bluuebunny/crossref_metadata_2025 huggingface dataset:
What are the farm‐level impacts of Malawi's farm input subsidy program? A critical review
Authors: Lunduka Rodney , Ricker‐Gilbert Jacob , Fisher Monica
Published: October 2013

This article provides a critical analysis of the current frontier of research evaluating Malawi's Farm Input Subsidy Program (FISP), whose main objectives are increasing maize production, promoting household food security, and enhancing rural incomes. We focus on farm‐level studies in Malawi, identifying consistent and contrasting research results in order to draw important policy lessons and provide suggested avenues for future research. While national production estimates suggested dramatic increases in maize production and productivity during the years of the FISP, the farm‐level studies found relatively modest increases in maize production and yields over the same period. Consistent with the farm‐level results of modest maize production increases, there has been a relative increase in real maize prices and the country continued to import maize during most of the subsidy program years. Furthermore, there is evidence that better‐off households gained substantially more than poorer households when they participated in the program. Together these findings cast some doubt on the FISP's ability to reduce food insecurity and poverty. We propose a number of policy lessons and suggestions for rigorous investigation, including research that directly measures the causal impacts of the FISP program on poverty in Malawi.
Atopic dermatitis and the atopic march revisited
Authors: Dharmage S. C. , Lowe A. J. , Matheson M. C. , Burgess J. A. , Allen K. J. , Abramson M. J.
Published: October 2013

Atopic dermatitis (AD) has become a significant public health problem because of increasing prevalence, together with increasing evidence that it may progress to other allergic phenotypes. While it is now acknowledged that AD commonly precedes other allergic diseases, a link termed ‘the atopic march’, debate continues as to whether this represents a causal relationship. An alternative hypothesis is that this association may be related to confounding by familial factors or phenotypes that comanifest, such as early‐life wheeze and sensitization. However, there is increasing evidence from longitudinal studies suggesting that the association between AD and other allergies is independent of confounding by comanifest allergic phenotypes. The hypotheses on plausible biological mechanisms for the atopic march focus on defective skin barrier function and overexpression of inflammatory mediators released by the skin affected by AD (including thymic stromal lymphopoietin). Both human and animal studies have provided evidence supporting these potential biological mechanisms. Evidence from prevention trials is now critical to establishing a causal nature of the atopic march. An emerging area of research is investigation into environmental modifiers of the atopic march. Such information will assist in identifying secondary prevention strategies to arrest the atopic march. Despite much research into the aetiology of allergies, little progress has been made in identifying effective strategies to reduce the burden of allergic conditions. In this context, the atopic march remains a promising area of investigation.
Weighted Wilcoxon Estimators in Nonlinear Regression
Authors: Abebe Asheber , McKean Joseph W.
Published: October 2013

In this paper, we consider the estimation of parameters of a general near regression model. An estimator that minimises the weighted Wilcoxon dispersion function is considered and its asymptotic properties established under mild regularity conditions similar to those used in least squares and least absolute deviations estimation. As in linear models, the procedure provides estimators that are robust and highly efficient. The estimates depend on the choice of a weight function and diagnostics which differentiate between nonlinear fits are provided along with appropriate benchmarks. The behavior of these estimates is discussed on a real data set. A simulation study verifies the robustness, efficiency and validity of these estimates over several error distributions including the normal and a family of contaminated normal distributions.
Adding Pulsatile Vascular Stimulation to Venous Systemic Oxygen Persufflation of Liver Grafts
Authors: Lüer Bastian , Fox Mario , Efferz Patrik , Minor Thomas
Published: October 2013

The effect of adding pulsatility to gaseous oxygen persufflation during liver preservation was studied in an isolated rat liver model. Livers from male Wistar rats were retrieved 30 min after cardiac arrest of the donor and subjected to 18 h of cold storage. Some grafts were subjected to nonpulsatile or pulsatile gaseous oxygen persufflation. Graft viability was assessed thereafter upon warm reperfusion in vitro (n = 5 per group). Pulsatile persufflation significantly improved parenchymal integrity (enzyme release, bile flow) upon reperfusion, with respect to nonpulsatile persufflation or cold storage (CS) (e.g., max. release of alanine aminotransferase: 44 ± 10 vs. 178 ± 29 vs. 345 ± 100 U/L; pulsatile vs. nonpulsatile persufflation vs. CS).The effect was associated with the prevention of the ischemic decline in gene and protein expression of the vasoprotective Krüppel‐like factor 2, increased perfusate levels of the endogenous vasodilator nitric oxide, and reduced portal vascular resistance upon reperfusion, while nonpulsatile persufflation was less effective (e.g., vascular resistance: 1235 ± 108 vs. 1607 ± 155 vs. 2215 ± 208 Pa s/mL; pulsatile vs. nonpulsatile persufflation vs. CS). In conclusion, pulsatile mechanostimulation of the hepatovasculature seems a genuine protective mechanism, affecting early graft recovery upon reperfusion.
Noninvasive Perioperative Evaluation of Right Ventricular Function in Children With Tetralogy of Fallot
Authors: Ye Jing‐Jing , Shu Qiang , Liu Xi‐Wang , Gu Wei‐zhong , Yu Jin , Jiang Guo‐ping
Published: October 2013

Early and accurate noninvasive means of identifying right ventricular (RV) dysfunction in children with tetralogy of Fallot (TOF) are needed. RV function was examined using tissue Doppler imaging (TDI), strain rate (SR), and strain analysis (SA) in children before (N = 37) and after (6–12 months; N = 32) TOF repair, and in a control group of children (N = 37). Plasma concentrations of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and matrix metalloproteinase 9 (MMP‐9) were measured. TDI, SR, and SA revealed that RV systolic and diastolic function indices were lower preoperatively in the TOF group compared with the control group, and did not improve after TOF repair. Plasma NT‐proBNP concentrations were significantly higher in the TOF group pre‐ and postoperatively compared with the control group. In the preoperative TOF group, NT‐proBNP concentration was significantly correlated with peak systolic SR and systolic strain in the mid segments of RV free wall. Plasma MMP‐9 concentrations were significantly increased in the preoperative TOF group compared with the control group, and significantly correlated with plasma NT‐proBNP and logNT‐proBNP concentrations. RV function correlated with plasma NT‐proBNP concentrations in children with TOF. Assessment of this noninvasive measure may help identify RV dysfunction in patients with TOF before they become clinically symptomatic.
Extracorporeal Life Support After Cardiac Surgery in Children: Outcomes From a Single Institution
Authors: Sasaki Takashi , Asou Toshihide , Takeda Yuko , Onakatomi Yasuko , Tominaga Takashi , Yamamoto Yusuke
Published: October 2013

Extracorporeal life support (ECLS) is used after congenital heart surgery for several indications, including failure to separate from cardiopulmonary bypass, postoperative low cardiac output syndrome, and extracorporeal cardiopulmonary resuscitation. Here, we assessed the outcomes of ECLS in children after cardiac surgery at our institution. Medical records of all children who required postoperative ECLS at our institution were reviewed. Between 2003 and 2011, 36 (1.4%) of 2541 pediatric cardiac surgical cases required postoperative ECLS. Median age of patients was 64 days (range: 0 days–4.1 years). ECLS was in the form of either extracorporeal membrane oxygenation (ECMO; n = 24) or ventricular assist system (VAS; n = 12). Mean duration of ECLS was 4.9 ± 4.2 days. Overall, 21 patients (58%) were weaned off ECLS, and 17 patients (47%) were successfully discharged from the hospital. Patients with biventricular heart (BVH) had higher survival‐to‐hospital discharge rates compared with those with univentricular heart (UVH) (P = 0.019). Regarding ECLS type, UVH patients who received VAS showed higher rates of device discontinuation than UVH patients who received ECMO (P = 0.012). However, rates of hospital discharge were not significantly different between UVH patients who received VAS or ECMO. Surgical interventions, such as banding of Blalock–Taussig shunt to reduce pulmonary blood flow or placing bidirectional cavopulmonary shunt to minimize ventricular volume overload, were effective for weaning off ECLS in patients with UVH. ECLS is beneficial to children with low cardiac output after cardiac surgery. Rates of survival‐to‐hospital discharge were higher in BVH patients than UVH patients. Additional interventions to reduce ventricular volume load may be effective for discontinuing ECLS in patients with UVH.
Testing for the Multivariate Stochastic Order Among Ordered Experimental Groups with Application to Dose–Response Studies
Authors: Davidov Ori , Peddada Shyamal
Published: October 2013

The comparison of two or more ordered experimental groups based on multivariate data is common in a variety of applications such as toxicology, clinical trials and drug development, to name just a few. In this article, we develop a nonparametric methodology for analyzing such data. In particular we propose a global K sample nonparametric test for order among vector valued outcomes. The testing procedure can also be used in a post-hoc fashion to answer questions about the ordering of subgroups and/or single outcomes within any subset of experimental groups. Such a methodology does not currently exist. In contrast with standard methodology such as multivariate analysis of variance (MANOVA), and its nonparametric analogues, we do not assume that the groups differ only by a location parameter or that the components of the response vector have the same marginal distributions between and across groups, that is, we allow for the shape of the distribution to change across groups. We emphasize that our test compares the outcome distributions, not just their mean tendencies, and explicitly incorporates and exploits the order constraints. Consequently it is more powerful than the existing unordered tests. The methodology is illustrated using genotoxicity data where the effect of hydrogen peroxide exposure on damage to DNA is evaluated using a comet assay.
Synonymous nucleotide polymorphisms influence Dombrock blood group protein expression in K562 cells
Authors: de Coulgeans Cécile Durousseau , Silvy Monique , Halverson Gregory , Chiaroni Jacques , Bailly Pascal , Chapel‐Fernandes Sylvie
Published: October 2013

To gain further insight into ART4 (DO) gene alleles (DO*A, DO*JO1, DO*A‐WL, DO*DOYA, DO*B, DO*B‐WL, DO*B‐SH‐Q149K, DO*B‐(WL)‐I175N, DO*HY1, DO*HY2, DO*DOMR) and evaluate the impact of synonymous nucleotide polymorphisms on protein expression and mRNA accumulation of DO*A‐HA, DO*A‐SH and DO*B‐SH alleles, human erythroleukaemic K562 cells were transducted with variant DO‐lentiviral particles and analysed by flow cytometry and quantitative reverse transcription polymerase chain reaction. Monoclonal antibody (MoAb) detection of DO*A‐HA and DO*JO1 transductants was lower than DO*A transductants, while detection of DO*A‐SH, DO*A‐WL and DO*DOYA transductants was higher. Variant DO*B alleles, i.e. DO*B‐SH, DO*B‐WL, DO*HY1, DO*HY2 and DO*DOMR, showed reduced MoAb binding. The unexpected modifications of protein expression of the DO*A‐HA, DO*A‐SH and DO*B‐SH alleles that differ from the DO*A or DO*B alleles by a single synonymous polymorphism were abolished by reversion, thus implying involvement of these polymorphisms. Depending on the Leu208 codon used, detection level ranged from 1 to 4·14. In the variant alleles resulting from single synonymous polymorphism, mRNA accumulation correlated roughly with MoAbs detection levels, suggesting post‐transcriptional regulation. Other than a few reports involving aberrant splicing, the experiments described herein provide the first evidence that synonymous nucleotide polymorphisms can influence Dombrock blood group expression. Such polymorphisms should be taken into account for molecular screening and potential impact on transfusion.
Disability and Perceptions of Work and Management
Authors: Jones Melanie K.
Published: October 2013

Matched employee–employer data from the 2004 Workplace Employment Relations Survey are used to examine differences in work‐related perceptions between disabled and non‐disabled employees. Even after accounting for differences in personal, job and workplace characteristics, disabled employees are found to hold more negative views on the treatment of workers by managers and, consistent with this, they express less job satisfaction and commitment towards their organization. The influence of disability is also examined across workplaces defined by sector, the presence of disability‐related policies and practices, and employee views of management to explore the role of corporate culture.
Extent of lymph node dissection at nephrectomy affects cancer‐specific survival and metastatic progression in specific sub‐categories of patients with renal cell carcinoma (RCC)
Authors: Capitanio Umberto , Suardi Nazareno , Matloob Rayan , Roscigno Marco , Abdollah Firas , Di Trapani Ettore , Moschini Marco , Gallina Andrea , Salonia Andrea , Briganti Alberto , Montorsi Francesco , Bertini Roberto
Published: October 2013

Objective

To test whether the number of lymph nodes removed affects cancer‐specific survival (CSS) or metastatic progression‐free survival (MPFS) in different renal cell carcinoma (RCC) scenarios.

Methods

We used Cox regression analyses to analyse the effect of the number of lymph nodes removed on CSS and MPFS in 1983 patients with RCC treated with nephrectomy.

To adjust for possible clinical and surgical selection bias, analyses were further adjusted for number of positive nodes, presence of metastases, age, performance status, T stage, tumour size and grade.

Results

The prevalence of lymph node invasion was 6.1%. The mean follow‐up period was 83.3 months.

Multivariable analyses showed that the number of nodes removed had an independent, protective effect on CSS in patients with pT2a–pT2b or pT3c–pT4 RCC (hazard ratio [HR] 0.91, P = 0.008 and HR 0.89, P < 0.001, respectively), in patients with bulky tumours (tumour size >10 cm, HR 0.97, P = 0.03) or when sarcomatoid features were found (HR 0.81, P = 0.006).

The removal of each additional lymph node was associated with a 3–19% increase in CSS.

When considering MPFS as an endpoint, the number of nodes removed had an independent, protective effect in the same patient categories.

Conclusions

When clinically indicated, the number of nodes removed affects CSS and MPFS in specific sub‐categories of patients with RCC.
Biology of AQP4 and Anti‐AQP4 Antibody: Therapeutic Implications for NMO
Authors: Verkman A. S. , Phuan Puay‐Wah , Asavapanumas Nithi , Tradtrantip Lukmanee
Published: October 2013

The water channel aquaporin‐4 (AQP4) is the target of the immunoglobulin G autoantibody (AQP4‐IgG) in neuromyelitis optica (NMO). AQP4 is expressed in foot processes of astrocytes throughout the central nervous system, as well as in skeletal muscle and epithelial cells in kidney, lung and gastrointestinal organs. Phenotype analysis of AQP4 knockout mice indicates the involvement of AQP4 in water movement into and out of the brain, astrocyte migration, glial scar formation and neuroexcitatory phenomena. AQP4 monomers form tetramers in membranes, which further aggregate to form supramolecular assemblies called orthogonal arrays of particles. AQP4‐IgG is pathogenic in NMO by a mechanism involving complement‐ and cell‐mediated astrocyte cytotoxicity, which produces an inflammatory response with oligodendrocyte injury and demyelination. AQP4 orthogonal arrays are crucial in NMO pathogenesis, as they increase AQP4‐IgG binding to AQP4 and greatly enhance complement‐dependent cytotoxicity. Novel NMO therapeutics are under development that target AQP4‐IgG or AQP4, including aquaporumab monoclonal antibodies and small molecules that block AQP4‐IgG binding to AQP4, and enzymatic inactivation strategies to neutralize AQP4‐IgG pathogenicity.
Clinical Spectrum and Treatment of Neuromyelitis Optica Spectrum Disorders: Evolution and Current Status
Authors: Sato Douglas Kazutoshi , Lana‐Peixoto Marco Aurelio , Fujihara Kazuo , de Seze Jerome
Published: October 2013

Neuromyelitis optica (NMO) is an inflammatory neurologic disease clinically characterized by severe optic neuritis (ON) and transverse myelitis (TM). The relationship between NMO and multiple sclerosis (MS) has long been a matter of debate. However, the discovery of an NMO‐specific autoantibody, NMO‐immunoglobulin G/aquaporin 4 (AQP4) antibody, has dramatically advanced our understanding of the disease, and the clinical, magnetic resonance imaging (MRI), optical coherence tomography, and laboratory examinations have clarified unique features of NMO that are distinct from MS. The term NMO spectrum disorders (NMOSD) incorporating spatially limited forms was introduced, as patients with recurrent or simultaneous bilateral ON or recurrent longitudinally extensive TM (LETM) alone are also often AQP4 antibody‐seropositive. Moreover, studies of seropositive cases have shown that more than half of them have brain lesions, some of which are unique to NMO, and can be the onset manifestation. Some clinical features of AQP4 antibody‐seronegative NMO differ from seropositive, but it remains unknown whether they are pathologically distinct. Immunosuppressive treatments are effective for acute attacks and prevention of relapses of NMOSD, and new molecularly targeted drugs are under investigation. Importantly, some disease modifying drugs for MS may exacerbate NMOSD, making early differential diagnosis of the two diseases crucial. We review the evolving clinical spectrum, the updated clinical, MRI, neuro‐ophthalmological and laboratory findings, and the current status of treatment in NMOSD.
Structure–activity relationships of the N‐terminus of calcitonin gene‐related peptide: key roles of alanine‐5 and threonine‐6 in receptor activation
Authors: Hay Debbie L , Harris Paul W R , Kowalczyk Renata , Brimble Margaret A , Rathbone Dan L , Barwell James , Conner Alex C , Poyner David R
Published: October 2013

Background and Purpose

The N‐terminus of calcitonin gene‐related peptide (CGRP) is important for receptor activation, especially the disulphide‐bonded ring (residues 1–7). However, the roles of individual amino acids within this region have not been examined and so the molecular determinants of agonism are unknown. This study has examined the role of residues 1, 3–6 and 8–9, excluding Cys‐2 and Cys‐7.

Experimental Approach

CGRP derivatives were substituted with either cysteine or alanine; further residues were introduced at position 6. Their affinity was measured by radioligand binding and their efficacy by measuring cAMP production in SK‐N‐MC cells and β‐arrestin 2 translocation in CHO‐K1 cells at the CGRP receptor.

Key Results

Substitution of Ala‐5 by cysteine reduced affinity 270‐fold and reduced efficacy for production of cAMP in SK‐N‐MCs. Potency at β‐arrestin translocation was reduced by ninefold. Substitution of Thr‐6 by cysteine destroyed all measurable efficacy of both cAMP and β‐arrestin responses; substitution with either alanine or serine impaired potency. Substitutions at positions 1, 4, 8 and 9 resulted in approximately 10‐fold reductions in potency at both responses. Similar observations were made at a second CGRP‐activated receptor, the AMY1(a) receptor.

Conclusions and Implications

Ala‐5 and Thr‐6 are key determinants of agonist activity for CGRP. Ala‐5 is also very important for receptor binding. Residues outside of the 1–7 ring also contribute to agonist activity.
The opioid methadone induces a local anaesthetic‐like inhibition of the cardiacNa+channel,Nav1.5
Authors: Schulze V , Stoetzer C , O'Reilly A O , Eberhardt E , Foadi N , Ahrens J , Wegner F , Lampert A , de la Roche J , Leffler A
Published: October 2013

Background and Purpose

Treatment with methadone is associated with severe cardiac arrhythmias, a side effect that seems to result from an inhibition of cardiachERG K+channels. However, several other opioids are inhibitors of voltage‐gatedNa+channels. Considering the common assumption that an inhibition of the cardiacNa+channelNav1.5, is the primary mechanism for local anaesthetic (LA)‐induced cardiotoxicity, we hypothesized that methadone hasLA‐likeproperties leading to a modulation ofNav1.5 channels.

Experimental Approach

The whole‐cell patch clamp technique was applied to investigate the effects of methadone on wild‐type and mutant humanNav1.5 channels expressed inHEK293 cells. A homology model of human Nav1.5 channels was used to perform automated ligand‐docking studies.

Key Results

Methadone inhibitedNav1.5 channels in a state‐dependent manner, that is, tonic block was stronger with inactivated channels than with resting channels and a use‐dependent block at 10 Hz. Methadone induced a concentration‐dependent shift of the voltage dependency of both fast and slow inactivation towards more hyperpolarized potentials, and impaired recovery from fast and slow inactivation. TheLA‐insensitive mutantsN406KandF1760Aexhibited reduced tonic and use‐dependent block by methadone, and docking predictions positioned methadone in a cavity that was delimited by the residueF1760. Dextromethadone and levomethadone induced discrete stereo‐selective effects onNav1.5 channels.

Conclusions and Implications

Methadone interacted with theLA‐binding site to inhibitNav1.5 channels. Our data suggest that these channels are a hitherto unrecognized molecular component contributing to cardiac arrhythmias induced by methadone.
Role of CXCR2 and TRPV1 in functional, inflammatory and behavioural changes in the rat model of cyclophosphamide‐induced haemorrhagic cystitis
Authors: Dornelles Fabiana N , Andrade Edinéia L , Campos Maria M , Calixto João B
Published: October 2013

Background and Purpose

Cyclophosphamide induces urotoxicity characterized by the development of cystitis, which involves bladder overactivity and inflammation. Here, we investigated the roles of chemokine receptor 2 (CXCR2) and transient receptor potential vanilloid 1 (TRPV1) channels in a rat model of cyclophosphamide‐induced cystitis.

Experimental Approach

Cystitis induced by cyclophosphamide in rats was assessed by gross morphology, histology and immunohistochemistry of bladder tissue. mRNA for CXCR2 and TRPV1 channels were measured by RT‐PCR. Nociceptive responses in paw and abdomen, along with cystometric measures were recorded.

Key Results

Cyclophosphamide, i.p., induced pain behaviour, bladder inflammation and voiding dysfunction. The CXCR2 antagonist, SB225002, the TRPV1 channel antagonist, SB366791 or their combination reduced the mechanical hypersensitivity of paw and abdominal area and nociceptive behaviour after cyclophosphamide. Cyclophosphamide‐induced cystitis was characterized by haemorrhage, oedema, neutrophil infiltration and other inflammatory changes, which were markedly decreased by the antagonists. Up‐regulation of CXCR2 and TRPV1 mRNA in the bladder after cyclophosphamide was inhibited by SB225002, SB366791 or their combination. Expression of CXCR2 and TRPV1 channels was increased in the urothelium after cyclophosphamide. Bladder dysfunction was shown by increased number of non‐voiding contractions (NVCs) and bladder pressures and a reduction in bladder capacity (BC), voided volume (VV) and voiding efficiency (VE). SB225002 or its combination with SB366791 reduced bladder pressures, whereas SB225002, SB366791 or their combination increased BC, VV and VE, and also reduced the number of NVCs.

Conclusions and Implications

CXCR2 and TRPV1 channels play important roles in cyclophosphamide‐induced cystitis in rats and could provide potential therapeutic targets for cystitis.
Histone acetyltransferase Hbo1 destabilizes estrogen receptor α by ubiquitination and modulates proliferation of breast cancers
Authors: Iizuka Masayoshi , Susa Takao , Takahashi Yoshihisa , Tamamori‐Adachi Mimi , Kajitani Takashi , Okinaga Hiroko , Fukusato Toshio , Okazaki Tomoki
Published: October 2013

The estrogen receptor (ER) is a key molecule for growth of breast cancers. It has been a successful target for treatment of breast cancers. Elucidation of the ER expression mechanism is of importance for designing therapeutics for ER‐positive breast cancers. However, the detailed mechanism of ER stability is still unclear. Here, we report that histone acetyltransferase Hbo1 promotes destabilization of estrogen receptor α (ERα) in breast cancers through lysine 48‐linked ubiquitination. The acetyltransferase activity of Hbo1 is linked to its activity for ERα ubiquitination. Depletion of Hbo1 and anti‐estrogen treatment displayed a potent growth suppression of breast cancer cell line. Hbo1 modulated transcription by ERα. Mutually exclusive expression of Hbo1 and ERα was observed in roughly half of the human breast tumors examined in the present study. Modulation of ER stability by Hbo1 in breast cancers may provide a novel therapeutic possibility.
Quantitative Sequence–Activity Model Analysis of Oligopeptides Coupling an Improved High‐Dimension Feature Selection Method with Support Vector Regression
Authors: Wang Lifeng , Dai Zhijun , Zhang Hongyan , Bai Lianyang , Yuan Zheming
Published: October 2013

Five hundred and thirty‐one physicochemical property parameters of amino acids were directly used as descriptors to characterize the structure of oligopeptides. Based on support vector regression (SVR), a novel rapid selection method called binary matrix resetting filter (BMRF) was proposed to nonlinearly select high‐dimensional features and then multiround last‐elimination (MRLE) was used for subtle screening. The reserved descriptors were used to construct the regression model with SVR, which was then applied to the quantitative sequence–activity model (QSAM) analysis for two oligopeptide systems. Compared with the widely used 16 kinds of amino acid descriptors, four QSAM modeling methods and four feature selection methods, our work shows a significant improvement in modeling performance, especially in external prediction. Furthermore, the real biochemical significance corresponding to reserved descriptors can be given directly, and the interpretability of the established QSAM model is improved significantly. This novel method has a high potential to become an available tool for regression analysis of high‐dimension data, such as QSAM modeling of peptides or even proteins.
Unsymmetrical Oxovanadium Complexes Derived from Salicylaldehyde and Phenanthroline: Synthesis, DNA Interactions, and Antitumor Activities
Authors: Liao Xiangwen , Pan Weijian , He Rongwei , Guo Haiwei , Ying Peng , Lu Jiazheng
Published: October 2013

Two unsymmetrical oxovanadium complexes incorporating salicylaldehyde derivate and phenanthroline [VO(DESAA)(phen)] (1), (DESAA = 4‐(diethylamino)salicylaldehyde anthranilic acid, phen = phenanthroline) and [VO(CLSAA)(phen)] (2), (CLSAA = 5‐chlorosalicylaldehyde anthranilic acid)] have been synthesized and characterized. The interactions of the complexes with CT‐DNA were studied using different techniques. Complexes 1 and 2 interact with CT‐DNA by intercalative modes and can efficiently cleave pBR322 DNA after light irradiation. The two complexes showed high cytotoxic activities against myeloma cell (Ag8.653) and gliomas cell (U251) lines. Interestingly, complex 1 exhibited greater antitumor efficiency, larger binding affinity with CT‐DNA, and better cleaving ability than those of complex 2. In addition, their antitumor mechanism has been analyzed by using cell cycle analysis, apoptosis, and Annexin V‐FITC/PI assay. The results showed that complex 1 can cause G2/M‐phase arrest of the cell cycle, exhibit a significantly induced apoptosis in Ag8.653 cells, and display typical morphological apoptotic characteristics. These complexes induced proliferative suppression of Ag8.653 cells via the induction of apoptosis.
Impact of subclinical haemorrhage on the pituitary gland in patients with pituitary adenomas
Authors: Kinoshita Yasuyuki , Tominaga Atsushi , Usui Satoshi , Arita Kazunori , Sugiyama Kazuhiko , Kurisu Kaoru
Published: October 2013

Objective

Advanced magnetic resonance imaging (MRI) and optical instruments for surgery frequently demonstrate subclinical haemorrhage in pituitary adenomas; however, the effects of subclinical haemorrhage on pituitary glands remain unclear. We sought to clarify the pituitary function in patients with subclinical pituitary adenoma haemorrhage (SPAH).

Design/Patients

Between January 2006 and December 2012, we retrospectively reviewed 328 consecutive patients who underwent surgery for pituitary adenoma. SPAH was defined as an intratumoral haemorrhage based on both 3 tesla MRI and operative findings, with no clinical symptoms of acute pituitary adenoma apoplexy. The pituitary dysfunction assessed using pre‐ and postoperative provocative tests was investigated in patients categorized into three groups: nonapoplectic adenoma, adenoma with SPAH and adenoma with clinical apoplexy.

Measurements

The main outcome measure was the incidence of pituitary dysfunction.

Results

The overall incidence of nonapoplectic adenomas, adenomas with SPAH and adenomas with clinical apoplexy was 82·3%, 14·3% and 3·4%, respectively. Clinical pituitary apoplexy frequently occurred in male patients with large nonfunctioning adenomas, causing pituitary dysfunction. Contrastingly, the incidence of SPAH was significantly higher in the patients with prolactinoma (P = 0·0260), including those with relatively small adenomas (P = 0·0007). No medications, such as dopamine agonists or somatostatin analogues, were observed to affect the occurrence of SPAH. No deterioration of the pituitary function was observed in the SPAH patients in comparison with the patients with nonapoplectic adenoma, and the size of the haematoma occupying the pituitary adenoma did not exhibit any relationships with the deterioration of the pituitary function. Furthermore, SPAH caused no deterioration of the pituitary function after a surgery based on the postoperative provocation tests.

Conclusions

Subclinical pituitary adenoma haemorrhage does not cause any added dysfunction in pituitary glands. Signs of haemorrhage in pituitary adenomas do not necessitate immediate tumour decompression surgery, if there are no symptoms of acute haemorrhage.
Combining Statins with Tissue Plasminogen Activator Treatment After Experimental and Human Stroke: A Safety Study on Hemorrhagic Transformation
Authors: Campos Mireia , García‐Bonilla Lidia , Hernández‐Guillamon Mar , Barceló Verónica , Morancho Anna , Quintana Manolo , Rubiera Marta , Rosell Anna , Montaner Joan
Published: October 2013

Aims

Statins may afford neuroprotection against ischemic injury, but it remains controversial whether combined treatment with tissue plasminogen activator (tPA) after stroke increases the risk of hemorrhagic transformation (HT), the major tPA‐related complication. We evaluated the safety of combining statin with tPA administration during the acute phase of both experimental and human stroke.

Methods

The occurrence and severity of HT, infarct volume, and neurological outcome were evaluated in spontaneous hypertensive rats (SHR) subjected to embolic middle cerebral arterial occlusion (MCAO), which received vehicle or simvastatin (20 mg/kg), 15 min after ischemia and tPA (9 mg/kg) 3 h after ischemia. Additionally, HT rate was evaluated in stroke patients who were treated with tPA (0.9 mg/kg) within 3 h after symptom onset, considering whether or not were under statins treatment when the stroke occurred.

Results

In the experimental study, no differences in HT rates and severity were found between treatment groups, neither regarding mortality, neurological deficit, infarct volume, or metalloproteinases (MMPs) brain content. In the clinical study, HT rates and hemorrhage type were similar in stroke patients who were or not under statins treatment.

Conclusion

This study consistently confirms that the use of statins does not increase HT rates and severity when is combined with tPA administration.
Impact of slow transit constipation on the outcome of laparoscopic ventral rectopexy for obstructed defaecation associated with high grade internal rectal prolapse
Authors: Gosselink M. P. , Adusumilli S. , Harmston C. , Wijffels N. A. , Jones O. M. , Cunningham C. , Lindsey I.
Published: October 2013

Aim

Limited literature exists on whether slow colonic transit adversely influences the results of outlet obstruction surgery. We compared the functional results of laparoscopic ventral rectopexy (LVR) for obstructed defaecation secondary to high grade internal rectal prolapse in patients with normal and slow colonic transit.

Method

Consecutive patients suffering from obstructed defaecation associated with an internal rectal prolapse, who underwent an LVR between 2007 and 2011, were identified from a prospective database. All patients underwent preoperative defaecating proctography, anorectal manometry and colonic transit studies. Symptoms were assessed preoperatively and at 12 months after operation using a standardized questionnaire incorporating the Patient Assessment of Constipation Symptoms (PAC‐SYM) questionnaire, the Fecal Incontinence Severity Index (FISI), the Patient Assessment of Constipation Quality of Life (PAC‐QOL) scale and the Gastrointestinal Quality of Life Index (GIQLI).

Results

In all, 151 patients underwent LVR, 109 with normal and 42 with slow colonic transit. Preoperatively there was no significant difference between the two groups in age, sex, PAC‐SYM score or FISI score. The PAC‐SYM and FISI scores were significantly reduced in both groups at 12 months (P < 0.001). When comparing the change from baseline of PAC‐SYM between patients with and without slow transit constipation, a significant difference was observed (P = 0.030) with changes of 58% and 40%. Quality of life (GIQLI and PAC‐QOL) was equally improved in both groups. Quality of life improvement was less in patients with right colonic stasis.

Conclusion

Slow colonic transit has no adverse impact on function and quality of life after LVR for obstructed defaecation due to high grade internal rectal prolapse.
Integrating Cognitive Process and Descriptive Models of Attitudes and Preferences
Authors: Hawkins Guy E. , Marley A.A.J. , Heathcote Andrew , Flynn Terry N. , Louviere Jordan J. , Brown Scott D.
Published: October 2013

Discrete choice experiments—selecting the best and/or worst from a set of options—are increasingly used to provide more efficient and valid measurement of attitudes or preferences than conventional methods such as Likert scales. Discrete choice data have traditionally been analyzed with random utility models that have good measurement properties but provide limited insight into cognitive processes. We extend a well‐established cognitive model, which has successfully explained both choices and response times for simple decision tasks, to complex, multi‐attribute discrete choice data. The fits, and parameters, of the extended model for two sets of choice data (involving patient preferences for dermatology appointments, and consumer attitudes toward mobile phones) agree with those of standard choice models. The extended model also accounts for choice and response time data in a perceptual judgment task designed in a manner analogous to best–worst discrete choice experiments. We conclude that several research fields might benefit from discrete choice experiments, and that the particular accumulator‐based models of decision making used in response time research can also provide process‐level instantiations for random utility models.
Immunosuppression after renal allograft failure: a survey of US practices
Authors: Bayliss George P. , Gohh Reginald Y. , Morrissey Paul E. , Rodrigue James R. , Mandelbrot Didier A.
Published: October 2013

Background

Little data exist to guide the management of immunosuppression after renal graft failure. More aggressive tapering of immunosuppressive medications may reduce the risk of infection, but may increase the risk of rejection and sensitization.

Methods

To document current practices in the US, we emailed a questionnaire to medical and surgical transplant directors as identified by the United Network for Organ Sharing (UNOS).

Results

Emails were sent to 221 programs, of which 93 (42.1%) responded. About 24.7% of respondents reported adjusting immunosuppression according to a standard protocol; 75.3% said practices are physician dependent. The majority said that 80 or 100% of patients are off all immunosuppression one yr after returning to dialysis. The most important factors cited in deciding whether to stop immunosuppression were plans to retransplant (40.2%) and signs and symptoms of rejection (37.0%). When asked which immunosuppressive medications are continued indefinitely, 21.5% responded prednisone and 71.0% said none. Respondents most commonly said they performed graft nephrectomy only if there are signs and symptoms of rejection (47.3%) or if signs and symptoms of rejection fail to respond to steroids (34.4%).

Conclusions

In the absence of good data to guide decisions on immunosuppression in patients with failed allografts, practices in the US vary greatly. More data are needed to determine which policies lead to the best outcomes.
Allotransplanting donor kidneys after resection of a small renal cancer or contralateral healthy kidneys from cadaveric donors with unilateral renal cancer: a systematic review
Authors: Yu Nengwang , Fu Shuai , Fu Zhihou , Meng Jianzhong , Xu Zhonghua , Wang Baocheng , Zhang Aimin
Published: October 2013

This systematic review summarizes evidence on allotransplantation of donor kidneys after resection of a small renal cancer or contralateral healthy kidneys from cadaveric donors with unilateral renal cancer. Eligible studies were identified by screening four bibliographic databases, contacting key authors, and analyzing the bibliographies of included studies. Two reviewers independently assessed the reports for inclusion and extracted data, which were summarized as a narrative review. In the 20 case report or case series studies included in the analysis, there were 97 documented cases of donor kidney transplantation after resection of small renal cancer without pathologically confirmed recurrence, whereas 22 cases used contralateral healthy kidneys from cadaveric donors with unilateral renal cancer with one case of cancer recurrence. These results suggest that the use of donor kidneys after resection of small renal cancer is associated with a relatively low cancer recurrence rate.
Production of anti‐ABO blood group antibodies after minor ABO‐incompatible bone marrow transplantation in NOD/SCID/gamma(c)(null) mice
Authors: Tomita Hirofumi , Fuchimoto Yasushi , Mori Takehiko , Kato Jun , Uemura Tomoe , Handa Makoto , Tazawa Hirofumi , Ohdan Hideki , Okamoto Shinichiro , Kuroda Tatsuo
Published: October 2013

ABO incompatibility is a barrier for solid organ transplantation, but not for hematopoietic stem cell transplantation. To investigate tolerance induction, we enrolled patients who had undergone minor ABO‐incompatible (O into A group, n = 6) and ABO‐identical (O into O group, n = 4) bone marrow transplantation (BMT). None of the six O into A patients were positive for recipient‐specific (anti‐blood group A) isohemagglutinins, whereas all four O into O patients were. Peripheral blood mononuclear cells (PBMCs) were engrafted into NOD/SCID/gamma(c)(null) (NOG) mice, followed by sensitization of blood group A red blood cells. Anti‐blood group A antibodies (Abs) in the sera of the patients and the human PBMC‐engrafted NOG mice were measured by enzyme‐linked immunosorbent assays. Anti‐blood group A Abs in the patients' sera were significantly correlated with anti‐A isohemagglutinin titers (p < 0.01). In the human PBMC‐engrafted NOG mice, anti‐blood group A Abs were significantly lower in the O into A group than in the O into O group (p < 0.05), despite ex vivo restimulation of B cells. The results of this study suggest that long after receiving minor ABO‐incompatible BMT, B cells derived from newly engrafted donor precursor cells were induced tolerance to recipient‐specific antigens.
Cytodiagnosis of endometrial carcinoma and hyperplasia on imprint smears with additional immunocytochemistry using Ki‐67 and p53 biomarkers
Authors: Apostolou G. , Apostolou N. , Nikolaidou C. , Kavantzas N. , Patsouris E. , Athanassiadou P.
Published: October 2013

Objective

It is said to be difficult to interpret the different endometrial lesions by cytomorphology; however, evaluation of the microarchitecture of the cell clumps and application of immunocytochemistry can improve diagnostic accuracy. The aim of the present study was to evaluate cytolomorphological features and correlate them with the histological diagnosis of benign and malignant endometrial lesions, and to investigate certain immunocytochemical biomarkers to achieve a more accurate cytodiagnosis.

Methods

In the present study, we graded the cytomorphology on imprint smears of 35 low‐grade endometrial endometrioid carcinomas compared with 23 cases of endometrium ranging from disordered proliferative to benign hyperplastic. Additionally, 10 cases of high‐grade endometrial carcinoma and 11 cases of atrophic endometrium were evaluated. Ki‐67 and p53 biomarkers were applied to the cytological smears.

Results

A total cytological score less than six, resulting from nuclear overlapping, nuclear/cytoplasmic ratio, the presence of a branched pattern, vesicular cytoplasm and loss of cohesiveness, distinguished all the cases of disordered proliferative and benign hyperplastic endometrium from low‐grade endometrioid carcinomas of endometrium (P < 0.0001). The application of different cut‐off values for Ki‐67 and p53 helped differentiate certain endometrial lesions in our study. The integration of the immunocytochemical score of Ki‐67 and p53 into the cytological score resulted in a final score that was also diagnostically useful.

Conclusions

The results of the present study demonstrated that evaluation of certain cytological features along with specific immunocytochemical findings could improve the accuracy of endometrial cytodiagnosis but our findings need to be tested in a routine clinical situation, using pre‐operative cytological samples, to ascertain whether the diagnostic criteria are reproducible.
A 36‐week retrospective open trial comparing the efficacy of biological therapies in nail psoriasis
Authors: Bardazzi Federico , Antonucci Valentina A. , Tengattini Vera , Odorici Giulia , Balestri Riccardo , Patrizi Annalisa
Published: October 2013

Background

Nail psoriasis occurs in about 50% of psoriatic patients and can be psychologically devastating since it appears on visible areas. Up to now there is no evidence about what biological drugs is the most effective on nail psoriasis.

Objectives

The aim of our study was to determine if one of the four biological drugs approved in our country (infliximab, adalimumab, etanercept, ustekinumab) is more effective than the others for nail psoriasis.

Materials and methods

A single‐center, retrospective study was conducted to assess the efficacy of biological therapies in patients with moderate to severe psoriasis with nail involvement. NAPSI was evaluated in all psoriatic patients. Kruskal‐Wallis and Fisher's exact tests were used to analyze the data.

Results

A global statistically significant improvement in mean NAPSI from baseline to 12, 24 and 36 weeks was observed in all patients. At 12 weeks 27.78% of the patients reach NAPSI 75, at 24 weeks 81.48% and at 36 weeks 88.89%. The improvement in nail psoriasis is not significantly different between groups. An improvement in the mean Psoriasis Area and Severity Index score was also achieved

Conclusions

Biological therapies have shown to ameliorate psoriatic nail lesions. We did not find any statistically significant differences between the four biological drugs investigated.
Nonsyndromic types of ichthyoses – an update
Authors: Traupe Heiko , Fischer Judith , Oji Vinzenz
Published: October 2013

Ichthyoses are genetically determined Mendelian disorders of cornification (MEDOC) that are characterized by universal scaling. Today we distinguish between non‐syndromic and syndromic forms. Ichthyosis vulgaris is the most frequent type (prevalence 1:100) and is caused by autosomal semi‐dominant filaggrin mutations. It is associated with a higher risk for the development of atopic diseases, such as atopic eczema and allergic rhinitis. Recessive X‐linked ichthyosis (RXLI) occurs almost exclusively in boys; in Germany it has a prevalence of around 1:4,000. It is caused by steroid sulfatase deficiency and is often associated with further clinical problems, such as cryptorchidism (∼20%) or social communication deficits, such as attention deficit hyperactivity syndrome (40%) or autism (25%). Autosomal recessive congenital ichthyosis (ARCI) is genetically very heterogeneous and 8 different genes have been identified so far. The most frequent cause of ARCI is a transglutaminase 1 deficiency (prevalence 1:200, 000). Mutations in keratin genes are the cause of the keratinopathic ichthyoses, such as epidermolytic ichthyosis. They manifest at birth and often feature episodes of blistering. Most of these types are inherited as autosomal dominant traits, but autosomal recessive forms have also been described on occasion.
The Competitive Impact of Targeted Television Advertisements Using DVR Technology
Authors: Ghosh Bikram P. , Galbreth Michael R. , Shang Guangzhi
Published: October 2013

Digital video recorders (DVRs) are an emerging technology that is fundamentally changing the competitive landscape in industries that advertise on television. Perhaps the most familiar impact of DVR technology is that it enables consumers to avoid advertisements (ads) by fast forwarding through them. However, this “zipping” of ads is only one aspect of the impact of DVR technology. DVRs also collect a wealth of information at the consumer level that can be used by firms to target their ads more effectively. We examine how this targeting capability moderates the impact of ad avoidance in a competitive setting. Insights are provided on how best to manage this emerging technology in terms of the key managerial decisions of product pricing and advertising efforts, as well as its impact on profits in a competitive (duopoly) marketplace.