bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Manifestations and Treatment Options in Patients with Cirrhosis and Diabetes Mellitus
Authors: Gundling F. , Seidl H. , Strassen I. , Haller B. , Siegmund T. , Umgelter A. , Pehl C. , Schepp W. , Schumm-Draeger P.M.
Published: January 2013

Background: Diabetes is frequently diagnosed in patients with cirrhosis and represents an important risk factor for morbidity and mortality. Pharmacological therapy is limited due to hepatotoxicity and the risk of hypoglycemia. Investigations on medical practice in this patient population, frequency of diabetes-associated complications and the impact of quality of metabolic control are rare. Aims and Methods: A retrospective analysis was performed to compare the effects of hypoglycemic treatment, the achieved glycemic control under therapy, the prevalence of typical cirrhosis-related or microangiopathic complications, and cardiovascular comorbidities between a group of diabetic patients with cirrhosis (n = 87) and a nondiabetic cirrhotic population (n = 198). Results: The prevalence of diabetes in our cohort was 30.5%. Of all diabetic patients, 39.1% received therapy which might potentially result in serious side effects in patients with end-stage liver disease. The rate of ongoing alcohol abuse (28.7%) and noncompliance under medication (41.4%) was high. Only 28.7% of all diabetic subjects showed satisfactory (as defined by HbA1c ≤ 6.5%) glycemic control under therapy. Patients achieving satisfactory control experienced a lower rate of certain cirrhosis-related complications such as hepatic encephalopathy (HE) and hepatocellular carcinoma (HCC), arterial hypertension, and hypercholesterolemia. HE was significantly more frequent in diabetic than nondiabetic cirrhotic patients [HE 36.6% (diabetics) vs. 20.7% (non-diabetics), p = 0.001; ORadj = 3.21 (CI: 1.63, 6.28)], whereas no significant difference in the frequency of HCC [18.4% (diabetics) vs. 14.1% (nondiabetics), p = 0.606] was observed. In the majority of our diabetic population (59.7%), no microvascular damage was diagnosed. However, diabetic patients had a borderline significant high prevalence of arterial hypertension [48.3% (diabetics) vs. 26.8% (nondiabetics), p = 0.078; ORadj = 1.68 (CI: 0.944, 2.978)] and high cholesterol levels [17.2% (diabetics) vs. 8.6% (nondiabetics), p = 0.120, ORadj = 1.93 (CI: 0.842, 4.410)]. Conclusion: Antidiabetic therapy in cirrhotic diabetic patients often seems to be inappropriate in everyday medicine, while glycemic control is frequently not satisfactory, possibly due to incompliance or insufficient metabolic control. HE occurs more often in cirrhotic patients with diabetes than in nondiabetic patients with cirrhosis. The rate of macro- and microangiopathic complications even in the diabetic cohort is low.
Alteration of Histone H3 Lysine 4 Trimethylation on Putative Lytic Gene Promoters by Human Set1 Complex during Reactivation of Kaposi’s Sarcoma-Associated Herpesvirus
Authors: Jong Jae Eun , Cha Seho , Jang Jun Hyeong , Seo Taegun
Published: January 2013

Objective: Histone H3 lysine 4 is trimethylated by the human Set1 complex, which regulates the activation of gene expression. The aim of this study was to identify whether the levels of histone H3 lysine 4 trimethylation (H3K4me3) and the recruitment of human Set1 complex at the promoter regions of lytic genes quantitatively change during reactivation from latent to lytic infection of Kaposi’s sarcoma-association herpesvirus (KSHV). Methods: During KSHV reactivation, global changes of H3K4 methylation in KSHV-infected cells were analyzed by Western blot. The relative levels of association between proteins and promoter regions were determined by chromatin immunoprecipitation assay and quantitative real-time PCR using specific antibodies and primer sets. Results: Our results showed that KSHV reactivation does not alter the overall cellular levels of H3K4 methylation. We observed that the switch from latency to lytic cycle leads to upregulation of H3K4me3 at the active lytic genes. We also found that the recruitment of RNA pol II and subunits of human Set1 complex were enriched at the same regions in response to KSHV reactivation. Conclusion: These results demonstrate that the increase of H3K4me3 by human Set1 complex is involved in activation of lytic genes during the lytic infection of KSHV.
Investigating the Effect of CoCl2 Administration on Diabetic Nephropathy and Associated Aortic Dysfunction
Authors: Deshmukh A.B. , Patel J.K. , Prajapati A.R. , Mishra Bharat
Published: January 2013

Aim: Endothelial dysfunction appears to be a consistent finding in diabetic nephropathy. The study aimed to investigate the effect of cobalt chloride in the amelioration of endothelial dysfunction in uninephrectomized diabetic rats. Methods: We examined the effect of CoCl2 (10 mg/kg, i.p., OD = once a day) treatment on contractile responses to angiotensin II (10–10 to 10–6M) in an aortic preparation of control rats and uninephrectomized diabetic control rats. Blood glucose, plasma urea, creatinine, uric acid, aortic endothelial nitric oxide synthase (eNOS), nitrate/nitrite (NOx), superoxide dismutase, catalase and reduced glutathione levels were checked in the different groups. Results: A significant attenuation of the augmented responses to angiotensin II was observed in CoCl2-treated animals along with a fall in plasma urea, creatinine and uric acid levels. A significant reduction in blood glucose and an increase in aortic eNOS and NOx levels along with antioxidants levels were observed. Conclusion: Chronic hypoxia augments angiotensin II responses in the thoracic aorta of uninephrectomized diabetic control rats. CoCl2 attenuates these enhanced vascular responses with a significant decrease in blood glucose signifying stabilization of the hypoxia-inducible factor in the alleviation of endothelial dysfunction in diabetic nephropathy.
Y402H Polymorphism in Complement Factor H and Age-Related Macular Degeneration in the Tunisian Population
Authors: Habibi I. , Sfar I. , Kort F. , Aounallah-Skhiri H. , Chebil A. , Chouchene I. , Bouraoui R. , Limaiem R. , Largheche L. , Jendoubi-Ayed S. , Makhlouf M. , Ben Abdallah T. , Ayed K. , El Matri L. , Gorgi Y.
Published: January 2013

To evaluate a possible association between the complement factor H (CFH) Y402H polymorphism and susceptibility to age-related macular degeneration (AMD) in the Tunisian population, as well as the impact of the genotype distribution among different phenotypes and the response to treatment with intravitreal bevacizumab, exon 9 of CFH was analyzed for the Y402H polymorphism by direct sequencing in 135 healthy controls and 127 sporadic unrelated AMD patients classified into the following groups: 12 atrophic AMD (group G1), 115 exudative AMD (G2) and 10 AMD patients who had fibrovascular scarring (G3) that did not allow a precise grading of the phenotype. Seventy patients in G2 were treated with 1.25 mg intravitreal bevacizumab at 6-week intervals until choroidal neovascularization (CNV) was no longer active. The frequency of the CFH 402H allele was significantly higher in AMD patients than in controls (p = 2.62 × 10–16). However, subgroup analysis does not reveal any association between the variant allele H and phenotypes of AMD or CNV. Also, there was no significant difference in response to bevacizumab treatment according to Y402H CFH genotype (p = 0.59). A strong association of the 402H allele with susceptibility to AMD in the Tunisian population was confirmed; however, this variant does not appear to be involved in the clinical progression of this disease or in the postintravitreal bevacizumab response.
Relation of Epicardial Fat Thickness and Cardio-Ankle Vascular Index to Complexity of Coronary Artery Disease in Nondiabetic Patients
Authors: Gökdeniz Tayyar , Turan Turhan , Aykan Ahmet Çağrı , Gül İlker , Boyacı Faruk , Hatem Engin , Bektaş Hüseyin , Çelik Şükrü
Published: January 2013

Objectives: Arterial stiffness and epicardial fat thickness (EFT) are associated with coronary artery disease (CAD). The cardio-ankle vascular index (CAVI) is a novel marker of arterial stiffness. The SYNTAX score (SS) reflects the complexity of CAD. We aimed to evaluate the relation of EFT and CAVI with CAD complexity in nondiabetic patients. Method: We enrolled 121 patients undergoing coronary angiography. In all patients, CAVI and EFT were determined. SS were calculated. The relationship between EFT, CAVI and SS was analyzed. Results: CAVI and EFT were significantly correlated with SS (r = 0.537, p < 0.001, and r = 0.629, p < 0.001, respectively) and found to be independent predictors of intermediate-high SS. For the prediction of intermediate-high SS, receiver-operating characteristic curve analysis revealed a cutoff value of 5 mm for EFT (area under the curve, AUC = 0.851, 95% confidence interval, CI, 0.775–0.910) with a specificity of 92.2% and a sensitivity of 77.4% and 8.6 for CAVI (AUC = 0.877, 95% CI 0.805–0.929) with a specificity of 68.9% and a sensitivity of 93.5%. Conclusion: CAD complexity is associated with adverse cardiovascular events. It can be predicted noninvasively with EFT and CAVI in nondiabetic patients with suspected CAD. Thus, patients at high risk for cardiovascular events may be detected early and managed with appropriate treatment strategies.
(Re)Framing Educational Possibility: Attending to Power and Equity in Shaping Access to and within Learning Opportunities
Authors: Hand Victoria , Penuel William R. , Gutiérrez Kris D.
Published: January 2013

Accounts of how culture constitutes the learning activities we accomplish with others are flourishing. These accounts illustrate how participants draw upon, adapt, and contest historically situated social practices, tools, and relations to accomplish their learning goals [Vygotsky: Cambridge, Harvard University Press, 1978]. Yet, they often lack attention to the ways that these social features reify and are reified by broader power structures and hierarchies. One way that power plays out in everyday social interaction is through the stories, narratives and ideologies that serve as resources for interpreting and organizing ongoing activity. Individuals become attuned to, coordinate and mobilize around these broader narratives through the frames they engage in moments of interaction. We offer frame analysis as a means of investigating both access to learning environments and opportunities to learn within them. To situate learning opportunities within and across different components of multilevel systems, a distinction is proposed between framing within a classroom or learning environment and framing access to educational processes and institutions. This paper recommends that researchers analyze, and design for, framing that disrupts predominant power structures and expands the possibilities for learning within more equitable social practices.
Racial Storylines and Implications for Learning
Authors: Nasir Na’ilah Suad , Snyder Cyndy R. , Shah Niral , Ross Kihana Miraya
Published: January 2013

In this article, we theorize the relation between race and schooling and consider the implications for learning. While the body of research on culture and learning has come to define learning as an inherently cultural and social process, scholars have few theoretical tools to help us think about the role of race and racism in relation to students’ access to identities as learners and to learning. We draw on both theoretical and empirical literature to make three core arguments: (a) racial ‘storylines’ or narratives are prevalent in our society and have powerful implications for learners, particularly for youth from marginalized communities; (b) these racial storylines are a critical aspect of life in schools, which serve the purpose of racially and academically socializing students; and (c) as these storylines are invoked in school settings, certain identities are made available, imposed, or closed down. Such identities have important implications for students’ opportunities to learn and their engagement in learning settings. As we conclude, we consider the potential of alternative spaces, which can serve to counter dominant narratives about who is capable of learning and how learning takes place, and open new spaces for identity and learning.
Safe Use of Citric Acid-Based Dialysate and Heparin Removal in Postdilution Online Hemodiafiltration
Authors: Aniort Julien , Petitclerc Thierry , Créput Caroline
Published: January 2013

Background: Anticoagulation of the blood circuit with heparin is essential for hemodialysis, but exposes patients to several risks (bleeding, thrombocytopenia, etc.). The use of citric acid-based dialysate (CitA-D) allows the reduction of heparin in conventional hemodialysis. We evaluated the feasibility of using CitA-D in postdilution online hemodiafiltration (OL-HDF) and of removing heparin. Methods: We prospectively compared chlorhydric acid-based dialysate with CitA-D in 10 patients treated by OL-HDF. First, we reduced heparin by half the dose and then we totally removed anticoagulation. Results: For all 120 sessions using heparin-free CitA-D, only one clotting episode related to an arteriovenous fistula stenosis was observed. No adverse clinical effect was observed. (Kt/V)sp, predialytic serum bicarbonate, calcium, phosphate, parathroid hormone, and β2-microglobulin remained the same in all cases. Conclusion: Our data suggest that the use of CitA-D in OL-HDF is safe and allows heparin removal in most patients.
Review Article on Current Applications and Future Concepts of Capsule Endoscopy
Authors: Neumann Helmut , Fry Lucía C. , Neurath Markus F.
Published: January 2013

Since the advent of capsule endoscopy (CE) more than one decade has passed. During this time, extensive efforts have been made to proof the relevance of CE for diagnosis of various disease entities within the esophagus, small bowel, and colon. To date, the most common indications for CE are obscure gastrointestinal bleeding, Crohn’s disease, polyposis syndromes and evaluation of patients with complicated celiac disease. In this review we will focus on the current clinical applications of CE for imaging of the esophagus, small bowel and colon and will additionally give an outlook on future concepts and developments of CE.
Serum Ferritin Is an Independent Prognostic Factor in Chinese with Myelodysplastic Syndromes Classified as IPSS Intermediate-1
Authors: Li Bing , Xu Zefeng , Gale Robert Peter , Qin Tiejun , Zhang Yue , Xiao Zhijian
Published: January 2013

Background: The International Prognostic Staging System (IPSS) for myelodysplastic syndromes (MDS) was developed predominately in patients of European ancestry and is not validated in Asians. In a recently revised IPSS (IPSS-R), several new prognostic variables are included, i.e. age, Eastern Cooperative Oncology Group performance score (ECOG PS), serum ferritin and lactate dehydrogenase. Chinese with MDS offer a unique opportunity to distinguish the prognostic impacts of haemoglobin (HGB) concentration, red blood cell (RBC) transfusions and serum ferritin because in China, patients rarely receive RBC transfusions unless the HGB concentration is <6.0 g/dl. Methods: We studied prognostic variables in 191 untreated Chinese primary patients with MDS intermediate-1 (INT-1) in the IPSS. Results: Serum ferritin level ≥500 µg/l at diagnosis was a strong independent predictor of survival. Although baseline serum ferritin level was inversely correlated with baseline HGB, it was the serum ferritin, not the baseline HGB level, that was significantly correlated with survival in Chinese patients. A new prognostic scoring system including the ECOG PS, absolute neutrophil level, serum ferritin, percentage of bone marrow blasts and poor karyotype was developed for Chinese with IPSS INT-1 MDS. Conclusions: This revised scoring system identified a subgroup of Chinese with MDS and INT-1 IPPS who have a poor prognosis and may benefit from more intensive therapy.
An Efficient Method for Isolation of Hantaan Virus through Serial Passages in Suckling Mice
Authors: Li J.-L. , Ling J.-X. , Chen L.-J. , Wei F. , Luo F. , Liu Y.-Y. , Xiong H.-R. , How W. , Yang Z.-Q.
Published: January 2013

Objective: Hantaan virus (HTNV) is one of the main etiologic agents for hemorrhagic fever with renal syndrome in China. However, it is very difficult to isolate the virus from its original host, which hampers the viral characterization. This study describes an efficient method for isolating HTNV in suckling mice. Methods: Hantavirus-infected Apodemus agrarius were screened by quantitative real-time PCR. The homogenates of one positive rodent lung tissue were inoculated into suckling mice for virus propagation through serial passages. Results: During the three passages in suckling mice, the number of viral RNA copies/nanogram of GAPDH mRNA increased significantly ranging from 477 to 7,278 and 46 to 4,898 in the tissues of brain and lung, respectively. Hantaviral antigens could be detected by indirect immunofluorescence assay and around 100-nm virion-like structures were also observed in brain tissue by transmission electron microscopy. No nucleotide exchange was found except for one in the 3′-non-coding domain of S segment when comparing the complete genome sequences from hantavirus in the first and the third passages. Conclusion: These results suggest inoculation of suckling mice with suspected hantavirus-infected rodent samples is an efficient method for isolation and maintenance of HTNV.
Patterns of Brain Atrophy in Clinical Variants of Frontotemporal Lobar Degeneration
Authors: Lu Po H. , Mendez Mario F. , Lee Grace J. , Leow Alex D. , Lee Hyun-Woo , Shapira Jill , Jimenez Elvira , Boeve Bradley B. , Caselli Richard J. , Graff-Radford Neill R. , Jack Clifford R. , Kramer Joel H. , Miller Bruce L. , Bartzokis George , Thompson Paul M. , Knopman David S.
Published: January 2013

Background/Aims: The clinical syndromes of frontotemporal lobar degeneration include behavioral variant frontotemporal dementia (bvFTD) and semantic (SV-PPA) and nonfluent variants (NF-PPA) of primary progressive aphasia. Using magnetic resonance imaging (MRI), tensor-based morphometry (TBM) was used to determine distinct patterns of atrophy between these three clinical groups. Methods: Twenty-seven participants diagnosed with bvFTD, 16 with SV-PPA, and 19 with NF-PPA received baseline and follow-up MRI scans approximately 1 year apart. TBM was used to create three-dimensional Jacobian maps of local brain atrophy rates for individual subjects. Results: Regional analyses were performed on the three-dimensional maps and direct comparisons between groups (corrected for multiple comparisons using permutation tests) revealed significantly greater frontal lobe and frontal white matter atrophy in the bvFTD relative to the SV-PPA group (p < 0.005). The SV-PPA subjects exhibited significantly greater atrophy than the bvFTD in the fusiform gyrus (p = 0.007). The NF-PPA group showed significantly more atrophy in the parietal lobes relative to both bvFTD and SV-PPA groups (p < 0.05). Percent volume change in ventromedial prefrontal cortex was significantly associated with baseline behavioral symptomatology. Conclusion: The bvFTD, SV-PPA, and NF-PPA groups displayed distinct patterns of progressive atrophy over a 1-year period that correspond well to the behavioral disturbances characteristic of the clinical syndromes. More specifically, the bvFTD group showed significant white matter contraction and presence of behavioral symptoms at baseline predicted significant volume loss of the ventromedial prefrontal cortex.
Prediction of Sustained Virologic Response Based on Week 4 and Week 12 Response in Hepatitis C Virus Genotype 1 Patients Treated with Peginterferon and Ribavirin: Assessment in a Favorable IL28B Allele-Prevalent Area
Authors: Chung Hyun Jung , Lee Jin-Woo , Kim Young Soo , Lee Jung Il
Published: January 2013

Objectives: The aim of this study was to evaluate rapid virologic response (RVR) rate after peginterferon (PegIFN) and ribavirin (RBV) dual combination therapy in Korean hepatitis C virus (HCV) genotype 1 patients whose IL28B polymorphism is generally favorable. This study also assessed the value of RVR in predicting sustained virologic response (SVR). Methods: Treatment-naïve HCV genotype 1 patients who underwent initial treatment with either PegIFN-α-2a or α-2b and RBV were retrospectively evaluated. From 148 patients, 115 met inclusion criteria for the final analysis. Results: Overall RVR rate was 47.8% and SVR rate was 67.8% (78/115). Positive RVR had the highest positive predictive value (PPV) for achieving SVR, whereas it had the lowest negative predictive value (NPV). Undetectable HCV RNA at treatment week 12, namely complete early virologic response (cEVR), had high PPV as well as high NPV. Factors predisposing SVR were absence of liver cirrhosis and achievement of RVR or cEVR. Conclusion: This study showed RVR rate close to 50% in HCV genotype 1 patients treated with dual combination therapy in the region where favorable IL28B polymorphism is reported to be as high as 90%. Even for the patients who failed to achieve RVR, positive cEVR demonstrated a fair chance of achieving SVR.
The Effect of Testosterone on the Formation of Brain Structures
Authors: Filová Barbora , Ostatníková Daniela , Celec Peter , Hodosy Július
Published: January 2013

It has been confirmed in several studies that testosterone can significantly affect brain development. Following metabolism of this hormone by 5α-reductase to dihydrotestosterone, testosterone may act via androgen receptors, or after conversion by aromatase to estradiol, it may act via estrogen receptors. The parts of the brain which are changed under the influence of sex hormones are known as sexually dimorphic nuclei, especially in the preoptic area of the hypothalamus. Nevertheless, evidence suggests that testosterone also influences the structure of the hippocampus, specifically CA1 and CA3 areas of the hippocampus, as well as the amygdala. These brain areas are designed to convert information from short-term into long-term memory. In this review, we summarize the effects of testosterone on the organization of brain structures with respect to spatial cognitive abilities in small rodents.
Gender Differences in the Long-Chain Polyunsaturated Fatty Acid Status: Systematic Review of 51 Publications
Authors: Lohner Szimonetta , Fekete Katalin , Marosvölgyi Tamás , Decsi Tamás
Published: January 2013

Background/Aims: Sex hormones may influence the activity of enzymes which are involved in the synthesis of long-chain polyunsaturated fatty acids. The objective of this review was to assess the role of gender in determining the fatty acid composition of human samples, like plasma and erythrocyte membrane lipids, and adipose tissue. Methods: The method included a structured search strategy on MEDLINE, Scopus and the Cochrane databases, with formal inclusion/exclusion criteria, data extraction procedure and meta-analysis. Results: We evaluated 51 publications, dated from 1975 to 2011. Meta-analysis showed significantly lower values of both arachidonic acid (AA) and docosahexaenoic acid (DHA) in total plasma lipids (32 and 33 studies) and in plasma phospholipids (PL; 21 and 23 studies) in men than in women. Primary analysis of the phospholipid fraction showed the mean difference in AA to be 0.42% weight/weight (95% CI: 0.18–0.65, n = 7,769) and in DHA 0.37% weight/weight (95% CI: 0.24–0.51, n = 8,541), while there was no gender difference in the values of linoleic acid and α-linolenic acid. Conclusions: This systematic review based on 51 publications showed significantly lower contribution of AA and DHA to plasma total lipids and plasma PL in men than in women. Gender distribution should be regarded as a significant potential confounding factor in every study assessing data on fatty acid composition.
Accelerated Healing of Full-Thickness Wounds by Genipin-Crosslinked Silk Sericin/PVA Scaffolds
Authors: Aramwit Pornanong , Siritienthong Tippawan , Srichana Teerapol , Ratanavaraporn Juthamas
Published: January 2013

Silk sericin has recently been studied for its advantageous biological properties, including its ability to promote wound healing. This study developed a delivery system to accelerate the healing of full-thickness wounds. Three-dimensional scaffolds were fabricated from poly(vinyl alcohol) (PVA), glycerin (as a plasticizer) and genipin (as a crosslinking agent), with or without sericin. The physical and biological properties of the genipin-crosslinked sericin/PVA scaffolds were investigated and compared with those of scaffolds without sericin. The genipin-crosslinked sericin/PVA scaffolds exhibited a higher compressive modulus and greater swelling in water than the scaffolds without sericin. Sericin also exhibited controlled release from the scaffolds. The genipin-crosslinked sericin/PVA scaffolds promoted the attachment and proliferation of L929 mouse fibroblasts. After application to full-thickness rat wounds, the wounds treated with genipin-crosslinked sericin/PVA scaffolds showed a significantly greater reduction in wound size, collagen formation and epithelialization compared with the control scaffolds without sericin but lower numbers of macrophages and multinucleated giant cells. These results indicate that the delivery of sericin from the novel genipin-crosslinked scaffolds efficiently healed the wound. Therefore, these genipin-crosslinked sericin/PVA scaffolds represent a promising candidate for the accelerated healing of full-thickness wounds.
Evaluation of the Therapeutic Benefit of Delayed Administration of Erythropoietin following Early Hypoxic-Ischemic Injury in Rodents
Authors: Alexander M.L. , Hill C.A. , Rosenkrantz T.S. , Fitch R.H.
Published: January 2013

Hypoxia-ischemia (HI) and associated brain injuries are seen in premature as well as term infants with birth complications. The resulting impairments involve deficits in many cognitive domains, including language development. Poor rapid auditory processing is hypothesized to be one possible underlying factor leading to subsequent language delays. Mild hypothermia treatment for HI injuries in term infants is widely used as an intervention but can be costly and time consuming. Data suggest that the effectiveness of hypothermia treatment following HI injury declines beyond 6 h following injury. Consequently, the availability of a therapeutic alternative without these limitations could allow doctors to treat HI-injured infants more effectively and thus reduce deleterious cognitive and language outcomes. Evidence from both human studies and animal models of neonatal HI suggests that erythropoietin (Epo), an endogenous cytokine hormone, may be a therapeutic agent that can ameliorate HI brain injury and preserve subsequent cognitive development and function. The current study sought to investigate the therapeutic effectiveness of Epo when administered immediately after HI injury, or delayed at intervals following the injury, in neonatal rodents. Rat pups received an induced HI injury on postnatal day 7, followed by an intraperitoneal injection of Epo (1,000 U/kg) immediately, 60 min, or 180 min following induction of injury. Subjects were tested on rapid auditory processing tasks in juvenile (P38-42) and adult periods (P80-85). Ventricular and cortical size was also measured from post mortem tissue. Results from the current study show a therapeutic benefit of Epo when given immediately following induction of HI injury, with diminished benefit from a 60-min-delayed injection of Epo and no protection following a 180-min-delayed injection. The current data thus show that the effectiveness of a single dose of Epo in ameliorating auditory processing deficits following HI injury decreases precipitously as treatment is delayed following injury. These data may have important implications for experimental human neonatal intervention with Epo.
Influences of Personality Traits on Quality of Life after Stroke
Authors: Kim Seon-Young , Kim Jae-Min , Stewart Robert , Kang Hee-Ju , Kim Sung-Wan , Shin Il-Seon , Park Man-Seok , Cho Ki-Hyun , Yoon Jin-Sang
Published: January 2013

Objective: To investigate influences of personality traits on quality of life (QOL) over the first 3 months after stroke. Methods: Participants were interviewed 2 weeks after stroke with a follow-up after 3 months, with QOL (WHOQOL-BREF) measured on both occasions. Personality traits were ascertained at the 3-month examination using the Big Five Inventory, quantifying five personality traits: extraversion, agreeableness, conscientiousness, neuroticism and openness. Influences of personality traits on QOL at the 2 examinations were investigated using repeated-measure analysis of variance (ANOVA) with adjustments for age, gender, number of years in education, use of antidepressants, stroke severity and physical disability. Results: In the 151 patients present at both examinations, neuroticism resulted in lower overall QOL levels on all 4 WHOQOL-BREF domains, and extraversion, agreeableness and conscientiousness influenced some, but not all, QOL domains. The openness trait had no influence on overall QOL levels but showed significant group-by-time interactions on psychological and environment QOL domains. Conclusions: QOL over the 3-month period after stroke was influenced by several personality traits. The neuroticism trait influenced overall QOL levels but not trajectories, while the opposite was true for the openness trait.
Serum Acute Phase Protein and Inflammatory Cytokine Network Correlations: Comparison of a Pre-Rheumatoid Arthritis and Non-Rheumatoid Arthritis Community Cohort
Authors: Masi Alfonse T. , Rehman Azeem A. , Elmore Kevin B. , Aldag Jean C.
Published: January 2013

Serum concentrations of acute phase proteins, inflammatory cytokines, and other immunological components were individually assayed using high-sensitivity ELISA in a com-munity-based cohort of preclinical rheumatoid arthritis (pre-RA) and matched non-RA control (CN) subjects. Bivariate correlations of the biomarker panel concentrations were compared in pre-RA versus CN and female versus male subjects. Clinically elevated CRP levels (8+ mg/l) occurred in a higher (p = 0.010) frequency in 46 pre-RA (n = 8, 17.4%) subjects than in 179 CN (n = 9, 5.0%), and were independent of age, gender, smoking behaviors, and serum rheumatoid factor. Selected age and gender differences were found in levels of the immunological network factors. In each study group, the ratio of sTNF-RI to IL-2sRα mean concentrations was 2-fold higher in men than in women. Aging correlated positively with CRP, ASAA, and TNF-α levels, but negatively with IL-1β. Bivariate correlations were similar in pre-RA subjects versus CN and by gender, with few exceptions. Factor loadings in principal component analysis of the total subjects indicated that age- and gender-related variables constituted the two main components. Using multiple regression analyses, an integrative working model of all variable interrelations was generated. The tentative, directional model supports a concept of gender dimorphism of the ratio of sTNF-RI to IL-2sRα serum concentrations and displays differing effects of age on TNF-α versus IL-1β levels. These findings indicate complex age, gender, and cytokine interrelations in control of the immune systems network. Future research in testing such inflammatory pathways promises a better understanding of predisposition to diseases, like RA.
Acute Leukemia Showing t(8;22)(p11;q11), Myelodysplasia, CD13/CD33/CD19 Expression and Immunoglobulin Heavy Chain Gene Rearrangement
Authors: Shimanuki Masaya , Sonoki Takashi , Hosoi Hiroki , Watanuki Jyuri , Murata Shogo , Mushino Toshiki , Kuriyama Kodai , Tamura Shinobu , Hatanaka Kazuo , Hanaoka Nobuyoshi , Nakakuma Hideki
Published: January 2013

t(8;22)(p11;q11) is a rare but recurrent chromosome translocation that has been reported in 11 cases of myeloproliferative neoplasm or B-acute lymphoblastic leukemia. This translocation results in an in-frame fusion of FGFR1 on 8p11 and BCR on 22q11, and causes constitutive activation of the tyrosine kinase of the BCR/FGFR1 chimera protein. Here, we report the twelfth case of hematological tumor bearing t(8;22)(p11;q11). The bone marrow showed hypoplastic and tri-lineage dysplasia with 24.4% abnormal cells. The abnormal cells were not defined as myeloid or lymphoid morphologically, lacking a myeloperoxidase reaction. Flow cytometric analysis of the bone marrow cells revealed that the abnormal cells expressed CD13, CD33, CD34, and CD19, and that a fraction of the abnormal cells was positive for CD10. Southern blot analysis of the bone marrow cells showed rearrangement of the immunoglobulin heavy chain gene, a genetic hallmark of B-cell differentiation. Previously reported cases with t(8;22)(p11;q11) suggested an association between myeloid and B-lymphoid tumors, whereas other chromosome translocations involving FGFR1 on 8p11 showed a link between myeloid and T-lymphoid tumors. Our observation supports that t(8;22)(p11;q11) might define a dual myeloid and B-lymphoid disorder.
Corneal Nerve Architecture in a Donor with Unilateral Epithelial Basement Membrane Dystrophy
Authors: He Jiucheng , Bazan Haydee E.P.
Published: January 2013

Background: Epithelial basement membrane dystrophy (EBMD) is by far the most common corneal dystrophy. In this study, we used a newly developed method of immunofluorescence staining and imaging to study the entire corneal nerve architecture of a donor with unilateral EBMD. Method: Two fresh eyes from a 56-year-old male donor were obtained; the right eye of the donor was diagnosed with EBMD and the left was normal. After slit lamp examination, the corneas were immunostained with anti-β-tubulin III antibody. Images were recorded by a fluorescent microscope equipped with a Photometrics digital camera using MetaVue imaging software. Results: The left cornea appeared normal as observed by slit lamp and stereomicroscope, but the right eye had numerous irregular geographic patches in the basement membrane. Immunofluorescence showed no difference in the stromal nerve distribution between the 2 eyes, but there were areas without innervations in the EBMD cornea. Subbasal nerve fibers also showed tortuous courses and fewer divisions. There was a significant decrease in the density of subbasal nerve fibers and the number of terminals in the right eye. Conclusion: We show for the first time detailed nerve architecture in an EBMD cornea. Our results suggest that EBMD-induced abnormalities of basement membrane altered epithelial nerve architecture and decreased nerve density, contributing to the pathology of the disease.
A Review: Treatment of Alzheimer’s Disease Discovered in Repurposed Agents
Authors: Appleby Brian S. , Nacopoulos Dimitrios , Milano Nicholas , Zhong Kate , Cummings Jeffrey L.
Published: January 2013

Background/Aims: Many compounds that have already been approved for alternate diagnoses have been studied in relation to Alzheimer’s disease (AD). The purpose of this review is to summarize these studies and discuss the rationale and benefits of repurposing drugs for AD treatment. Methods: Studies of drugs related to AD treatment that were relevant to a disease-modifying mechanism of action (MOA) and are already approved by the Food and Drug Administration for non-AD diagnoses were collected from PubMed. Results: Many drugs already approved for the treatment of other diseases have been studied in relation to AD treatment. Numerous drugs with known toxicity profiles have the potential to be repurposed as a treatment for AD. Conclusion: Known MOA, toxicology, and pharmacodynamic profiles would accelerate the process and increase the odds of finding a more timely disease-modifying treatment for AD.
Acute Cerebrovascular Accident after Cisplatin Treatment in a Patient Taking Letrozole
Authors: Digklia Antonia , Voutsadakis Ioannis A.
Published: January 2013

Vascular thrombotic events are common in patients with cancer and chemotherapy is considered a contributing factor. Venous thrombotic events are more common than arterial ones which are less documented. In this report, we describe a patient with right homonymous hemianopsia following treatment with cisplatin for small cell lung carcinoma while also taking letrozole. A brief review of the literature on arterial thrombotic events after chemotherapy follows.
Endoskopische Therapie von Nahtinsuffizienzen des Ösophagus
Authors: Wedemeyer Jochen
Published: January 2013

Hintergrund: Nahtinsuffizienzen stellen eine gefürchtete Komplikation nach Operationen an der Speiseröhre dar, die mit hoher Morbidität und Mortalität vergesellschaftet sind. Methoden: Die Einlage komplett beschichteter Stents stellt die am häufigsten eingesetzte Methode zur Behandlung ösophagealer Leckagen dar. Eine neue endoskopische Therapiemodalität besteht mit der endoskopischen Vakuumschwammtherapie. Hierbei macht man sich die positiven Effekte des vakuumassistierten Verschlusses (Vacuum-Assisted Closure, V.A.C.), der eine etablierte Therapiemodalität zur Behandlung ausgedehnter infizierter Hautdefekte darstellt, zunutze. Durch neue Entwicklungen haben auch Clips (insbesondere der «Over-the-Scope-Clip», OTSC) wieder eine Bedeutung beim Verschluss von ösophagealen Nahtinsuffizienzen erhalten. Ergebnisse: Mit diesen endoskopischen Techniken lassen sich Nahtinsuffizienzen des Ösophagus in über 80% der Fälle erfolgreich verschließen. Schlussfolgerung: Endoskopische Techniken stellen eine geeignete Methode zum Verschluss ösophagealer Leckagen dar und konnten daher in den letzten 10 Jahren die chirurgische Revision weitestgehend verdrängen
Significance of Interdisciplinary Cooperation in the Treatment of Upper Gastrointestinal Mucosal and Submucosal Lesions: A Single Centre Experience
Authors: Stanaitis Juozas , Vaicekauskas Rolandas , Lipnickas Vytautas , Valantinas Jonas , Strupas Kestutis
Published: January 2013

Background: Endoscopic submucosal dissection (ESD) was initially developed in Japan for the treatment of early gastric cancer. Meanwhile ESD has become the treatment of choice for mucosal and submucosal lesions of the oesophagus and stomach. Method: We retrospectively reviewed our data on ESD performed in the period from 2007 to 2011 for the treatment of 67 mucosal and 8 submucosal lesions. These procedures were applied for 60 patients (mean age 63.8 years; 37 female and 23 male). Results: In 4 patients, we found more than 1 lesion for which ESD was applied as a treatment procedure. In 3 patients, ESD was repeated for lesion recurrence in the same location. The ESD specimens were classified as having tumour-free margins in 64 (95.5%) cases; however, during follow-up we identified 7 (10.4%) patients with recurrent lesions, including 3 cases of recurrent hyperplastic polyps, 1 case of early gastric cancer located in the cardia region of the stomach, and 1 case of recurrent flat tubular adenoma in the antral part of the stomach. We experienced 6 cases (8.9%) of delayed post-procedural bleeding all of which were successfully controlled endoscopically. In 5 cases (7.5%), perforation complications occurred. Conclusion: Our first experience with ESD was not all smooth: while the complication rate did not exceed 10%, it was markedly higher than that stated in Eastern literature. We would like to put this down to the learning curve phenomenon. The close cooperation between gastroenterologists and abdominal surgeons was very important and will play a vital role for technological innovations and safety in abdominal medicine in the future.
Genetic Modification of Primate Amniotic Fluid-Derived Stem Cells Produces Pancreatic Progenitor Cells in vitro
Authors: Zhou Yu , Mack David L. , Williams J. Koudy , Mirmalek-Sani Sayed-Hadi , Moorefield Emily , Chun So-Young , Wang Jun , Lorenzetti Diego , Furth Mark , Atala Anthony , Soker Shay
Published: January 2013

Insulin therapy for type 1 diabetes does not prevent serious long-term complications including vascular disease, neuropathy, retinopathy and renal failure. Stem cells, including amniotic fluid-derived stem (AFS) cells - highly expansive, multipotent and nontumorigenic cells - could serve as an appropriate stem cell source for β-cell differentiation. In the current study we tested whether nonhuman primate (nhp)AFS cells ectopically expressing key pancreatic transcription factors were capable of differentiating into a β-cell-like cell phenotype in vitro. nhpAFS cells were obtained from Cynomolgus monkey amniotic fluid by immunomagnetic selection for a CD117 (c-kit)-positive population. RT-PCR for endodermal and pancreatic lineage-specific markers was performed on AFS cells after adenovirally transduced expression of PDX1, NGN3 and MAFA. Expression of MAFA was sufficient to induce insulin mRNA expression in nhpAFS cell lines, whereas a combination of MAFA, PDX1 and NGN3 further induced insulin expression, and also induced the expression of other important endocrine cell genes such as glucagon, NEUROD1, NKX2.2, ISL1 and PCSK2. Higher induction of these and other important pancreatic genes was achieved by growing the triply infected AFS cells in media supplemented with a combination of B27, betacellulin and nicotinamide, as well as culturing the cells on extracellular matrix-coated plates. The expression of pancreatic genes such as NEUROD1, glucagon and insulin progressively decreased with the decline of adenovirally expressed PDX1, NGN3 and MAFA. Together, these experiments suggest that forced expression of pancreatic transcription factors in primate AFS cells induces them towards the pancreatic lineage.
A Pilot Feasibility Study of a Questionnaire to Determine European Union-Wide CAM Use
Authors: Eardley Susan , Bishop Felicity L. , Cardini Francesco , Santos-Rey Koldo , Jong Miek C. , Ursoniu Sorin , Dragan Simona , Hegyi Gabriella , Uehleke Bernhard , Vas Jorge , Jupaneant Ovidiu , Citro Maria Caterina , Fønnebø Vinjar , Quandt Sara A. , Lewith George
Published: January 2013

Background: No questionnaire specifically measuring the core components of complementary and alternative medicine (CAM) use has been validated for use across European Union (EU) countries. We aimed to determine the face validity, acceptability and the participants’ comprehension of a pre-existing questionnaire designed to measure ‘CAM use’, to provide a comparative, standardised questionnaire for use by health care providers, policy makers and purchasers throughout Europe. Methods: Established procedures were employed to translate the questionnaire into 4 EU languages. The translated questionnaires were piloted on 50 healthy adults from each country who may never have used CAM. 10 participants per country also took part in audio-recorded think aloud interviews about the questionnaire. The interviews were transcribed and analysed in the language in which they were conducted; findings were summarised in English. Questionnaire data were pooled across countries, and patterns of completion and missing data were analysed. Results: The questionnaire was translated into Italian, Spanish, Dutch and Romanian. The mean age of the participants was 43.6 years. 34% were male, 87.4% were either light or heavy CAM users, and 12.6% were non-users. Qualitative analysis identified common problems across countries including a ‘hard-to-read’ layout, misunderstood terminology and uncertainty in choosing response options. Quantitative analysis confirmed that a substantial minority of respondents failed to follow questionnaire instructions and that some questions had substantial rates of missing data. Conclusions: The I-CAM-Q has low face validity and low acceptability, and is likely to produce biased estimates of CAM use if applied in England, Romania, Italy, The Netherlands or Spain. Further work is required to develop the layout, terms, some response options and instructions for completion before it can be used across the EU.
Regression Modeling of Allele Frequencies and Testing Hardy Weinberg Equilibrium
Authors: Schaid Daniel J. , Sinnwell Jason P. , Jenkins Gregory D.
Published: January 2013

Background/Aims: Tests for whether observed genotype proportions fit Hardy Weinberg Equilibrium (HWE) are widely used in population genetics analyses, as well as to evaluate quality of genotype data. To date, all methods testing for HWE require subjects to be classified into discrete categories, yet it is becoming clear that the distribution of allele frequencies tends to be smooth over geographic regions. Methods: To evaluate the HWE assumption, we develop new approaches to model allele frequencies as functions of covariates, and use these models to test whether there is residual correlation between the two alleles of subjects; lack of residual correlation supports the null hypothesis of HWE, but conditional on how the covariates influence the allele frequencies. Results: By simulations, we illustrate that a simple statistical test of residual correlation of alleles adequately controls the type I error rate, while maintaining power that is comparable to standard tests for HWE. Conclusion: Our approach can be implemented in standard software, enabling more flexible and powerful ways to evaluate the association of covariates with allele frequencies and whether these associations ‘explain' departures from HWE when the covariates are ignored, opening new strategies to evaluate the quality of genotype data generated by next-generation sequencing assays.
The Cross River Gorillas (Gorilla gorilla diehli) at Mawambi Hills, South-West Cameroon: Habitat Suitability and Vulnerability to Anthropogenic Disturbance
Authors: Etiendem Denis N. , Funwi-Gabga Neba , Tagg Nikki , Hens Luc , Indah Eni K.
Published: January 2013

Only about 300 individuals of the Cross River gorilla (CRG;Gorilla gorilla diehli) survive today. The subspecies is endemic to approximately 12–14 sites at the Cameroon-Nigeria border, and is critically endangered. To understand survival prospects of the CRG at Mawambi Hills, Cameroon, a maximum entropy (MaxEnt) distribution model was used to predict the distribution of gorillas. Overall, 24% of the study area was predicted to be suitable for gorillas. The most important predictors of gorilla distribution were elevation as a surrogate for accessibility (52.4%), distance to nearby villages which represents proximity to anthropogenic disturbance (22.7%), and slope steepness as a proxy for security (19.4%). Gorillas mainly occupied slopes of steep hills and avoided areas of human disturbance. To evaluate the spatial relationship between gorilla distribution and human activities, the predicted habitat suitability map was overlaid with a kernel density map of human activities. A positive correlation was found between locations of human activity and suitable habitat for gorillas (r = 0.5). This suggests that anthropogenic pressures in previously unused forest areas are increasing as a result of resource depletion at lower altitudes, consequently putting the gorillas at greater risk. Conservation management plans that seek to reduce human encroachment into habitats preferred by gorillas such as steep hills will probably contribute to gorilla survival.