bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast Growth of Infants of Overweight Mothers: Can It Be Slowed Down
Authors: Haschke Ferdinand , Ziegler Ekhard E. , Grathwohl Dominik
Published: July 2014

Data from 3 recently completed studies were pooled and analyzed to answer the question whether breastfed infants of overweight/obese mothers show accelerated growth. It was shown that these infants gain weight faster than indicated by the WHO standards and that they grow significantly faster than infants of lean mothers. The question whether fast infant growth can be slowed down by lowering the protein content of formulas was examined. It was shown that formulas with a protein content that is just moderately above that of human milk support normal growth while significantly slowing down fast growth.
Developmental Programming and Transgenerational Transmission of Obesity
Authors: Vickers M.H.
Published: July 2014

The global obesity pandemic is often causally linked to marked changes in diet and lifestyle, namely marked increases in dietary intakes of high-energy diets and concomitant reductions in physical activity levels. However, far less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from environmental perturbations during the early-life period. Human and animal studies have highlighted the link between alterations in the early-life environment and increased susceptibility to obesity and related metabolic disorders in later life. In particular, altered maternal nutrition, including both undernutrition and maternal obesity, has been shown to lead to transgenerational transmission of metabolic disorders. This association has been conceptualised as the developmental programming hypothesis whereby the impact of environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the physiology of the offspring. Further, evidence to date suggests that this developmental programming is a transgenerational phenomenon, with a number of studies showing transmission of programming effects to subsequent generations, even in the absence of continued environmental stressors, thus perpetuating a cycle of obesity and metabolic disorders. The mechanisms responsible for these transgenerational effects remain poorly understood; evidence to date suggests a number of potential mechanisms underpinning the transgenerational transmission of the developmentally programmed phenotype through both the maternal and paternal lineage. Transgenerational phenotype transmission is often seen as a form of epigenetic inheritance with evidence showing both germline and somatic inheritance of epigenetic modifications leading to phenotype changes across generations. However, there is also evidence for non-genomic components as well as an interaction between the developing fetus with the in utero environment in the perpetuation of programmed phenotypes. A better understanding of how developmental programming effects are transmitted is essential for the implementation of initiatives aimed at curbing the current obesity crisis.
Developmental Programming of Appetite/Satiety
Authors: Ross Michael G. , Desai Mina
Published: July 2014

Obesity is often attributed to a Western lifestyle, a high-fat diet and decreased activity. While these factors certainly contribute to adult obesity, compelling data from our laboratory and others indicate that this explanation is oversimplified. Recent studies strongly argue that maternal/fetal under- or overnutrition predisposes the offspring to become hyperphagic and increases the risk of later obesity. Both infants small for gestational age (SGA) or infants born to obese mothers who consume a high-fat diet are at a markedly increased risk of adult obesity. Specific alterations in the fetal metabolic/energy environment directly influence the development of appetite regulatory pathways. Specifically, SGA infants demonstrate (1) impaired satiety and anorexigenic cell signaling, (2) enhanced cellular orexigenic responses, (3) programmed dysfunction of neuroprogenitor cell proliferation/differentiation, and (4) increased expression of appetite (NPY) versus satiety (POMC) neurons. In both hypothalamic tissue and ex vivo culture, SGA newborns exhibit increased levels of the nutrient sensor SIRT1, signifying reduced energy, whereas maternal high-fat-exposed newborns exhibit reduced levels of pAMPK, signifying energy excess. Via downstream regulation of bHLH neuroproliferation (Hes1) and neurodifferentiation factors (Mash1, Ngn3), neurogenesis is biased toward orexigenic and away from anorexigenic neurons, resulting in excess appetite, reduced satiety and development of obesity. Despite the developmental programming of appetite neurogenesis, the potential for neuronal remodeling raises the opportunity for novel interventions.
Tocilizumab-Induced Psoriasiform Rash in Rheumatoid Arthritis
Authors: Palmou-Fontana Natalia , Sánchez Gaviño Juan Antonio , McGonagle Dennis , García-Martinez Eva , Iñiguez de Onzoño Martín Luis
Published: July 2014

Tocilizumab (TCZ) is a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor and has been approved for the treatment of rheumatoid arthritis (RA) patients who have had an inadequate response to previous biological therapies. Psoriasiform skin lesions, especially palmoplantar pustulosis lesions, are well described following anti-tumour necrosis factor therapy. We describe a 79-year-old woman with rheumatoid factor-positive, anti-citrullinated protein antibody-positive erosive RA, who developed a psoriasiform palmoplantar pustulosis reaction following treatment with TCZ therapy (IL-6 receptor). The rash showed histological features compatible with psoriasis and disappeared following discontinuation of TCZ.
Intravitreal Functional Plasminogen in Eyes with Branch Retinal Vein Occlusion
Authors: Bertelmann Thomas , Sekundo Walter , Strodthoff Stefan , Witteborn Michael C.P. , Stief Thomas , Irle Sebastian , Nguyen Nauke , Koss Michael J. , Mennel Stefan
Published: July 2014

Purpose: To evaluate whether intravitreal functional plasminogen is elevated in eyes with branch retinal vein occlusion (BRVO) and to discover whether intravitreal plasminogen activities are correlated with the extent of blood-retina barrier (BRB) breakdown. Methods: Our study is a prospective case series of 20 consecutive patients with BRVO and 10 consecutive patients serving as controls. Vitreous taps were extracted from the central vitreous body and plasminogen was functionally determined in an innovative, ultrasensitive p-nitroanilide reaction after activation with streptokinase (100% of normal, %N = functional plasminogen in pooled normal citrated plasma). Intravitreal VEGF levels were assayed to estimate BRB breakdown. Results: Intravitreal functional plasminogen was detected in all analyzed samples (n = 30) and mean (±SD) plasminogen activities were found to be 0.97 ± 1.06%N (range: 0.03-3.9%N). Patients suffering from BRVO exhibited significantly higher intravitreal plasminogen (1.35 ± 1.11%N) in comparison with controls (0.20 ± 0.21%N, p < 0.001). Intravitreal VEGF concentrations in the BRVO group (576 ± 547 pg/ml) were significantly higher than these in controls (111 ± 120 pg/ml, p = 0.003). There was a significant correlation between intravitreal functional plasminogen and intravitreal VEGF levels (r = 0.519, p = 0.003). Conclusions: Intravitreal functional plasminogen is significantly elevated in eyes suffering from BRVO and correlates with the extent of BRB breakdown. The induction of posterior vitreous detachment by using intravitreally administered recombinant tissue plasminogen activator (enzymatic vitreolysis) should be explored in further investigations.
Detection of Fovea-Threatening Diabetic Macular Edema by Optical Coherence Tomography to Maintain Good Vision by Prophylactic Treatment
Authors: Hirano Takao , Iesato Yasuhiro , Toriyama Yuichi , Imai Akira , Murata Toshinori
Published: July 2014

Background/Aims: To establish a screening and treatment method for fovea-threatening diabetic macular edema (DME) using spectral-domain optical coherence tomography (SD-OCT). In order to maintain good visual acuity (VA), focal/grid laser treatment for screened fovea-threatening DME was evaluated based on macular thickness map images produced by SD-OCT. Methods: In 66 diabetic eyes with no visual deterioration, the sensitivity and the specificity of SD-OCT without the use of mydriatics for the detection of fovea-threatening DME were determined. A definite diagnosis of DME was made under mydriasis, using slitlamp biomicroscopy with a contact lens. Eyes with fovea-threatening DME then underwent prophylactic focal/grid laser treatment. The main outcome measures were corrected VA and central macular thickness (CMT). Results: A definitive diagnosis of DME was made in 5 of the 66 eyes, while macular thickening above the 99th percentile was detected in 11 (Cirrus®) or 13 (RS-3000®) eyes by SD-OCT. The focal/grid laser treatment of the 5 eyes with fovea-threatening DME successfully maintained good VA, which was 0.91 ± 0.76 (average: 20/22; 0.04 ± 0.12 logMAR) before treatment and 0.89 ± 0.70 (average: 20/22; 0.05 ± 0.15 logMAR; p = 0.88) 1 year afterwards. The average CMT was stable before and after focal/grid lasering at 302 ± 29 and 329 ± 55 µm, respectively (p = 0.99). Conclusions: The detection of fovea-threatening DME is feasible by SD-OCT without using mydriatics. Prophylactic treatment, such as with focal/grid lasers, was effective in maintaining good VA by avoiding an otherwise highly likely foveal involvement.
Transmission of Obesity-Adiposity and Related Disorders from the Mother to the Baby
Authors: Yajnik Chittaranjan S.
Published: July 2014

The conventional aetiological model of obesity and diabetes proposes a genetic predisposition and a precipitation by an unhealthy adult lifestyle. This hypothesis was challenged by David Barker who proposed that the intrauterine environment influences the risk of non-communicable diseases (NCDs). The original idea was based on fetal undernutrition because lower birth weight was associated with a higher risk of diabetes and heart disease. However, soon it was clear that the association was U shaped, and that the increased risk in large babies was driven by maternal obesity and diabetes. A number of human and animal studies have refined our ideas of ‘fetal programming', which is now thought to be related to acquired chemical changes in DNA (methylation), histones (acetylation and other) and the role of non-coding miRNAs. Maternal nutritional disturbances are the major programming stimulus, in addition to a deranged metabolism, infections, maternal stress, extreme atmospheric temperature, etc. The first demonstration of a link between fetal ‘starvation' and future ill-health was in the Dutch Hunger Winter studies. In the prospective Pune Maternal Nutrition Study, we found that small and thin Indian babies were more adipose compared to larger English babies, and their higher risk of future diabetes was reflected in higher insulin and leptin and lower adiponectin concentrations in the cord blood. This phenotype was partly related to a deranged 1-carbon metabolism due to an imbalance in vitamin B12 (low) and folate (high) nutrition, which was also related to insulin resistance in the offspring. Maternal obesity and diabetes have made an increasing contribution to childhood obesity and diabetes at a young age. This was prominently shown in Pima Indians but is now obvious in all other populations. The best window of opportunity to prevent fetal programming of NCDs is in the periconceptional period. This is the period when gametogenesis, fertilisation, implantation, embryogenesis and placentation occur. Improving the nutrition and the health of young girls could make a substantial contribution to reducing the rapidly rising epidemic of NCDs in the world. This is referred to as ‘primordial' prevention.
Incidence of Cardioembolic Stroke Including Paradoxical Brain Embolism in Patients with Acute Ischemic Stroke before and after the Great East Japan Earthquake
Authors: Itabashi Ryo , Furui Eisuke , Sato Shoichiro , Yazawa Yukako , Kawata Kenta , Mori Etsuro
Published: July 2014

Background: The incidence of heart disease or deep vein thrombosis (DVT) reportedly increased after the Great East Japan Earthquake. We hypothesized that the incidence of cardioembolic stroke (CES) including paradoxical brain embolism (PBE) among patients with acute stroke would increase after the earthquake due to cessation of antithrombotic therapy or the increase in heart disease and DVT associated with the evacuation. The aim of this study is to evaluate the changes in the prevalence of DVT and the incidence of CES including PBE in acute ischemic stroke before and after the earthquake. Methods: We retrospectively studied 1,044 consecutive ischemic stroke patients (73.1 ± 12.5 years old, male 61.5%) who were admitted to a comprehensive stroke center (from January 2010 through March 2012) located in the earthquake disaster area within 7 days after stroke onset. The prevalence of DVT and the incidence of CES including PBE were compared before and after the earthquake of 11 March 2011. Results: The median of the initial National Institutes of Health Stroke Scale (NIHSS) scores was 4 (interquartile range: 1-8). Two hundred and eighty-two patients (27.0% of those surveyed) were diagnosed with CES. After adjustment for sex, age, NIHSS score, and patient's residential address, the proportion of CES patients was significantly increased after the earthquake (odds ratio, OR 1.61, 95% confidence interval, 95% CI: 1.20-2.17). Eighty-nine patients (8.5% of those surveyed) had DVT. Compared with 2010 findings, the prevalence of DVT was significantly increased in the fourth quarter of 2011 and the first quarter of 2012 (OR 1.85, 95% CI: 1.05-3.24). Nineteen (1.8% of those surveyed) were diagnosed with PBE. The proportion of PBE patients was also significantly increased in the second half of 2011 (OR 3.69, 95% CI: 1.28-12.1). Conclusions: The incidence of CES was significantly increased after the earthquake, compared with the period before the earthquake. We encountered more PBE in the period from 3 to 9 months after the earthquake and found more DVT in the acute ischemic stroke patients in the period from 6 through 12 months after the earthquake. In these types of disasters, we have to ensure the distribution of drugs, including antithrombotics, and support the prevention of DVT in the refugees.
Predictors of Postoperative Complications, Prolonged Length of Hospital Stay, and Short-Term Mortality in Elderly Patients with Malignant Head and Neck Neoplasm
Authors: Gerude Maurício Freitas , Dias Fernando Luiz , de Farias Terence Pires , Albuquerque Sousa Bruno , Thuler Luiz Cláudio S.
Published: July 2014

Purpose: To identify and assess predictors of short-term outcomes and a prolonged length of hospital stay after head and neck cancer surgery in older-old and oldest-old patients. Procedures: Patients aged ≥75 years with head and neck cancer undergoing surgery at the Brazilian National Cancer Institute from January to December 2011 were assessed regarding postoperative complications, mortality, and length of hospital stay. Results: Over the study period, 67 patients with head and neck cancer underwent surgery, 44.8% of whom developed complications within 30 days of surgery, surgical site and respiratory infections (29.9 and 20.9%, respectively) being the most common. The mean length of hospital stay was 7 days (range: 2-26). In multivariate analysis, previous radiotherapy, dependence in instrumental activities of daily living, and low serum hemoglobin (≤13.2 g/dl) were predictors of complications. In addition, the presence of at least 1 clinical or surgical complication, smoking, and an arm circumference ≤25 cm were independent predictors of a prolonged length of hospital stay. Conclusions: Complications after head and neck cancer surgery in the elderly are common and related to the prolonged length of hospital stay, both being influenced by previous radiotherapy, smoking, functional dependence in instrumental activities of daily living, and nutritional conditions. Such predictors should be considered in a preoperative assessment of elderly patients as these are modifiable risk factors.
Ropivacaine for Continuous Wound Infusion for Postoperative Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Raines Shane , Hedlund Cecilia , Franzon Malin , Lillieborg Stefan , Kelleher Glen , Ahlén Kjell
Published: July 2014

Background: The use of continuous wound infusion (CWI) of local anaesthetics has been suggested as a safe and effective alternative technique to epidural anaesthesia/analgesia that allows surgeons to provide postoperative pain relief while reducing opioid consumption and associated adverse events. A previous meta-analysis by Liu et al. [Am Coll Surg 2006;203:914-932] reported results mainly from studies of bupivacaine. Subsequently, several new randomized controlled trials (RCTs) of ropivacaine have been published. This systematic review and quantitative meta-analysis evaluates the efficacy of ropivacaine for CWI. Methods: Systematic literature searches (EMBASE, MEDLINE) were performed to retrieve studies which met the following criteria: double-blind RCT of ropivacaine versus either placebo or an active comparator; use of ropivacaine solution without added active agents, and prohibition of other routine analgesics during the study period except rescue patient-controlled analgesia. For each included study, standardized effect sizes for ropivacaine versus placebo were calculated for opioid rescue use, pain score at rest, and pain score at mobilization. Meta-analyses were conducted for each endpoint. Results: Fourteen RCTs comparing ropivacaine (n = 376) versus placebo (n = 380) were identified. Effect size estimates revealed significantly less opioid rescue use for ropivacaine patients (-1.3; 95% CI -1.5 to -1.1) and significantly less pain for ropivacaine patients both at rest (-1.1; 95% CI -1.3 to -0.9) and on mobilization (-1.5; 95% CI -1.7 to -1.3). The weighted mean reduction in opioid rescue use was 22.4 mg. Conclusion: This systematic review and meta-analysis presents substantial evidence that ropivacaine provides clinically meaningful reductions in opioid use and pain outcomes. Ropivacaine CWI is effective for postoperative pain management in a wide range of surgical procedures.
Plasma Natriuretic Peptides and Incidence of Subtypes of Ischemic Stroke
Authors: Berntsson John , Zia Elisabet , Borné Yan , Melander Olle , Hedblad Bo , Engström Gunnar
Published: July 2014

Background and Purpose: Natriuretic peptides predict poor outcomes in cardiovascular disease. However, the knowledge of their relationship to stroke is limited and prospective studies from the general population are few. The purpose of this study was to explore the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and midregional pro-atrial natriuretic peptide (MR-proANP) plasma levels and the risk for ischemic stroke and its subtypes. Methods: NT-proBNP and MR-proANP were measured in fasting blood samples from 4,862 subjects (40.2% men, mean age 57.5 ± 6.0 years) without cardiovascular disease from the Malmö Diet and Cancer Study, a prospective, population-based study in Sweden. Incidence of ischemic stroke was monitored over a mean follow-up of 14.9 ± 3.0 years. Stroke cases were etiologically classified according to the TOAST classification. Cox proportional-hazards regression was used to study the incidence of stroke in relationship to NT-proBNP and MR-proANP. Results: During follow-up, 227 had a first-ever ischemic stroke (large-artery atherosclerosis, n = 35; cardioembolic stroke, n = 44; small-artery occlusion, n = 80; undetermined cause, n = 68). In the age- and sex-adjusted model, only NT-proBNP was associated with total ischemic stroke. This association was completely explained by an increased incidence of cardioembolic stroke. Adjusted for cardiovascular risk factors (age, sex, hypertension, diabetes, smoking, body mass index and low-density lipoprotein cholesterol), the hazard ratios (HRs, 95% confidence interval, 95% CI) for cardioembolic stroke were 1.00 (reference), 1.42 (0.34-6.00), 2.79 (0.77-10.12) and 5.64 (1.66-19.20), respectively, for the 1st, 2nd, 3rd and 4th quartiles of NT-proBNP. The corresponding HRs (95% CIs) for quartiles of MR-proANP were 1.00 (reference), 1.83 (0.55-6.14), 1.20 (0.33-4.34) and 3.96 (1.31-11.99), respectively. In total, 335 (6.9%) subjects were diagnosed with atrial fibrillation during follow-up. Among the cardioembolic stroke cases, 30% were diagnosed with atrial fibrillation before the stroke event and another 36% within 6 months after the stroke. Of the cardioembolic stroke cases with atrial fibrillation, 59% were in the top quartile of NT-proBNP, 69% in the top quartile of MR-proANP and 79% were either in the top quartile of NT-proBNP or in the top quartile of MR-proANP. Conclusion: High plasma levels of NT-proBNP and MR-proANP are associated with a substantially increased risk of cardioembolic stroke, but not with other subtypes of ischemic stroke. The results suggest that assessment of stroke risk, including electrocardiography, is warranted in subjects with high NT-proBNP or MR-proANP.
Persistence and Prognostic Implications of Orthostatic Hypotension in Older Individuals with Mild-to-Moderate Dementia
Authors: Soennesyn Hogne , Dalen Ingvild , Aarsland Dag
Published: July 2014

Aim: To study the course and prognostic implications of orthostatic hypotension (OH) in older individuals with mild-to-moderate dementia. Methods: Referrals to outpatient clinics specialising in old age psychiatry and geriatric medicine in the counties of Rogaland and Hordaland in western Norway with a first-time diagnosis of mild dementia were consecutively asked for inclusion. A total of 211 participants underwent a comprehensive baseline assessment with annual follow-ups. Patients with OH at both baseline and the 1-year follow-up were classified as having persistent OH. Outcome measures were the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating sum of boxes (CDR-SB), and time to death. Results: From baseline to the 4-year follow-up, 30-45% of the participants had OH at each follow-up. In multivariable analysis, persistent OH was not significantly associated with either the longitudinal course of MMSE or CDR-SB scores or survival. Conclusions: OH was moderately prevalent over 4 years in older individuals with mild dementia, and persistent OH did not predict either cognitive or functional decline or survival.
Renal AA Amyloidosis in Patients with Type 2 Diabetes Mellitus
Authors: Díez Ramón , Madero Magdalena , Gamba Gerardo , Soriano Juan , Soto Virgilia
Published: July 2014

Background: Type 2 diabetes mellitus (T2DM) is the leading cause of chronic kidney disease and a major cause of cardiovascular disease (CVD) mortality. Inflammation is closely involved in the pathogenesis of T2DM, and reactive amyloidosis occurs in the presence of chronic inflammation. We hypothesized that patients with T2DM may have a higher prevalence of renal AA amyloidosis (RAAA) and that this could contribute to worse atherosclerosis and CVD. Materials and Methods: We analyzed 330 autopsy kidneys from patients with a previous T2DM diagnosis. The kidney tissue was evaluated in order to determine the presence of diabetic nephropathy and RAAA, and systemic vessels were evaluated for the presence of atherosclerosis. Results: RAAA was detected in 9% of our study population and was associated with an increased risk for nodular sclerosis [OR (95% CI)] [11 (2.04-59.16)], for chronic ischemic cardiomyopathy [4.59 (2.02-10.42)], for myocardial infarction [3.41 (1.52-7.64)] as well as for aortic [4.75 (1.09-20.69)], coronary [3.22 (1.47-7.04)], and intrarenal atherosclerosis [3.84 (1.46-10.09)]. Conclusions: RAAA is prevalent in T2DM and is associated with worse CVD and renal disease, likely because RAAA is a marker of severe chronic inflammation.
The Role of Echocardiography in the Intraoperative Management of the Fetus Undergoing Myelomeningocele Repair
Authors: Rychik Jack , Cohen David , Tran Kha M. , Szwast Anita , Natarajan Shobha S. , Johnson Mark P. , Moldenhauer Julie S. , Khalek Nahla , Martinez-Poyer Juan , Flake Alan W. , Hedrick Holly L. , Adzick N. Scott
Published: July 2014

Introduction: Fetal surgery for myelomeningocele (MMC) results in better outcomes compared to postnatal treatment. However, risks are present. We describe our experience with intraoperative fetal echocardiography during repair of MMC and report on the management of serious cardiovascular events. Material and Methods: The subjects included fetuses with intent to repair MMC from January 2011 to February 2014. The protocol involved continuous echocardiography in a looping, sequential manner of systolic function, heart rate and tricuspid and mitral valve regurgitation. Results: A total of 101 cases intended fetal MMC repair; 100 completed surgery. Intraoperative ventricular dysfunction was present in 60% (20 mild, 25 moderate, 15 severe). Heart rate <100 bpm was noted in 11 cases. Tricuspid valve regurgitation was present in 35% (26 mild, 7 moderate, 2 severe); mitral valve regurgitation was present in 19% (15 mild, 4 moderate). Serious cardiovascular events were experienced in 7 cases, which affected the conduct of surgery and/or outcome. In 4 of these, medications were given via the umbilical vein and external cardiac compressions were performed. Fetal echocardiography was used to gauge the efficacy of compressions and to guide resuscitation. Discussion: Cardiovascular compromise is common during fetal surgery for MMC. Intraoperative fetal echocardiography is recommended as a growing number of centers contemplate offering this form of novel, but potentially risky, therapy.
Glycyrrhizic Acid Ameliorates HMGB1-Mediated Cell Death and Inflammation after Renal Ischemia Reperfusion Injury
Authors: Lau Arthur , Wang Shuang , Liu Weihua , Haig Aaron , Zhang Zhu-Xu , Jevnikar Anthony M.
Published: July 2014

Background: Renal ischemia reperfusion injury (IRI) leads to acute kidney injury (AKI) and the death of tubular epithelial cells (TEC). The release of high-mobility group box-1 (HMGB1) and other damage-associated molecular pattern moieties from dying cells may promote organ dysfunction and inflammation by effects on TEC. Glycyrrhizic acid (GZA) is a functional inhibitor of HMGB1, but its ability to attenuate the HMGB1-mediated injury of TEC has not been tested. Methods/Results: In vitro, hypoxia and cytokine treatment killed TEC and resulted in the progressive release of HMGB1 into the supernatant. GZA reduced the hypoxia-induced TEC death as measured by annexin-V and propidium iodide. Hypoxia increased the expression of MCP-1 and CXCL1 in TEC, which was reduced by GZA in a dose-dependent manner. Similarly, the HMGB1 activation of effector NK cells was inhibited by GZA. To test the effect of HMGB1 neutralization by GZA in vivo, mice were subjected to renal IRI. HMGB1 protein expression increased progressively in kidneys from 4 to 24 h after ischemia and was detected in tubular cells by 4 h using immunohistochemistry. GZA preserved renal function after IRI and reduced tubular necrosis and neutrophil infiltration by histological analyses and ethidium homodimer staining. Conclusions: Importantly, these data demonstrate for the first time that AKI following hypoxia and renal IRI may be promoted by HMGB1 release, which can reduce the survival of TEC and augment inflammation. Inhibition of the interaction of HMGB1 with TEC through GZA may represent a therapeutic strategy for the attenuation of renal injury following IRI and transplantation.
RNA Polymerase II Forms Transcription Networks in Rye and Arabidopsis Nuclei and Its Amount Increases with Endopolyploidy
Authors: Schubert Veit
Published: July 2014

RNA polymerase II (RNAPII) is responsible for the transcription of most eukaryotic genes. In mammalian nuclei, RNAPII is mainly localized in relatively few distinct transcription factories. In this study - applying super-resolution microscopy - it is shown that in plants, inactive (non-phosphorylated) and active (phosphorylated) RNAPII modifications compose distinct ‘transcription networks' within the euchromatin. These reticulate structures sometimes attach to each other, but they are absent from heterochromatin and nucleoli. The global RNAPII distribution within nuclei is not influenced by interphase chromatin organization such as Rabl (rye) versus non-Rabl (Arabidopsis thaliana) orientation. Replication of sister chromatids without cell division causes endopolyploidy, a phenomenon widespread in plants and animals. Endopolyploidy raises the number of gene copies per nucleus. Here, it is shown that the amounts of active and inactive RNAPII enzymes in differentiated 2-32C leaf nuclei of A. thaliana proportionally increase with rising endopolyploidy. Thus, increasing the transcriptional activity of cells and tissues seems to be an important function of endopolyploidy.
Changes in Histone Methylation and Acetylation during Microspore Reprogramming to Embryogenesis Occur Concomitantly with BnHKMT and BnHAT Expression and Are Associated with Cell Totipotency, Proliferation, and Differentiation in Brassica napus
Authors: Rodríguez-Sanz Héctor , Moreno-Romero Jordi , Solís María-Teresa , Köhler Claudia , Risueño María C. , Testillano Pilar S.
Published: July 2014

In response to stress treatments, microspores can be reprogrammed to become totipotent cells that follow an embryogenic pathway producing haploid and double-haploid embryos which are important biotechnological tools in plant breeding. Recent studies have revealed the involvement of DNA methylation in regulating this process, but no information is available on the role of histone modifications in microspore embryogenesis. Histone modifications are major epigenetic marks controlling gene expression during plant development and in response to environmental changes. Lysine methylation of histones, accomplished by histone lysine methyltransferases (HKMTs), can occur on different lysine residues, with histone H3K9 methylation being mainly associated with transcriptionally silenced regions. In contrast, histone H3 and H4 acetylation is carried out by histone acetyltransferases (HATs) and is associated with actively transcribed genes. In this work, we analyzed 3 different histone epigenetic marks: dimethylation of H3K9 (H3K9me2) and acetylation of H3 and H4 (H3Ac and H4Ac) during microspore embryogenesis in Brassica napus by Western blot and immunofluorescence assays. The expression patterns of histone methyltransferase BnHKMT and histone acetyltransferase BnHAT genes have also been analyzed by qPCR. Our results revealed different spatial and temporal distribution patterns for methylated and acetylated histone variants during microspore embryogenesis and their similarity with the expression profiles of BnHKMT and BnHAT, respectively. The data presented suggest the participation of H3K9me2 and HKMT in embryo cell differentiation and heterochromatinization events, whereas H3Ac, H4Ac, and HAT would be involved in transcriptional activation, totipotency, and proliferation events during cell reprogramming and embryo development.
Chronic Pancreatitis and Pancreatic Cancer
Authors: Kong Xiangyu , Sun Tao , Kong Fanyang , Du Yiqi , Li Zhaoshen
Published: July 2014

Background: Pancreatic cancer (PC) is one of the most lethal diseases with an incidence rate almost equal to the rate of mortality. Chronic pancreatitis (CP) is a common chronic inflammatory disease of unknown etiology that affects the pancreas. Epidemiological studies have identified CP to be a major risk factor for PC. Summary: A greater understanding of the molecular mechanisms linking CP and PC has identified several common pathways that provide targets for future interventions. This article reviews those components in the CP-PC connection, including the role of macrophages, the maintenance of genome stability, cytokines, and other nodal factors such as nuclear factor kappa B, COX-2 and reactive oxygen species. Key Message: The molecular mechanisms that underlie CP and PC provide novel targets for future therapies for PC. Practical Implications: The stromal-desmoplastic reaction plays an important role in initiating and sustaining chronic inflammation and tumor progression. Recently, two targeted anti-tumor agents, erlotinib and nab-paclitaxel, have shown promising therapeutic efficacy. Notably, both these agents target components (EGFR and SPARC) within the inflammatory stroma surrounding malignant cells, underscoring the importance of inflammation in pancreatic carcinogenesis. Identifying the common pathways linking CP and PC may help uncover additional novel targets for future therapies.
Proteomic Analysis of Barley Cell Nuclei Purified by Flow Sorting
Authors: Petrovská Beáta , Jeřábková Hana , Chamrád Ivo , Vrána Jan , Lenobel René , Uřinovská Jana , Šebela Marek , Doležel Jaroslav
Published: July 2014

Many proteins are present in the nucleus; some are involved with its structural and functional organization, some with gene expression, and some with cell division. The plant nuclear proteome has not been well explored. Its characterization requires extraction methods which minimize both the artifactual alteration of the proteins and the extent of contamination with non-nuclear proteins. The conventional multi-step fractionation procedure is both laborious and prone to contamination. Here, we describe a single-step method based on flow sorting. The method allows the separation of G1, S and G2 phase nuclei and minimizes the risk of contamination by non-nuclear proteins. Preliminary results obtained using G1 phase cell nuclei from barley root tips indicate that flow sorting coupled with a protein/peptide separation and mass spectrometry will permit a comprehensive characterization of the plant nuclear proteome.
Endodrainage, Tumor Photocoagulation, and Silicone Oil Tamponade for Primary Exudative Retinal Detachment due to Choroidal Melanoma Persisting after Proton Beam Therapy
Authors: Seibel Ira , Cordini Dino , Willerding Gregor , Riechardt Aline Isabel , Joussen Antonia Maria
Published: July 2014

Background: Choroidal melanoma is frequently accompanied by an exudative retinal detachment that can persist after proton beam therapy. This study investigates whether vitrectomy without tumor resection improves the clinical outcome. Methods: This is a retrospective interventional case series. Twenty patients with choroidal melanoma with exudative retinal detachment involving the macula were treated by vitrectomy, endodrainage, photocoagulation, and silicone oil tamponade after proton beam therapy. Results: The mean follow-up was 38.4 months (median 21.5, range 12.0-122.0). The mean time between proton beam therapy and surgery was 4.5 months (range 0.1-9.2). Reattachment was achieved in 95% of the patients after one vitrectomy. One patient was lost to follow-up because enucleation was performed after 45.9 months due to a secondary glaucoma. Mean visual acuity decreased from 1.1 to 1.8 logMAR before vitrectomy and after 4 years, respectively. No patient showed local tumor recurrence. Metastatic disease was present in 1 patient after 15.2 months, and this patient died after 19.2 months. Conclusion: Vitrectomy is indicated after therapeutic proton beam irradiation in patients who present with persisting exudative retinal detachment involving the macula and high local or systemic risk factors for hemorrhagic complications, thus excluding endoresection.
Severe Liver Damage and Nonallergic Bronchitis with Eosinophilia in a Patient with Follicular Lymphoma Treated with Bendamustine plus Rituximab
Authors: Jo Tatsuro , Horio Kensuke
Published: July 2014

A 66-year-old female with follicular lymphoma developed severe liver dysfunction and nonallergic bronchitis after 1 cycle of treatment with bendamustine and rituximab (BR) therapy. Simultaneously, eosinophilia was observed. Further examination revealed negative results for both hepatitis virus-induced liver damage and lymphoma cell invasion into the liver. No bacterial, fungal, or cytomegaloviral infections of the respiratory tract were observed. The patient was treated with steroid pulse therapy followed by prednisolone with complete resolution of her symptoms. This suggests that eosinophilia induced by the treatment with BR may result in liver dysfunction and nonallergic bronchitis.
Metastatic Urothelial Carcinoma of the Prepuce and Glans Penis: Suspected Implantation of Non-Muscle-Invasive Bladder Cancer via Urine
Authors: Makino Tomoyuki , Kitagawa Yasuhide , Namiki Mikio
Published: July 2014

Cutaneous metastatic implantation of non-muscle-invasive urothelial carcinoma via urine is a rare finding, and only few cases have been reported in the literature. Here, we present a case of metastatic urothelial carcinoma of the prepuce and glans penis, which was suspected to be an implantation of non-muscle-invasive bladder cancer via urine. The patient had pseudophimosis of the penis, and contact with urine containing urothelial carcinoma cells was considered to be the cause of the metastatic implantation.
Green Nail Syndrome (Pseudomonas aeruginosa Nail Infection): Two Cases Successfully Treated with Topical Nadifloxacin, an Acne Medication
Authors: Müller Simon , Ebnöther Myriam , Itin Peter
Published: July 2014

Green nail syndrome (GNS) caused by Pseudomonas aeruginosa is the most common bacterial nail infection. The treatment of GNS is challenging in many cases and recommendations based on clinical trials are lacking. We report two cases with GNS successfully treated with off-label use of topical nadifloxacin, a fluoroquinolone approved for acne and bacterial skin infections in some countries.
TEATRO, PÚBLICO E ESPACIALIDADE: uma discussão do cotidiano
Authors: Perez Shirlei Torres
Published: July 2014

Este trabalho busca discutir a experiência do espectador do ponto de vista da comunicação, partindo da espacialidade como mediação para a percepção de relações cotidianas, em cena e na vida corrente. Em dois espetáculos distintos – Braakland–Terra Esquecida, da Cie Dakar, da Holanda, e Os Efêmeros, do Théâtre du Soleil, da França – poética e espacialidade oportunizam diferentes construções sígnicas a partir dos deslocamentos propostos nessa relação.
Inflammatory Bowel Disease Is Associated With an Increased Risk of Hospitalization for Heart Failure
Authors: Kristensen Søren Lund , Ahlehoff Ole , Lindhardsen Jesper , Erichsen Rune , Lamberts Morten , Khalid Usman , Nielsen Ole Haagen , Torp-Pedersen Christian , Gislason Gunnar Hilmar , Hansen Peter Riis
Published: July 2014

Background—

Inflammatory bowel disease (IBD) has been linked to adverse cardiovascular events, but a relation to heart failure (HF) is uncertain. We investigated the IBD-associated risk of HF in a nationwide setting.

Methods and Results—

A total of 5 436 647 Danish citizens, with no history of IBD or HF, were included on January 1, 1997, and followed up until first hospitalization for HF, death, or December 31, 2011. Of these subjects, 23 681 developed IBD for which disease activity was determined continuously throughout the study. The risk of hospitalization for HF was estimated with a Poisson regression model adjusting for comorbidity and cardiovascular pharmacotherapy as time-dependent covariates. During a mean follow-up of 11.8 years in the reference population and 6.4 years in the IBD group, hospitalization for HF occurred in 553 subjects with IBD and 171 405 in the reference population. Patients with IBD had a 37% increased risk of hospitalization for HF (incidence rate ratio, 1.37; 95% confidence interval, 1.26–1.49) compared with the reference population. IBD activity-specific analyses showed markedly increased risk of HF hospitalization during flares (incidence rate ratio, 2.54; 95% confidence interval, 2.13–3.04) and persistent activity (incidence rate ratio, 2.73; 95% confidence interval, 2.25–3.33) but not in IBD remission (incidence rate ratio, 1.04; 95% confidence interval, 0.94–1.16).

Conclusions—

In a nationwide cohort, IBD was associated with an increased risk of hospitalization for HF, and this risk was strongly correlated to periods of active disease. The mechanisms underlying this finding warrant further studies.
Pathogenetical Subtypes of Recurrent Intracerebral Hemorrhage
Authors: Yeh Shin-Joe , Tang Sung-Chun , Tsai Li-Kai , Jeng Jiann-Shing
Published: July 2014

Background and Purpose—

Pathogenetic classification of intracerebral hemorrhage (ICH), using systems such as SMASH-U (structural vascular lesions, medication, cerebral amyloid angiopathy [CAA], systemic disease, hypertension, or undetermined), is important in predicting functional outcomes and mortality in patients with ICH. This study aimed to compare pathogenetic subtypes between the first and recurrent ICH.

Methods—

This study obtained data related to 4578 consecutive acute patients with ICH from the National Taiwan University Hospital Stroke Registry during January 1995 to December 2013. Using the SMASH-U method, patients were classified into 6 subtypes. We then analyzed the outcomes of first-ever ICH cases and pathogenetic classification of recurrent ICH.

Results—

Among 3785 patients who experienced first-ever ICH (male, 63.3%; mean age, 58.7±17.0 years), the most common cause was hypertensive angiopathy (54.9%), followed by CAA (12.2%), systemic disease (12.1%), undetermined (10.1%), structural vascular lesions (7.8%), and medication related (2.9%). In 185 cases of recurrent ICH, pathogenetic differences between the 2 ICH events were observed in 34 (18.4%) cases, most of which were CAA to hypertensive angiopathy (n=10) or vice versa (n=7). The rates of ICH recurrence were highest for systemic disease-related and CAA-related ICH at 1, 5, 10, and 15 years after the indexed ICH event.

Conclusions—

In approximately one fifth of the recurrent patients with ICH, pathogenetic differences were observed between initial and recurrent events, particularly among those with CAA. It is possible that some patients with ICH with concomitant hypertensive angiopathy and CAA may have been categorized as CAA by the SMASH-U method.
Fibrinolysis for Intraventricular Hemorrhage
Authors: Khan Nickalus R. , Tsivgoulis Georgios , Lee Siang Liao , Jones G. Morgan , Green Cain S. , Katsanos Aristeidis H. , Klimo Paul , Arthur Adam S. , Elijovich Lucas , Alexandrov Andrei V.
Published: July 2014

Background and Purpose—

Intraventricular hemorrhage is associated with high mortality and poor functional outcome. The use of intraventricular fibrinolytic (IVF) therapy as an intervention in intraventricular hemorrhage is an evolving therapy with conflicting reports in the literature. The goal of this study is to investigate the impact of IVF on mortality, functional outcome, ventriculitis, shunt dependence, and rehemorrhage.

Methods—

During March and April 2014, a systematic literature search was performed identifying 1359 articles. Of these, 24 met inclusion criteria. A random effects meta-analysis was performed using both pooled and subset analysis based on study type.

Results—

Our meta-analysis demonstrated that IVF reduced mortality in intraventricular hemorrhage by nearly half (relative risk [RR], 0.55; 95% confidence interval [CI], 0.42–0.71;
P
<0.00001), increased the likelihood of good functional outcome by 66% (RR, 1.66; 95% CI, 1.27–2.19;
P
=0.0003), and also decreased the rate of shunt dependence (RR, 0.62; 95% CI, 0.42–0.93;
P
=0.02). IVF was not found to be associated with increased rates of ventriculitis (RR=1.46; 95% CI, 0.77–2.76;
P
=0.25) or rehemorrhage (RR=1.06; 95% CI, 0.66–1.70;
P
=0.80). We detected no evidence of publication bias.

Conclusions—

Our meta-analysis showed that IVF is safe and could be an effective strategy for the treatment of intraventricular hemorrhage. It may reduce mortality, improve functional outcome, and diminish the need for permanent ventricular shunting, while not increasing the risk of ventriculitis or rehemorrhage.
P-Wave Morphology and the Risk of Incident Ischemic Stroke in the Multi-Ethnic Study of Atherosclerosis
Authors: Kamel Hooman , Soliman Elsayed Z. , Heckbert Susan R. , Kronmal Richard A. , Longstreth W.T. , Nazarian Saman , Okin Peter M.
Published: July 2014

Background and Purpose—

Emerging data suggest that left atrial disease may cause ischemic stroke in the absence of atrial fibrillation or flutter (AF). If true, this condition may provide a cause for many strokes currently classified as cryptogenic.

Methods—

Among 6741 participants in the Multi-Ethnic Study of Atherosclerosis who were free of clinically apparent cerebrovascular or cardiovascular disease (including AF) at baseline, we examined the association between markers of left atrial abnormality on a standard 12-lead ECG—specifically P-wave area, duration, and terminal force in lead V
1
—and the subsequent risk of ischemic stroke while accounting for incident AF.

Results—

During a median follow-up of 8.5 years, 121 participants (1.8%) had a stroke and 541 participants (8.0%) were diagnosed with AF. In Cox proportional hazards models adjusting for potential baseline confounders, P-wave terminal force in lead V
1
was more strongly associated with incident stroke (hazard ratio per 1 SD increase, 1.21; 95% confidence interval, 1.02–1.44) than with incident AF (hazard ratio per 1 SD, 1.11; 95% confidence interval, 1.03–1.21). The association between P-wave terminal force in lead V
1
and stroke was robust in numerous sensitivity analyses accounting for AF, including analyses that excluded those with any incident AF or modeled any incident AF as having been present from baseline.

Conclusions—

We found an association between baseline P-wave morphology and incident stroke even after accounting for AF. This association may reflect an atrial cardiopathy that leads to stroke in the absence of AF.
Immatures of Palaearctic species of the weevil genus Tychius (Coleoptera, Curculionidae): new descriptions and new bionomic data with an evaluation of their value in a phylogenetic reconstruction of the genus
Authors: SKUHROVEC JIŘÍ , GOSIK RAFAŁ , CALDARA ROBERTO
Published: July 2014

Larvae of 14 species and pupae of 12 species of Palaearctic Tychius Germar, 1817 are described for the first time. Larvae and pupae of T.meliloti Stephens, 1831, T. squamulatus Gyllenhal, 1835 and T. quinquepunctatus (Linnaeus, 1758), are redescribed with addition of new characters. They belong to 10 of 22 groups of species assembled through adult morphological characters in this region and, like all other Tychius with known biology, the studied species live on Leguminosae Papilionoideae, belonging to the tribes Genisteae, Loteae, Galegeae, Trifolieae and Vicieae. Generally larvae, but not pupae, show a few characters useful to support some groupings previously postulated on adult morphology, and also suggest some phylogenetic relationships among groups although these are partly weak because of several clear parallelisms or convergences. One of the most numerous and better known group of species, the T. stephensi group living on Trifolieae, is supported by two distinctive larval character states, whereas all the other groups seem to be distinguishable from each other at least by a unique larval character state. New bionomic data concerning larval and pupal development and adult emergence are reported for all the described species. These data confirm that this genus is highly homogeneous in habits and times of development, with unique adaptive differences in adult emergence and overwintering according to the single or double seasonal flowering of the host plant. On the basis of morphological characters of immatures and adults, a possible concordance between the evolution of Tychius and that of their host plants is discussed.