Population
Authors: Constant Marc , Tran Viet Chi , Benoit Bernard , Vasseur Francis
Published: September 2012

Introduction: The purpose of this study was to obtain precise knowledge of fetal biometric measurements, in particular crown-rump length (CRL). Our results have been carefully compared to equations found in the literature. Materials and Methods: Single-operator measurements of 2,123 spontaneous pregnancies from a general French population provided new statistical relationships between fetal age (FA) and CRL. Comparisons were made with measurements obtained from 402 in vitro fertilizations (IVFs) for which FA were known. Heteroskedastic and robust regressions were compared by cross-validation, and prediction errors were studied. All ultrasound measurements were taken during standard follow-ups of pregnancies, without any additional features. Results: From a cleaned subsample of 513 spontaneous pregnancies, we reported good modeling of first-term embryonic growth, with equations and predictions of standard deviations agreeing with objective datations for IVFs. Most precise CRL measurements were predicted for FA of 49 days. Discussion: Our results allow future detection of fetal growth abnormalities using Z-scores throughout the first trimester.
The Effect of Electroacupuncture on Insulin-Like Growth Factor-I and Oxidative Stress in an Animal Model of Renal Failure-Induced Hypertension
Authors: Oh Young-Il , Yang Eun Jin , Choi Sun-Mi , Kang Chang-Won
Published: September 2012

Background/Aims: The present study was performed to demonstrate the effect of electroacupuncture (EA) and acupuncture on renal failure (RF)-induced hypertension. Methods: We stimulated the Zusanli (ST36) and Taixi (KI3) acupoints in a rat model of RF-induced hypertension. Results: EA significantly reduced RF-induced hypertension (p < 0.05). In a histopathological study, increments in RF-induced glomerulosclerosis and tubulointerstitial fibrosis were attenuated by EA treatment (p < 0.05). The increase in albuminuria in the RF group was also reduced by EA treatment (p < 0.05). In blood analysis, the increment in RF-induced serum BUN and creatinine concentrations were decreased by EA (p < 0.05), and the decreases in RF-induced insulin-like growth factor-I (IGF-I) mRNA and protein levels were increased by EA in both the kidney and the serum (p < 0.05). The increases in RF-induced oxidative stress, e.g. inducible nitric oxide synthase, heme oxygenase and thiobarbituric acid-reactive substance expression, were significantly decreased in the RF-EA group (p < 0.01). Conclusion: These findings suggest that the anti-hypertensive mechanism of EA could be related to the effects of oxidative stress on IGF-I in RF-induced hypertension.
Forebrain Organization in Elasmobranchs
Authors: Hofmann Michael H. , Northcutt R. Glenn
Published: September 2012

It has long been known that many elasmobranch fishes have relatively large brains. The telencephalon, in particular, has increased in size in several groups, and as a percent of total brain weight, it is as large as in some mammals. Little is known, however, about the organization, connections, and functions of the telencephalon in elasmobranchs. Early experimental studies indicated that olfaction does not dominate the telencephalon and that other sensory modalities are represented, particularly in the pallium. We have investigated the intrinsic and extrinsic connections of the telencephalon in two elasmobranch species: the thornback guitarfish, Platyrhinoidis triseriata, and the spiny dogfish, Squalus acanthias. Tracers were injected into various parts of the forebrain and olfactory pathways were found to be extensive and were seen to involve the pallium. Injections into various parts of the pallium revealed a major input from the area basalis, which receives secondary and tertiary olfactory fibers. Nonolfactory input from the diencephalon appeared relatively minor and seemed to converge with olfactory information in the dorsal pallium and area superficialis basalis. Major descending projections were seen to originate in the dorsal pallium and terminate in the hypothalamus and – in the case of Platyrhinoidis – massively in the lateral mesencephalic nucleus. Descending pathways appeared mainly crossed in Platyrhinoidis, but not in Squalus. Our data indicate that the concept of the dorsal pallium as a nonolfactory area in elasmobranchs must be reconsidered, and we suggest that many telencephalic centers, including the dorsal pallium, are involved in olfactory orientation.
The Association between Nonalcoholic Fatty Liver Disease, Metabolic Syndrome and Arterial Stiffness in Nondiabetic, Nonhypertensive Individuals
Authors: Kim Byung Jin , Kim Nan Hee , Kim Bum Soo , Kang Jin Ho
Published: September 2012

Objectives: To assess the relationship between nonalcoholic fatty liver disease (NAFLD) and arterial stiffness in nondiabetic, nonhypertensive individuals with and without metabolic syndrome (MetS). Methods: Hepatic ultrasound and brachial-ankle pulse wave velocity (baPWV) were investigated in 4,467 individuals. The subjects were classified into normal PWV and increased PWV (≥1,366 cm/s) groups, and divided into 2 groups (non-NAFLD vs. NAFLD groups) and 3 groups (non-, mild and moderate-to-severe NAFLD groups), respectively. Results: The overall prevalence of NAFLD was 37.3% and the NAFLD group had higher levels of baPWV (control vs. NAFLD, 1,363 ± 210.3 vs. 1,388 ± 235.9 cm/s, p < 0.001). On multivariate regression analysis, NAFLD was independently associated with increased baPWV (≥1,366 cm/s), irrespective of multiple covariates (OR 1.237 and 95% CI 1.050–1.458). Subgroup analyses revealed that there was a significant association between NAFLD and baPWV only in individuals without MetS (OR 1.267 and 95% CI 1.065–1.507). The multivariate linear regression models for the overall study population and for individuals without MetS also revealed a significant association between NAFLD and the absolute value of baPWV; however, the result for individuals with MetS did not. Conclusions: Our results indicate that the presence and the degree of NAFLD are associated with arterial stiffness in nonhypertensive, nondiabetic individuals, especially in those individuals without MetS.
EML4-ALK Rearrangement and Its Clinical Significance in Chinese Patients with Advanced Non-Small Cell Lung Cancer
Authors: Wang Zhijie , Zhang Xuchao , Bai Hua , Zhao Jun , Zhuo Minglei , An Tongtong , Duan Jianchun , Yang Lu , Wu Meina , Wang Shuhang , Wang Yuyan , Wu Yilong , Wang Jie
Published: September 2012

Objective: To identify the clinicopathological characteristics and clinical outcomes of Chinese patients with non-small cell lung cancer (NSCLC) and to investigate possible associations of NSCLC with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) mutations. Methods: Patients with stage IV NSCLC were screened for EML4-ALK rearrangement and EGFR mutations at the Peking University Cancer Hospital. EML4-ALK was identified using fluorescent in situ hybridization and confirmed by immunohistochemistry. EGFR mutations were determined using denaturing high-performance liquid chromatography. Results: The incidence of EML4-ALK was 9.7% (11/113). Patients with EML4-ALK were more likely to present the EGFR wild type (WT; p = 0.033). Response to EGFR-tyrosine kinase inhibitor (TKI) was similar between patients with EML4-ALK rearrangement and EGFR mutation (33.3 vs. 46.9%, p = 0.451), but progression-free survival (PFS) was inferior compared to those with EGFR mutation (2.1 vs. 8.8 months, p = 0.032), and similar to patients with WT/nonrearrangement (2.1 vs. 2.2 months, p = 0.696; and general p = 0.023 between the three cohorts). Moreover, 2 patients with concurrent EML4-ALK and EGFR mutations had superior PFS after EGFR-TKI compared to patients with single EML4-ALK rearrangement. Conclusions: Patients with EML4-ALK conferred similar objective response rates after EGFR-TKI although inferior PFS compared to those with EGFR mutation. Coexistence of EML4-ALK and EGFR mutation might represent a separate NSCLC genotype.
Genomic Sequence and Analysis of EhV-99B1, a New Coccolithovirus from the Norwegian Fjords
Authors: Pagarete A. , Lanzén A. , Puntervoll P. , Sandaa R.A. , Larsen A. , Larsen J.B. , Allen M.J. , Bratbak G.
Published: September 2012

Coccolithoviruses are giant dsDNA viruses that infect Emiliania huxleyi, the most ubiquitous marine microalga. Here, we present the genome of the latest coccolithovirus strain to be sequenced, EhV-99B1, and compare it with two other coccolithovirus genomes (EhV-86 and EhV-163). EhV-99B1 shares a pairwise nucleotide identity of 98% with EhV-163 (the two strains were isolated from the same Norwegian fjord but in different years), and just 96.5% with EhV-86 (isolated in the same spring as EhV-99B1 but in the English Channel). We confirmed and extended the list of relevant genomic differences between these EhVs from the Norwegian fjord and EhVs from the English Channel, namely the removal/insertions of: a phosphate permease, an endonuclease, a transposase, and two specific tRNAs. As a whole, this study provided new clues and insights into the diversity and mechanisms driving the evolution of these large oceanic viruses, in particular those processes involving selfish genetic elements.
Meta-Analysis Shows Strong Positive Association of the TNF-α Gene with Tumor Stage in Bladder Cancer
Authors: Yang Zengyue , Lv Yajie , Lv Yali , Wang Yong
Published: September 2012

There is no consensus on the association between the tumor necrosis factor-α (TNF-α) gene promoter –308 A/G single nucleotide polymorphisms and bladder cancer risk. To obtain a more precise estimation of this correlation, we conducted a meta-analysis. The PubMed, MEDLINE, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases were searched for relevant published studies. Seven case-control studies with a total of 1,311 cases and 1,436 controls were identified and analyzed. A notable correlation was observed between the TNF-α genotype and bladder cancer grade (AA+GA vs. GG; odds ratio 1.96, 95% confidence interval 1.37–2.80, p = 0.0002). In summary, this meta-analysis demonstrates that the TNF-α –308 AA+GA genotype may be a marker to the tumor-invasive stage of bladder cancer.
Altered Microstructure of White Matter Except the Corpus Callosum Is Independent of Prematurity
Authors: Shim So-Yeon , Jeong Hye-Jin , Son Dong Woo , Jeong Joon Sup , Oh Se Hong , Park Sung-Yeon , Ryu Taek-Hyun , Kim Young-Bo , Cho Zang-Hee
Published: September 2012

Background: Diffusion tensor imaging (DTI) reflects the maturation of the brain microstructure. Although preterm infants are at significant risk for altered brain microstructure, it remains unclear whether this is affected by prematurity itself or other clinical factors. Objectives: To investigate DTI parameters in preterm infants at a term-equivalent age (TEA) compared with healthy term infants and to assess the associations between DTI parameters and clinical factors that may affect brain development. Methods: We studied 34 preterm infants without apparent brain lesions and 12 healthy term infants using tract-based spatial statistics. Region-of-interest analysis was performed in the posterior and anterior limbs of the internal capsule (PLIC and ALIC), corpus callosum (CC), optic radiation, and cerebral peduncle. Results: Preterm infants had significantly decreased fractional anisotropy (FA) in nearly the entire white matter (WM) compared with term infants (p < 0.01). Multiple regression analysis showed that FA in the PLIC, ALIC, optic radiation, and cerebral peduncle were positively associated with postmenstrual age (PMA) at imaging and that the apparent diffusion coefficient was negatively associated with PMA. Only FA in the CC was positively correlated with gestational age. Chronic lung disease (CLD) and postnatal infection were associated with decreased FA in the CC and PLIC, respectively. Conclusions: Preterm infants at TEA showed an altered microstructure of the WM compared with healthy term infants. The altered microstructure of the measured WM except the CC was independent of the degree of prematurity. Chronic lung disease and postnatal infection are related to localized WM alterations.
Antimicrobial Peptides and Skin: A Paradigm of Translational Medicine
Authors: Korting H.C. , Schöllmann C. , Stauss-Grabo M. , Schäfer-Korting M.
Published: September 2012

Antimicrobial peptides (AMPs) are small, cationic, amphiphilic peptides with broad-spectrum microbicidal activity against both bacteria and fungi. In mammals, AMPs form the first line of host defense against infections and generally play an important role as effector agents of the innate immune system. The AMP era was born more than 6 decades ago when the first cationic cyclic peptide antibiotics, namely polymyxins and tyrothricin, found their way into clinical use. Due to the good clinical experience in the treatment of, for example, infections of mucus membranes as well as the subsequent understanding of mode of action, AMPs are now considered for treatment of inflammatory skin diseases and for improving healing of infected wounds. Based on the preclinical findings, including pathobiochemistry and molecular medicine, targeted therapy strategies are developed and first results indicate that AMPs influence processes of diseased skin. Importantly, in contrast to other antibiotics, AMPs do not seem to propagate the development of antibiotic-resistant micro-organisms. Therefore, AMPs should be tested in clinical trials for their efficacy and tolerability in inflammatory skin diseases and chronic wounds. Apart from possible fields of application, these peptides appear suited as an example of the paradigm of translational medicine for skin diseases which is today seen as a ‘two-way road’ – from bench to bedside and backwards from bedside to bench.
Euthyroid Submedian Free T4 and Subclinical Hypothyroidism May Have a Detrimental Clinical Effect in Down Syndrome
Authors: Tenenbaum Ariel , Lebel Eyal , Malkiel Sarah , Kastiel Yael , Abulibdeh Abdulsalam , Zangen David Haim
Published: September 2012

Background: Aberrant thyroid function is highly prevalent in Down syndrome (DS). We aimed to find whether subclinical hypothyroidism (SCH) or low-normal free T4 (FT4) are associated with a detrimental clinical outcome in untreated DS patients. Methods: 157 patients assessed at Hadassah Down Syndrome Center between 2004 and 2010 by comprehensive clinical evaluation and tests for hemoglobin, FT4 and thyroid-stimulating hormone (TSH) were subdivided into subgroups including: clinical hypothyroidism, SCH, euthyroid submedian or supramedian FT4, and alternatively for euthyroidism and TSH levels (submedian or supramedian TSH). Results: Hypothyroidism was found in 21.7% and SCH in another 14.9% of the patients. Moderate/severe hypotonia were more frequent among SCH patients compared to euthyroid patients (52.6 vs. 16.4%, p = 0.002). Patient’s hemoglobin levels were lower in the euthyroid submedian FT4 group compared to the euthyroid supramedian FT4 group (10.9 vs. 0% below the normal range, p = 0.001). Interestingly, FT4 levels correlated negatively with increasing age among euthyroid DS patients (Pearson’s correlation coefficient = –0.324, p = 0.009). Conclusion: SCH and euthyroid submedian FT4 may have significant clinical sequelae, such as hypotonia and anemia. Interventional studies with l-thyroxine replacement may be indicated in these subpopulations. Our finding that FT4 levels decrease with age in DS (contrasting the general population trend) may indicate redefining the normal FT4 levels range in DS.
Methylated DNA and Total DNA in Serum Detected by One-Step Methylation-Specific PCR Is Predictive of Poor Prognosis for Breast Cancer Patients
Authors: Fujita Noriko , Nakayama Takahiro , Yamamoto Noriaki , Kim Seung Jin , Shimazu Kenzo , Shimomura Atsushi , Maruyama Naomi , Morimoto Koji , Tamaki Yasuhiro , Noguchi Shinzaburo
Published: September 2012

Purpose: We recently developed the one-step methylation-specific PCR (OS-MSP) assay which can detect methylated DNA (met-DNA) in serum with high sensitivity. To examine its prognostic value, we applied this new assay to the detection of met-DNA in serum of breast cancer patients. Methods: Serum samples taken before surgery from 336 primary invasive breast cancer patients were subjected to the OS-MSP assay for the promoter regions of GSTP1, RASSF1A, and RARβ2. The assay outcome was considered positive when methylation was detected in at least one of these three genes. Total DNA content in serum was also determined. Results: Of the 336 stage I/II patients, 33 (10%) were positive for met-DNA in serum and showed a significantly worse overall survival (OS) rate at 100 months (78 vs. 95%; p = 0.002) than those with negative findings (n = 303). Patients with high total DNA in serum (n = 112) also showed a significantly worse OS rate at 100 months (86 vs. 97%; p = 0.001) than those with low total DNA in serum (n = 224). Moreover, patients both positive for met-DNA and with high total DNA in serum (n = 18) showed a much worse OS rate at 100 months (65 vs. 94%; p < 0.001) than the others (n = 318). Conclusions: Met-DNA in serum detected with the OS-MSP assay constitutes a significant and independent prognostic factor, and its combination with total DNA in serum seems to be even more effective for prediction of prognosis for breast cancer patients.
Use of Potentially Harmful Medications and Health-Related Quality of Life among People with Dementia Living in Residential Aged Care Facilities
Authors: Bosboom Pascalle R. , Alfonso Helman , Almeida Osvaldo P. , Beer Christopher
Published: September 2012

Background: Use of potentially harmful medications (PHMs) is common in people with dementia living in Residential Aged Care Facilities (RACFs) and increases the risk of adverse health outcomes. Debate persists as to how PHM use and its association with quality of life should be measured. We designed this study to determine the association of exposure to PHM, operationalized by three different measures, with self-reported Health-Related Quality of Life among people with dementia residing in RACFs. Methods: Cross-sectional study of 351 people aged >65 years diagnosed with dementia residing in RACFs and with MMSE ≤24. The primary outcome measure was the self-rated Quality of Life – Alzheimer’s disease questionnaire (QoL-AD). We collected data on patients’ medications, age, gender, MMSE total score, Neuropsychiatric Inventory total score, and comorbidities. Using regression analyses, we calculated crude and adjusted mean differences between groups exposed and not exposed to PHM according to potentially inappropriate medications (PIMs; identified by Modified Beers criteria), Drug Burden Index (DBI) >0 and polypharmacy (i.e. ≥5 medications). Results: Of 226 participants able to rate their QoL-AD, 56.41% were exposed to at least one PIM, 82.05% to medication contributing to DBI >0, and 91.74% to polypharmacy. Exposure to PIMs was not associated with self-reported QoL-AD ratings, while exposure to DBI >0 and polypharmacy were (also after adjustment); exposure to DBI >0 tripled the odds of lower QoL-AD ratings. Conclusion: Exposure to PHM, as identified by DBI >0 and by polypharmacy (i.e. ≥5 medications), but not by PIMs (Modified Beers criteria), is inversely associated with self-reported health-related quality of life for people with dementia living in RACFs.
Persistent Agmination of Lymphomatoid Papulosis: An Ongoing Debate
Authors: Pileri A. , Bacci F. , Neri I. , Ciabatti S. , Stefoni V. , Zinzani P.L. , Patrizi A.
Published: September 2012

Background: Persistent agmination of lymphomatoid papulosis (PALP) has been a matter of controversy in the literature, some authors suggesting that it represents composite lymphoma, others localized lymphomatoid papulosis (LyP). Patient and Methods: A 64-year-old man was referred to our outpatient center complaining of papular eruptions lasting 3 years. At physical examination, he showed papulonodular lesions on the trunk and extremities. Some patches on the trunk and upper arms were also observed. Both types of lesion were biopsied and studied on histological, immunohistochemical and molecular grounds. Results: The nodular lesion revealed the classical features of LyP type A, while the patch was characterized by the presence of a superficial and deep infiltrate with perivascular and interstitial location, consisting of mature lymphocytes admixed with plasma cells and large atypical cells that became more numerous beneath the epidermis. On immunohistochemistry the two lesions presented the same profile. Conclusion: Our case suggests that PALP does not correspond to localized LyP, as it can involve different skin areas since its presentation. Furthermore it rules out the possibility that PALP is a composite lymphoma. In fact, the same cytological and phenotypic characteristics were detected in all samples, including those taken from patchy areas.
Risk Factor, Age and Sex Differences in Chronic Kidney Disease Prevalence in a Diabetic Cohort: The Pathways Study
Authors: Yu Margaret K. , Lyles Courtney Rees , Bent-Shaw Luis A. , Young Bessie A. ,   and the Pathways Authors
Published: September 2012

Background/Aims: Women with diabetes experience a disproportionately greater burden of diabetic kidney disease (DKD) risk factors compared to men; however, sex-specific differences in DKD are not well defined. The effect of age on sex differences in DKD is unknown. Methods: We performed a cross-sectional analysis of the prevalence of DKD (eGFR <60 ml/min/1.73 m2 or microalbuminuria), advanced DKD (eGFR <30 ml/min/1.73 m2), and common DKD risk factors in the Pathways Study (n = 4,839), a prospective cohort study of diabetic patients from a managed care setting. Subjects were stratified by age <60 and ≥60 years to examine for differences by age. Logistic regression models examined the association between sex and prevalence of DKD and risk factors. Results: Women of all ages had 28% decreased odds of DKD (OR 0.72, 95% CI 0.62–0.83); however, they had a greater prevalence of advanced DKD (OR 1.67, 95% CI 1.05–2.64), dyslipidemia (OR 1.42, 95% CI 1.16–1.74), and obesity (OR 1.87, 95% CI 1.60–2.20) compared to men. Women had similar odds of hypertension and poor glycemic control as men. Women ≥60 years had increased odds of advanced DKD, hypertension, dyslipidemia, and obesity compared to similarly aged men. Women <60 years had increased odds of obesity compared to their male counterparts. Conclusion: Women with diabetes had an increased prevalence of advanced DKD and common DKD risk factors compared to men and these disparities were most prominent amongst the elderly.
Comparison of Two Inflammation-Based Prognostic Scores in Patients with Unresectable Advanced Gastric Cancer
Authors: Jeong Jae-Heon , Lim Sun Min , Yun Ji Young , Rhee Gwang Won , Lim Jae Yun , Cho Jae Yong , Kim Yu Ri
Published: September 2012

Objectives: The objective of this study was to compare the usefulness of two inflammation-based prognostic scores, neutrophil to lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS), assessed at diagnosis in stage IV advanced gastric cancer (AGC). Methods: We retrospectively reviewed the medical records of 104 patients with newly diagnosed metastatic AGC treated with palliative chemotherapy. Results: In the univariate analysis, the following variables were associated with shorter overall survival (OS): poor or undifferentiated histology (p = 0.013), more than 1 metastasis (p = 0.004), the presence of lymph node metastasis (p = 0.003), the presence of bone metastasis (p = 0.019), a lower albumin level (p < 0.001), elevated C-reactive protein (p < 0.001), a high absolute neutrophil count (p = 0.016), NLR ≥3 (p < 0.001) and higher mGPS (p < 0.001 and p = 0.007, respectively). In the multivariate analysis, high NLR and mGPS were independent prognostic factors for shorter OS (p = 0.037, p < 0.001 and p = 0.010, respectively), along with lymph node metastasis (p = 0.005) and histological subtype (p = 0.048). Conclusion: This study suggests that the inflammatory markers, NLR and mGPS, are independent prognostic factors for OS in patients with unresectable AGC treated with palliative chemotherapy.
Expression Profile of Fatty Acid Metabolism Genes in Preimplantation Blastocysts of Obese and Non-Obese Mice
Authors: Königsdorf Cornelia Alice Irene , Navarrete Santos Anne , Schmidt Juliane-Susanne , Fischer Sünje , Fischer Bernd
Published: September 2012

Background: Recent studies have disclosed a close relationship between maternal obesity, fetal metabolism and pre- and postnatal development. The lipid metabolism in preimplantation embryos is a possible target of metabolic programming. Methods: 31 genes of beta-oxidation and fatty acid and cholesterol uptake, synthesis and regulation were analyzed in day 3.5 blastocysts from NZO (obese) and C57Bl/6 (normal weight) mice by RT-PCR and semiquantitative PCR. Results: The most obvious difference between both strains was the lack of the RXR gamma transcript in NZO blastocysts. In adult NZO mice, RXR gamma is detectable in most tissues. In a semiquantitative analysis, a higher transcription rate of fatty acid transport protein 4 (p = 0.004) and a reduced transcript number of fatty acid synthase (p = 0.049) was found in NZO blastocysts. Cholesterol synthesis regulation was modified in NZO blastocysts, as indicated by the ratio of sterol regulatory element-binding protein (SREBP) 2 / insulin-induced gene 1 (Insig 1) (p = 0.001). Conclusion: In mouse blastocysts enzymes and signal molecules of fatty acid and cholesterol metabolism resemble those expressed postnatally. Distinct differences in transcription rates of genes between blastocysts from obese and non-obese mothers indicate that preimplantation embryo development is an early target for metabolic programming.
Splenic Abscess after Sleeve Gastrectomy: A Report of Two Cases
Authors: Sakran Nasser , Ilivitzki Anat , Zeina Abdel-Rauf , Assalia Ahmad
Published: September 2012

Objective: Partial demarcation and infarction of the upper pole of the spleen is not a rare occurrence after laparoscopic sleeve gastrectomy (LSG). However, development of an abscess in the absence of leakage is extremely rare. Case Reports: We present herein two unusual case reports of splenic abscess in patients following LSG.
Alu-Alu Fusion Sequences Identified at Junction Sites of Copy Number Amplified Regions in Cancer Cell Lines
Authors: Kitada K. , Aikawa S. , Aida S.
Published: September 2012

Alu elements are short, ∼300-bp stretches of DNA and are the most abundant repetitive elements in the human genome. A large number of chromosomal rearrangements mediated by Alu-Alu recombination have been reported in germline cells, but only a few in somatic cells. Cancer development is frequently accompanied by various chromosomal rearrangements including gene amplification. To explore an involvement of Alu-Alu fusion in gene amplification events, we determined 20 junction site sequences of 5 highly amplified regions in 4 cancer cell lines. The amplified regions exhibited a common copy number profile: a stair-like increase with multiple segments, which is implicated in the breakage-fusion-bridge (BFB) cycle-mediated amplification. All of the sequences determined were characterized as head-to-head or tail-to-tail fusion of sequences separated by 1–5 kb in the genome sequence. Of these, 4 junction site sequences were identified as Alu-Alu fusions between inverted, paired Alu elements with relatively long overlapping sequences of 17, 21, 22, and 24 bp. Together with genome mapping data of Alu elements, these findings suggest that when breakages occur at or near inverted, paired Alu elements in the process of BFB cycle-mediated amplification, sequence homology of Alu elements is frequently used to repair the broken ends.
Interaction between the MJO and Polar Circulations
Authors: Flatau Maria , Kim Young-Joon
Published: September 2012

A tropical–polar connection and its seasonal dependence are examined using the real-time multivariate Madden–Julian oscillation (MJO) (RMM) index and daily indices for the annular modes, the Arctic Oscillation (AO) and the Antarctic Oscillation (AAO). On the intraseasonal time scale, the MJO appears to force the annular modes in both hemispheres. On this scale, during the cold season, the convection in the Indian Ocean precedes the increase of the AO/AAO. Interestingly, during the boreal winter (Southern Hemisphere warm season), strong MJOs in the Indian Ocean are related to a decrease of the AAO index, and AO/AAO tendencies are out of phase. On the longer time scales, a persistent AO/AAO anomaly appears to influence the convection in the tropical belt and impact the distribution of MJO-preferred phases. It is shown that this may be a result of the sea surface temperature (SST) changes related to a persistent AO, with cooling over the Indian Ocean and warming over Indonesia. In the Southern Hemisphere, the SST anomalies are to some extent also related to a persistent AAO pattern, but this relationship is much weaker and appears only during the Southern Hemisphere cold season. On the basis of these results, a mechanism involving the air–sea interaction in the tropics is suggested as a possible link between persistent AO and convective activity in the Indian Ocean and western Pacific.