bluuebunny/crossref_metadata_2025 huggingface dataset:
The Synergistic Effect of Nitrogen Dopant and Calcination Temperature on the Visible-Light-Induced Photoactivity of N-Doped TiO2
Authors: Lin Yao-Tung , Weng Chih-Huang , Hsu Hui-Jan , Lin Yu-Hao , Shiesh Ching-Chang
Published: May 2013

The synergistic effect of nitrogen content and calcinations temperature on the N-doped TiO2catalysts prepared by sol-gel method was investigated. The phase and structure, chemical state, optical properties, and surface area/pore distribution of N-doped TiO2were characterized using X-ray diffraction spectrometer, high-resolution transmission electron microscope, X-ray photoelectron spectroscopy, UV-vis diffusion reflectance spectroscopy, and Brunauer-Emmett-Teller specific surface area. Finding showed that the photocatalytic activity of N-doped TiO2was greatly enhanced compared to pure TiO2under visible irradiation. N dopants could retard the transformation from anatase to rutile phase. Namely, N-doping effect is attributed to the anatase phase stabilization. The results showed nitrogen atoms were incorporated into the interstitial positions of the TiO2lattice. Ethylene was used to evaluate the photocatalytic activity of samples under visible-light illumination. The results suggested good anatase crystallization, smaller particle size, and larger surface are beneficial for photocatalytic activity of N-doped TiO2. The N-doped TiO2catalyst prepared with ammonia to titanium isopropoxide molar ratio of 2.0 and calcinated at 400°C showed the best photocatalytic ability.
Treating Type 2 Diabetes Mellitus with Traditional Chinese and Indian Medicinal Herbs
Authors: Wang Zhijun , Wang Jeffrey , Chan Patrick
Published: May 2013

Type II diabetes mellitus (T2DM) is a fast-growing epidemic affecting people globally. Furthermore, multiple complications and comorbidities are associated with T2DM. Lifestyle modifications along with pharmacotherapy and patient education are the mainstay of therapy for patients afflicted with T2DM. Western medications are frequently associated with severe adverse drug reactions and high costs of treatment. Herbal medications have long been used in the treatment and prevention of T2DM in both traditional Chinese medicine (TCM) and traditional Indian medicine (TIM). This review examinesin vivo,in vitro, and clinical evidence supporting the use of various herbs used in TCM and TIM. The problems, challenges, and opportunities for the incorporation of herbal frequently used in TCM and TIM into Western therapy are presented and discussed.
Renal Cell Carcinoma with Intraluminal Spread of the Entire Upper Urinary Tract
Authors: Kakutani Shigenori , Kume Haruki , Hirano Yoshikazu , Wakita Toshihiko , Homma Yukio
Published: May 2013

We describe an unusual case of renal cell carcinoma (RCC) involving the entire upper urinary tract. A 51-year-old female was referred to us because of macroscopic hematuria. Computed tomography revealed a renal tumor filling renal pelvis and ureter, which turned to be a clear cell RCC after nephroureterectomy.
Abdominal Cocoon Syndrome (Idiopathic Sclerosing Encapsulating Peritonitis): How Easy Is Its Diagnosis Preoperatively? A Case Report
Authors: Awe Julius A. A.
Published: May 2013

The abdominal cocoon syndrome (or idiopathic encapsulating peritonitis) is a rare cause of intestinal obstruction. It has been reported predominantly in adolescent girls living in tropical/subtropical region in which diagnosis is only made at laparotomy in most cases. The cause and pathogenesis of the condition have not been elucidated. Prolonged administration of practalol, meconium peritonitis, and tuberculous infection of the female genital tract have been incriminated as possible causes. The author reports a case of a female patient with recurrent intestinal obstruction treated for years but failed to settle down on conservative treatment during her last hospital admission and had to undergo surgery. Preoperative diagnosis of this syndrome as the cause of her intestinal obstruction was not made until at laparotomy, when a thick fibrotic peritoneal wrapping of the bowel in a concertina-like fashion with some adhesions was found. Excision of this membrane and adhesiolysis were carried out without any need for bowel resection, and this led to relief of the obstruction and patient’s complete recovery. Awareness of this benign condition in the differential diagnosis of intestinal obstruction will result in early diagnosis and correct management and prevent unnecessary bowel resections and bad outcomes.
A Qualitative Systematic Review of Older Persons’ Perceptions of Health, Ill Health, and Their Community Health Care Needs
Authors: Holm Anne Lise , Severinsson Elisabeth
Published: May 2013

The aim of this qualitative systematic review was to report a synthesis of older persons’ perceptions of health, ill health, and their community health care needs. The review questions were what characterizes older persons’ perceptions of health and ill health? and what are their community health care needs? Ten studies were identified in a systematic search for relevant qualitative papers published between January 2000 and January 2013 in the following electronic databases: PubMed, EBSCOhost/Academic Search Premier, and CINAHL. Publications were evaluated for quality, and a thematic analysis was performed. Two main themes were interpreted on a higher level: reconciliation with how life has become: and desire to regain their identity and sense of self-worth despite disability. Two themes emerged: creating meaning led to the experience of being valued in health care and society and a mental struggle to regain independence with the help of caregivers. Of special interest is the finding of perceptions related to the fear of becoming dependent on caregivers as well as the sorrow and pain caused by encountering caregivers who did not understand their desire to create meaning in their lives or their struggle for autonomy and independency.
Bayesian Estimation Applied to Stochastic Localization with Constraints due to Interfaces and Boundaries
Authors: Hoegele Wolfgang , Loeschel Rainer , Dobler Barbara , Koelbl Oliver , Zygmanski Piotr
Published: May 2013

Purpose. We present a systematic Bayesian formulation of the stochastic localization/triangulation problem close to constraining interfaces.Methods. For this purpose, the terminology of Bayesian estimation is summarized suitably for applied researchers including the presentation of Maximum Likelihood (ML), Maximum A Posteriori (MAP), and Minimum Mean Square Error (MMSE) estimation. Explicit estimators for triangulation are presented for the linear 2D parallel beam and the nonlinear 3D cone beam model. The priors in MAP and MMSE optionally incorporate (A) the hard constraints about the interface and (B) knowledge about the probability of the object with respect to the interface. All presented estimators are compared in several simulation studies for live acquisition scenarios with 10,000 samples each.Results. First, the presented application shows that MAP and MMSE perform considerably better, leading to lower Root Mean Square Errors (RMSEs) in the simulation studies compared to the ML approach by typically introducing a bias. Second, utilizing priors including (A) and (B) is very beneficial compared to just including (A). Third, typically MMSE leads to better results than MAP, by the cost of significantly higher computational effort.Conclusion. Depending on the specific application and prior knowledge, MAP and MMSE estimators strongly increase the estimation accuracy for localization close to interfaces.
The Steroid Receptor Coactivator-3 Is Required for the Development of Castration-Resistant Prostate Cancer
Authors: Tien Jean C-Y. , Liu Zhaoliang , Liao Lan , Wang Fen , Xu Yixiang , Wu Ye-Lin , Zhou Niya , Ittmann Michael , Xu Jianming
Published: May 2013

The transcriptional coactivator SRC-3 plays a key role in enhancing prostate cancer cell proliferation. Although SRC-3 is highly expressed in advanced prostate cancer, its role in castration-resistant prostate cancer (CRPC) driven by PTEN mutation is unknown. We documented elevated SRC-3 in human CRPC and in PTEN-negative human prostate cancer. Patients with high SRC-3 and undetectable PTEN exhibited decreased recurrence-free survival. To explore the causal relationship in these observations, we generated mice in which both Pten and SRC-3 were inactivated in prostate epithelial cells (Pten3CKO mice), comparing them with mice in which only Pten was inactivated in these cells (PtenCKO mice). SRC-3 deletion impaired cellular proliferation and reduced tumor size. Notably, while castration of PtenCKO control mice increased the aggressiveness of prostate tumors relative to noncastrated counterparts, deletion of SRC-3 in Pten3CKO mice reversed all these changes. In support of this finding, castrated Pten3CKO mice also exhibited decreased levels of phospho-Akt, S6 kinase (RPS6KB1), and phosphorylated S6 protein (RPS6), all of which mediate cell growth and proliferation. Moreover, these tumors appeared to be more differentiated as evidenced by higher levels of Fkbp5, an AR-responsive gene that inhibits Akt signaling. Lastly, these tumors also displayed lower levels of certain androgen-repressed genes such as cyclin E2 and MMP10. Together, our results show that SRC-3 drives CRPC formation and offer preclinical proof of concept for a transcriptional coactivator as a therapeutic target to abrogate CRPC progression. Cancer Res; 73(13); 3997–4008. ©2013 AACR.
Loss of ARF Sensitizes Transgenic BRAFV600E Mice to UV-Induced Melanoma via Suppression of XPC
Authors: Luo Chi , Sheng Jinghao , Hu Miaofen G. , Haluska Frank G. , Cui Rutao , Xu Zhengping , Tsichlis Philip N. , Hu Guo-Fu , Hinds Philip W.
Published: May 2013

Both genetic mutations and UV irradiation (UVR) can predispose individuals to melanoma. Although BRAFV600E is the most prevalent oncogene in melanoma, the BRAFV600E mutant is not sufficient to induce tumors in vivo. Mutation at the CDKN2A locus is another melanoma-predisposing event that can disrupt the function of both p16INK4a and ARF. Numerous studies have focused on the role of p16INK4a in melanoma, but the involvement of ARF, a well-known p53 activator, is still controversial. Using a transgenic BRAFV600E mouse model previously generated in our laboratory, we report that loss of ARF is able to enhance spontaneous melanoma formation and cause profound sensitivity to neonatal UVB exposure. Mechanistically, BRAFV600E and ARF deletion synergize to inhibit nucleotide excision repair by epigenetically repressing XPC and inhibiting the E2F4/DP1 complex. We suggest that the deletion of ARF promotes melanomagenesis not by abrogating p53 activation but by acting in concert with BRAFV600E to increase the load of DNA damage caused by UVR. Cancer Res; 73(14); 4337–48. ©2013 AACR.
Biliary Stent Therapy for Dominant Strictures in Patients Affected by Primary Sclerosing Cholangitis
Authors: Abu-Wasel Bassam , Keough Valerie , Renfrew Paul D. , Molinari Michele
Published: May 2013

The diagnosis and the treatment of dominant strictures (DS) in patients with primary sclerosing cholangitis (PSC) is challenging and the scientific literature on the subject is quite limited. Only level II and level III evidence is available to guide physicians managing patients with DS and PSC. For the diagnosis, intraductal endoscopic ultrasound is the most sensitive (64%) and specific (95%) test. However, the majority of cases require a combination of several different diagnostic tests, as there is no single investigation that can rule out malignancy in this group of patients. For the treatment, serial endoscopic or percutaneous dilatations provide 1- and 3-year biliary duct patency in 80 and 60% of patients, respectively. Dilatation and stenting are the most common interventions, although the optimal duration of treatment has still not been clearly defined. Bile duct resection and/or bilioenteric bypass are currently indicated only for patients with preserved liver function. For all other patients, benign DS can be treated with endoscopic dilatation with short-term stenting. This approach is effective and safe and does not increase the risk of malignant transformation or complications for liver transplant candidates. During the last decade, the use of self-expandable metallic stents for benign diseases has become an innovative option. The aim of this article is to review the diagnostic and therapeutic strategies for patients affected by PSC and DS with specific emphasis on the outcomes of patients treated with temporary stents.
Update on Zinc Deficiency and Excess in Clinical Pediatric Practice
Authors: Krebs Nancy F.
Published: May 2013

The critical importance of adequate zinc status to human health, including normal growth and development, is indisputable. The high prevalence of zinc deficiency on a global basis and its importance to public health have been well documented through large-scale randomized controlled zinc supplementation trials. Similar evidence in the clinical setting, however, is much less widely available due to the nonspecific features of zinc deficiency and to the lack of sensitive biomarkers to detect zinc deficiency, especially that of a mild degree of severity. The current understanding of zinc homeostasis indicates that the primary determinants of zinc absorption are the amount of zinc ingested and dietary phytate, the latter having a major effect on zinc bioavailability. In normal as well as in many pathologic conditions, the gastrointestinal tract is the major site of zinc losses resulting from secretion of endogenous zinc into the lumen and subsequent excretion in the feces. The amount excreted is dependent on host status, the amount reabsorbed, and sometimes the presence of pathophysiologic conditions, including diarrhea and steatorrhea. Assessment in the clinical setting dictates that the clinician obtain a careful medical and diet history, recognize clinical presentations in which zinc adequacy may be compromised, and link this risk with nonspecific but plausible manifestations of deficiency. Examples discussed in this article include primary zinc deficiency due to dietary inadequacy (older breastfed infants or toddlers without zinc-rich complementary foods); genetically based deficiency (acrodermatitis enteropathica, acquired zinc deficiency of lactogenic origin), and acquired secondary deficiency in low birth weight and prematurity, gastrointestinal and hepatic disease, and cystic fibrosis. Evidence for efficacy of zinc therapy with pharmacologic doses for two conditions, Wilson's disease and viral upper respiratory infections, is also discussed.
Systematic Review of Zinc Fortification Trials
Authors: Das Jai K. , Kumar Rohail , Salam Rehana A. , Bhutta Zulfiqar A.
Published: May 2013

Zinc is one of the essential trace elements required by the human body as it is present in more than a hundred specific enzymes and serves as an important structural ion in transcription factors. Around one third of the world population lives in countries with a high prevalence of zinc deficiency. Food fortification with zinc seems to be an attractive public health strategy and a number of programs have been initiated, especially in developing countries. We conducted a systematic review to assess the efficacy of zinc fortification. A total of 11 studies with 771 participants were included in our analysis. Zinc fortification was associated with significant improvements in plasma zinc concentrations [standard mean difference (SMD) 1.28, 95% CI 0.56, 2.01] which is a functional indicator of zinc status. Significant improvement was observed for height velocity (SMD 0.52, 95% CI 0.01, 1.04); however, this finding was weak and based on a restricted analysis. Further subgroup analysis showed significant improvement in height velocity among very-low-birth-weight infants (SMD 0.70, 95% CI 0.02, 1.37), while for healthy newborns, the impact was insignificant. Zinc fortification had insignificant impacts on serum alkaline levels, serum copper levels, hemoglobin and weight gain. Although the findings highlight that zinc fortification is associated with an increased serum concentration of the micronutrient, overall evidence of the effectiveness of this approach is limited. Data on pregnant and lactating women is scarce. Large-scale fortification programs with robust impact assessment should be initiated to cover larger populations in all age groups. Mass fortification of zinc may be a cost-effective strategy to overcome zinc deficiency.
Update on Zinc Biology
Authors: Solomons Noel W.
Published: May 2013

Zinc has become a prominent nutrient of clinical and public health interest in the new millennium. Functions and actions for zinc emerge as increasingly ubiquitous in mammalian anatomy, physiology and metabolism. There is undoubtedly an underpinning in fundamental biology for all of the aspects of zinc in human health (clinical and epidemiological) in pediatric and public health practice. Unfortunately, basic science research may not have achieved a full understanding as yet. As a complement to the applied themes in the companion articles, a selection of recent advances in the domains homeostatic regulation and transport of zinc is presented; they are integrated, in turn, with findings on genetic expression, intracellular signaling, immunity and host defense, and bone growth. The elements include ionic zinc, zinc transporters, metallothioneins, zinc metalloenzymes and zinc finger proteins. In emerging basic research, we find some plausible mechanistic explanations for delayed linear growth with zinc deficiency and increased infectious disease resistance with zinc supplementation.
Effect of Prolonged Tacrolimus Treatment in Idiopathic Membranous Nephropathy with Nephrotic Syndrome
Authors: Yuan Hang , Liu Nian , Sun Guang-Dong , Jia Ye , Luo Ping , Miao Li-Ning
Published: May 2013

Objective: Tacrolimus has been used for idiopathic membranous nephropathy (IMN) therapy, but most patients who achieved remission showed a high relapse rate when tacrolimus was withdrawn after 6-12 months of therapy. We proposed that a prolonged therapeutic course should help reduce the relapse rate. Methods: A total of 42 patients with nephrotic syndrome caused by IMN were randomly divided into short-term (n = 20) and long-term (n = 22) groups. All patients received initial treatment with tacrolimus and prednisone for 6 months, and afterward only the long-term patient group was tapered with low-dose tacrolimus until 24 months. Results: Over 85% of the patients achieved proteinuria reduction, serum albumin improvement and serum lipid recovery; the probability of remission in both groups was over 80% at 6 months. The remission rate was steady at over 80% after 12 and 24 months in the long-term group, but only 50 and 45%, respectively, in the short-term group. Nine patients (45%) relapsed in the short-term group after tacrolimus withdrawal, while not a single patient suffered recurrence in the long-term group. The concentration of tacrolimus remained similar between the two groups at 5-8 ng/ml during the initial 6 months, and was significantly decreased at 12 months compared to 6 months (p < 0.05), along with reduction of oral administration in the long-term group. Conclusion: Combined therapy of tacrolimus with prednisone can relieve IMN significantly; prolonged tacrolimus treatment at a low blood concentration can alleviate the illness persistently, with a low recurrence rate and gratifying safety.
A Prospective Study on 132 Cases of Ocular Palsy
Authors: Castelluccia A. , Nociti V. , Frisullo G. , Batocchi A.P.
Published: May 2013

Objectives: In this prospective study, we used one diagnostic protocol to establish an early diagnosis in patients with ocular palsies in absence of other neurological findings. Materials and Methods: The study was performed on a consecutive series of 132 patients who visited our Neurological Department for ptosis and/or diplopia in absence of other neurological signs, using the same diagnostic protocol. Results: An etiological diagnosis was made in 74% of cases during a mean time of 17 ± 23 months from symptom onset. Myasthenia gravis was the most common diagnosis (n = 60, 45.5%). Thirty-four cases (26%) remained undiagnosed in spite of a follow-up lasting 32 ± 33 months on average. Conclusions: Identifying the cause of an isolated ocular palsy can be difficult, and an extended follow-up time does not aid in further establishment of the diagnosis.
The Effect of Solifenacin on Cognitive Function following Stroke
Authors: Park Jin-Woo
Published: May 2013

Background/Aims: Our aim was to investigate the effect of solifenacin (an anticholinergic) on cognitive function after stroke. Methods: We retrospectively reviewed 66 stroke cases who were prescribed solifenacin for more than 2 months. A control group was generated matching the patients both for sex and age. The interval changes in the Mini-Mental State Examination (MMSE) score and Clinical Dementia Rating Sum of Boxes (CDR-SB) score after solifenacin administration were compared to those of the control group. Results: The baseline MMSE score of the control group was 15.9 ± 9.2 and that of the solifenacin group was 14.3 ± 7.8. After using solifenacin for an average of 76.9 days, there was a change in the MMSE score of 1.9 ± 5.2. During similar periods, there was a change in the MMSE score of 2.9 ± 3.7 in the control group (not using solifenacin). However, there was no significant difference between the two groups. Similarly, there was no significant difference in the CDR-SB score between the two groups. Conclusion: Solifenacin treatment did not affect the short-term cognitive performance in stroke patients. This information might be useful when prescribing anticholinergics to stroke patients.
Arterial Stiffness and Walk Time in Patients with End-Stage Renal Disease
Authors: Lane Abbi D. , Wu Pei-Tzu , Kistler Brandon , Fitschen Peter , Tomayko Emily , Jeong Jin-Hee , Chung Hae Ryung , Yan Huimin , Ranadive Sushant M. , Phillips Shane , Fernhall Bo , Wilund Kenneth
Published: May 2013

Background: End-stage renal disease patients experience increased prevalence of cardiovascular disease. Heart-artery interaction may be shifted, impacting blood pressure lability, and exercise tolerance. The coupling ratio consists of the ratio of indexed arterial elastance (EaI, arterial load) to ElvI, a measure of cardiac contractility or stiffness. Our purpose was to explore the relationship between elastances and functional capacity. We hypothesized that arterial stiffness (central pulse wave velocity, PWV) and elastances would be correlated to shuttle walk time. Methods: We used applanation tonometry, ultrasonography, and a shuttle walk test to evaluate our hypothesis. Spearman's correlations were used to assess relationships between variables. Block regression was also performed. Results: Forty-two subjects on maintenance hemodialysis participated. Average age=44±5 years, body surface area=2.01 kg/m2. Mean EaI=4.45 and mean ElvI=6.89; the coupling ratio=0.82. Mean aortic pulse pressure=51 mmHg and PWV=9.6 m/s. PWV(r=-0.385) and EaI (r=-0.424) were significantly and inversely related to walking time while stroke volume index (SVI) was positively correlated to shuttle walk time (r=0.337), p<0.05 for all. Conclusions: We conclude that, like other clinical populations, both arterial and heart function predict walking ability and represent potential targets for intervention; arterial stiffness and SVI are strongly related to shuttle walk time in patients with ESRD.
Prognosis of Dialysed Patients after Kidney Transplant Failure
Authors: Szabó Réka P. , Klenk Nóra , Balla József , Asztalos László , Szabó László , Vokó Zoltán
Published: May 2013

Background/Aims: Patients with a failed kidney transplant represent a unique, high-risk chronic kidney disease population that is increasing in number, and may be sub-optimally managed. Our aim was to compare the survival of patients with failed allografts to patients with native kidney failure and to assess whether their survival is affected by the graft resection. Methods: Kaplan-Meier and Cox-regression survival analyses were performed on the data of 57 patients with graft failure and of 123 transplant-naive haemodialysed patients. Results: After adjustment for age and gender, there was no statistically significant difference in the mortality of patients in the two groups. The 43 patients, who had a transplanted kidney nephrectomy had a statistically not significant survival benefit over non-nephrectomised patients (age and gender adjusted hazard ratio: 0.56 95 % confidence interval: 0.24-1.58, p-value: 0.18). Conclusion: Elective graft resection is a safe, effective alternative for both the treatment and the prevention of the chronic inflammatory state associated with a failed kidney transplant.
Linked 5S and 45S rDNA Sites Are Highly Conserved through the Subfamily Aurantioideae (Rutaceae)
Authors: Barros e Silva A.E. , dos Santos Soares Filho W. , Guerra M.
Published: May 2013

Sites of 5S and 45S rDNA are more commonly located on different chromosomes of most angiosperms. Previous investigations have shown that in the subfamily Aurantioideae these sites may appear closely linked (adjacent sites), as in Poncirustrifoliata, or completely isolated, as in some species of Citrus. In the present work, the distribution of rDNA sites was investigated in representatives of 9 genera of Aurantioideae by FISH and CMA banding, aiming to understand the evolution of adjacent sites in the subfamily. A total of 57 rDNA sites were observed, 40 of them being adjacent to each other. All adjacent sites displayed the 45S rDNA array more terminally located. Assuming that the linked 5S-45S rDNA arrangement was the ancestral condition in Aurantioideae, the isolated rDNA sites observed in Clausena excavata,Bergera koenigii, and Fortunella obovata, as well as the complete linkage loss in Citrus maxima and C. medica indicates that unlinked sites arose independently several times in the evolution of the group. The linkage loss may be due to independent dispersion of one or both rDNA sequence families followed by deletion of the corresponding array in the adjacent site. The possible mechanisms behind these events and their occurrence in other groups are discussed.
Assessment of the Macula in Keratoconus: An Optical Coherence Tomography and Multifocal Electroretinography Study
Authors: Moschos Marilita M. , Chatziralli Irini P. , Koutsandrea Chryssanthi , Siasou Georgia , Droutsas Dimitrios
Published: May 2013

Purpose: The purpose of our study was to assess the macular thickness and the electrophysiological changes in keratoconic patients without any systemic or ocular disorders. Methods: 64 eyes of 32 keratoconus patients as well as 60 eyes of 30 controls participated in the study. All participants underwent a complete ophthalmological examination, including best-corrected visual acuity (BCVA) assessment, color vision testing, fundus examination, intraocular pressure measurement, central foveal thickness (CFT) measurement by optical coherence tomography (OCT) scan, and multifocal-electroretinogram (mf-ERG) recording. CFT, retinal response density (RRD) and P1 latency were measured. Results: There was no statistically significant difference between the two groups concerning CFT and P1 latency in mf-ERG. The RRD in mf-ERG differed significantly between keratoconus patients and controls. Of note, BCVA was positively associated with RRD in keratoconus patients. Conclusion: In some cases of keratoconus, a macular dysfunction not visible ophthalmoscopically may coexist and the low visual acuity could be due not only to the corneal abnormality, but also to the photoreceptor dysfunction. As a result, the preoperative electrophysiological study of patients with keratoconus is crucial to avoid a needless corneal transplantation.
Removal of Protein-Bound Uraemic Toxins by Haemodialysis
Authors: Niwa Toshimitsu
Published: May 2013

Accumulating evidence suggests that protein-bound uraemic toxins play an important role in uraemic complications, especially in cardiovascular disease. Notably, protein-bound uraemic toxins such as indoxyl sulphate, p-cresyl sulphate, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) have emerged as important targets of therapeutic removal. Indoxyl sulphate stimulates reactive oxygen species production in human umbilical vein endothelial cells (HUVEC) most intensely, followed by CMPF. Indoxyl sulphate and CMPF inhibit cell growth of HUVEC. Haemodialysis (HD) even with a high-flux membrane cannot efficiently remove the protein-bound uraemic toxins because of their high albumin-binding property. Especially, indoxyl sulphate, p-cresyl sulphate, and CMPF showed high protein-binding ratios (more than 95%) and low reduction rates by HD (less than 35%). Removal of indoxyl sulphate and p-cresyl sulphate can be improved to some extent by increasing the diffusion of the free forms with super-flux membrane HD, increasing the dialyzer mass transfer area coefficient and dialysate flow, haemodiafiltration, daily HD, and addition of a sorbent to dialysate. However, CMPF is more strongly bound to albumin (with a binding ratio of 99-100%) than indoxyl sulphate and p-cresyl sulphate, and cannot be removed at all by conventional HD. Uraemic toxins strongly or covalently bound to albumin such that CMPF can be removed by protein-leaking HD. Protein-leaking HD with a polymethylmethacrylate membrane BK-F dialyzer can reduce serum levels of CMPF with improvement of anaemia as well as reduce plasma levels of homocysteine, pentosidine, and inflammatory cytokines.
Prurigo Nodularis and Dialyzer Membrane
Authors: Goeksel Tugce , Xie Wenhao , Ritzerfeld Maria , Heidenreich Stefan , Mann Helmut
Published: May 2013

Prurigo nodularis is a skin disease with unknown origin which is frequent in patients on maintenance renal replacement therapy. Here, we report a patient who was dialyzed for more than 10 years with different dialyzers using different dialyzer membranes. Each time when the patient was switched to a polymethylmethacrylate membrane (Filtryzer BK-1.6P), itching and skin lesions disappeared completely. This effect could be verified three times.
The Use of Haplotypes in the Identification of Interaction between SNPs
Authors: Ken-Dror Gie , Humphries Steve E. , Drenos Fotios
Published: May 2013

Although haplotypes can provide great insight into the complex relationships between functional polymorphisms at a locus, their use in modern association studies has been limited. This is due to our inability to directly observe haplotypes in studies of unrelated individuals, but also to the extra complexity involved in their analysis and the difficulty in identifying which is the truly informative haplotype. Using a series of simulations, we tested a number of different models of a haplotype carrying two functional single nucleotide polymorphisms (SNPs) to assess the ability of haplotypic analysis to identify functional interactions between SNPs at the same locus. We found that, when phase is known, analysis of the haplotype is more powerful than analysis of the individual SNPs. The difference between the two approaches becomes less either as an increasing number of non-informative SNPs are included, or when the haplotypic phase is unknown, while in both cases the SNP association becomes progressively better at identifying the association. Our results suggest that when novel genotyping and bioinformatics methods are available to reconstruct haplotypic phase, this will permit the emergence of a new wave of haplotypic analysis able to consider interactions between SNPs with increased statistical power.
Clinically Relevant Effect of a New Intranasal Therapy (MP29-02) in Allergic Rhinitis Assessed by Responder Analysis
Authors: Meltzer Eli , Ratner Paul , Bachert Claus , Carr Warner , Berger William , Canonica G. Walter , Hadley James , Lieberman Phil , Hampel Frank C. , Mullol Joaquim , Munzel Ullrich , Price David , Scadding Glenis , Virchow J. Christian , Wahn Ulrich , Murray Ruth , Bousquet Jean
Published: May 2013

Background: It is unclear what constitutes a clinically meaningful response for allergic rhinitis (AR) outcomes. The objectives of these post hoc analyses were (1) to define a clinically meaningful response using novel efficacy analyses (including a responder analysis), and (2) to compare the efficacy of MP29-02 [a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP)] with commercially available FP, AZE and placebo in seasonal AR (SAR) patients, using these novel analyses. Methods: 610 moderate-to-severe SAR patients (≥12 years old) were randomized into a double-blind, placebo-controlled, 14-day, parallel-group trial. Change from baseline in the reflective total nasal symptom score (rTNSS) over 14 days was the primary outcome. Post hoc endpoints included the sum of nasal and ocular symptoms (rT7SS), efficacy by disease severity and by predominant nasal symptom, and a set of responder analyses. Results: MP29-02 most effectively reduced rT7SS (relative greater improvement: 52% to FP; 56% to AZE) and both nasal and ocular symptoms irrespective of severity. More MP29-02 patients achieved a ≥30, ≥50, ≥60, ≥75 and ≥90% rTNSS reduction, which occurred days faster than with either active comparator; MP29-02 alone was superior to placebo at the ≥60% (or higher) threshold. One in 2 MP29-02 patients achieved a ≥50% rTNSS reduction and 1 in 6 achieved complete/near-to-complete response. Only MP29-02 was consistently superior to placebo for all patients, whatever their predominant symptom. Conclusions: MP29-02 provided faster and more complete symptom control than first-line therapies. It was consistently superior irrespective of severity, response criteria or patient-type, and may be considered the drug of choice for moderate-to-severe AR. These measures define a new standard for assessing relevance in AR.
Disseminated Mucormycosis in a Patient with Recent Kidney Transplantation: A Case Report and Review of the Literature
Authors: Hatahet Mohamad Hazem , Narayanan Mohanram , Cleaves Constance , Zreik Riyam
Published: May 2013

Mucormycosis is an invasive fungal infection commonly seen in diabetics and immunocompromised patients. We report a case of disseminated mucormycosis in a 47-year-old diabetic male who underwent deceased donor renal allograft transplantation about 5 weeks prior to presentation. Our patient presented with increasing fatigue, diarrhea and oligoanuria and was found to have significant acute kidney injury. Doppler ultrasound of the allograft revealed segmental decreased renal perfusion in the upper pole of the allograft with moderate hydronephrosis. Nephrostomy tube placement yielded minimal urine output. An allograft biopsy showed diffuse C4d-positive staining and fungal hyphae suggestive of Mucor infection. Computed tomography (CT) imaging revealed a right upper lobe mass, a small hypodensity in the liver and normal findings in the head. Despite prompt management including discontinuation of immunosuppression, amphotericin B and allograft nephrectomy, the patient had a rapid decompensation, developed respiratory failure requiring intubation, hypotension and supraventricular tachycardia with multiple new areas of hypoattenuation on head CT - all of which ultimately resulted in his death. A review of the literature revealed that mucormycosis is a relatively rare disease with a cumulative 12-month incidence rate of 0.07% in solid organ transplant recipients. Disseminated disease was found in about 23% of cases, with a mortality rate of 96%.
Cardiac Resynchronization Therapy Improves Altered Na Channel Gating in Canine Model of Dyssynchronous Heart Failure
Authors: Aiba Takeshi , Barth Andreas S. , Hesketh Geoffrey G. , Hashambhoy Yasmin L. , Chakir Khalid , Tunin Richard S. , Greenstein Joseph L. , Winslow Raimond L. , Kass David A. , Tomaselli Gordon F.
Published: May 2013

Background—

Slowed Na
+
current (
I
Na
) decay and enhanced late
I
Na
(
I
Na-L
) prolong the action potential duration (APD) and contribute to early afterdepolarizations. Cardiac resynchronization therapy (CRT) shortens APD compared with dyssynchronous heart failure (DHF); however, the role of altered Na
+
channel gating in CRT remains unexplored.

Methods and Results—

Adult dogs underwent left-bundle branch ablation and right atrial pacing (200 beats/min) for 6 weeks (DHF) or 3 weeks followed by 3 weeks of biventricular pacing at the same rate (CRT).
I
Na
and
I
Na-L
were measured in left ventricular myocytes from nonfailing, DHF, and CRT dogs. DHF shifted voltage-dependence of
I
Na
availability by −3 mV compared with nonfailing, enhanced intermediate inactivation, and slowed recovery from inactivation. CRT reversed the DHF-induced voltage shift of availability, partially reversed enhanced intermediate inactivation but did not affect DHF-induced slowed recovery. DHF markedly increased
I
Na-L
compared with nonfailing. CRT dramatically reduced DHF-induced enhanced
I
Na-L
, abbreviated the APD, and suppressed early afterdepolarizations. CRT was associated with a global reduction in phosphorylated Ca
2+
/Calmodulin protein kinase II, which has distinct effects on inactivation of cardiac Na
+
channels. In a canine AP model, alterations of
I
Na-L
are sufficient to reproduce the effects on APD observed in DHF and CRT myocytes.

Conclusions—

CRT improves DHF-induced alterations of Na
+
channel function, especially suppression of
I
Na-L
, thus, abbreviating the APD and reducing the frequency of early afterdepolarizations. Changes in the levels of phosphorylated Ca
2+
/Calmodulin protein kinase II suggest a molecular pathway for regulation of
I
Na
by biventricular pacing of the failing heart.
Interaction Between Chromosome 2 and 3 Regulates Pulse Pressure in the Stroke-Prone Spontaneously Hypertensive Rat
Authors: Koh-Tan H.H. Caline , McBride Martin W. , McClure John D. , Beattie Elisabeth , Young Barbara , Dominiczak Anna F. , Graham Delyth
Published: May 2013

In an F2 cross between stroke-prone spontaneously hypertensive (SHRSP) and Wistar Kyoto (WKY) rats, we previously identified blood pressure quantitative trait loci (QTL) on rat chromosome (RNO) 2 and a pulse pressure QTL on RNO3. The aims of this study were to confirm the QTL on RNO3 and to investigate interaction between RNO2 and RNO3 loci through the generation and phenotypic assessment of single RNO3 congenic (SP.WKY
Gla
3a) and bicongenic (SP.WKY
Gla
2a/3a) strains. Hemodynamic profiling, vascular function, and renal histology were examined in these newly generated strains along with the previously reported RNO2 congenic strain (SP.WKY
Gla
2a). Our results demonstrate significant equivalent reduction in systolic, diastolic, and pulse pressure phenotypes in SP.WKY
Gla
3a and SP.WKY
Gla
2a rats, whereas greater reductions were observed with the SP.WKY
Gla
2a/3a bicongenic strain achieving blood pressure levels similar to normotensive WKY rats. Epistasis was observed between pulse pressure QTL on RNO2 and 3 at baseline and during 1% salt challenge. Vascular function and renal pathology studies indicate that QTL on RNO3 are responsible for salt-induced kidney pathology, whereas QTL on RNO2 seem to have greater impact on vascular function. RNO3 congenic and bicongenic strains have confirmed the importance of SHRSP alleles in the RNO3 congenic interval on pulse pressure variability and end-organ damage. These strains will allow interrogation of complex gene–gene and gene–environment interactions contributing to salt-sensitive hypertension and renal pathology in the SHRSP rat.
Determinants of Progression of Aortic Stiffness in Hemodialysis Patients
Authors: Utescu Mihai S. , Couture Véronique , Mac-Way Fabrice , De Serres Sacha A. , Marquis Karine , Larivière Richard , Desmeules Simon , Lebel Marcel , Boutouyrie Pierre , Agharazii Mohsen
Published: May 2013

Aortic stiffness is associated with increased cardiovascular mortality in patients with chronic kidney disease. However, the rate of progression of arterial stiffness and the role of cardiovascular risk factors in the progression of arterial stiffness has never been established in a longitudinal study. In a prospective, longitudinal, observational study, carotid-femoral pulse wave velocity and carotid-radial pulse wave velocity were assessed in 109 hemodialysis patients at baseline and after a mean follow-up of 1.2 years. We examined the impact of age, atherosclerotic cardiovascular disease, diabetes mellitus, dialysis vintage, and pentosidine (a well-characterized, advanced glycation end products) on the rate of progression of aortic stiffness. The annual rate of changes in carotid-femoral pulse wave velocity and carotid-radial pulse wave velocity were 0.84 m/s per year (95% confidence interval, 0.50–1.12 m/s per year) and −0.66 m/s per year (95% confidence interval, −0.85 to −0.47 m/s per year), respectively. Older subjects, and patients with diabetes mellitus or atherosclerotic cardiovascular disease had higher aortic stiffness at baseline, however, the rate of progression of aortic stiffness was only determined by plasma pentosidine levels (
P
=0.001). The degree of baseline aortic stiffness was a significant determinant of the regression of brachial stiffness (
P
<0.001) suggesting that the regression of brachial stiffness occurs in response to central aortic stiffness. These findings suggest that traditional cardiovascular risk factors may play some role in the progression of aortic stiffness before development of advanced chronic kidney disease, and that the enhanced rate of progression of aortic stiffness in chronic kidney disease patients on dialysis are probably determined by more specific chronic kidney disease–related risk factors such as advanced-glycation end products.
Long-Term Control of Arterial Hypertension and Regression of Left Ventricular Hypertrophy With Treatment of Primary Aldosteronism
Authors: Rossi Gian Paolo , Cesari Maurizio , Cuspidi Cesare , Maiolino Giuseppe , Cicala Maria Verena , Bisogni Valeria , Mantero Franco , Pessina Achille C.
Published: May 2013

Primary aldosteronism (PA), a common cause of high blood pressure (BP), induces left ventricular (LV) hypertrophy and an excess rate of cardiovascular events. Whether its treatment provides long-term cure of hypertension and regression of cardiovascular damage remains uncertain. To the aim of assessing the effect of treatment of PA on BP and LV changes, we prospectively recruited 323 patients in a long-term follow-up study entailing serial echocardiography evaluations. Of them, 180 had PA and were assigned to either adrenalectomy (n=110) or medical therapy (n=70) on the basis of the adrenal vein sampling. The remaining 143 were consecutive optimally treated primary hypertensive patients. At baseline, the PA patients had more inappropriate LV mass than PH patients (27.1% versus 16.2%;
P
=0.020), despite similar BP values. At a median follow-up of 36 months (range, 6–225), BP was lowered (
P
<0.0001 versus baseline) to similar values in adrenalectomized (135±15/83±9 mm Hg), medically treated PA (133±11/83±7 mm Hg), and PH (139±15/86±9 mm Hg) patients. To this end, the adrenalectomized patients required significantly less drugs than the other groups. In PA patients, the LV mass index and the rate of LV hypertrophy fell through LV inward remodeling to the level of optimally treated PH patients, indicating that the LV work markedly decreased. Findings were similar when long-term (≥5 and ≥10 years) data were examined. Thus, an early diagnosis and a specific treatment of PA warrant normalization of BP and reversal of detrimental LV changes at long term.
Functional Role of TRPV4-K
Ca
2.3 Signaling in Vascular Endothelial Cells in Normal and Streptozotocin-Induced Diabetic Rats
Authors: Ma Xin , Du Juan , Zhang Peng , Deng Jianxin , Liu Jie , Lam Francis Fu-Yuen , Li Ronald A. , Huang Yu , Jin Jian , Yao Xiaoqiang
Published: May 2013

The small conductance and intermediate conductance Ca
2+
-activated K
+
channels are known to be involved in the endothelium-dependent hyperpolarization. Ca
2+
entry into endothelial cells stimulates these channels, causing membrane hyperpolarization in endothelial cells and underlying smooth muscle cells. In the present study, with the use of coimmunoprecipitation and double immunolabeling methods, we demonstrated a physical interaction of transient receptor potential vanilloid 4 (TRPV4) with K
Ca
2.3 in rat mesenteric artery endothelial cells. Acetylcholine and 4α-PDD mainly acted through TRPV4-K
Ca
2.3 pathway to induce smooth muscle hyperpolarization and vascular relaxation. K
Ca
3.1 was also involved in the process but at a much lesser degree than that of K
Ca
2.3. Stimulating TRPV4-K
Ca
2.3 signaling pathway also increased local blood flow in mesenteric beds and reduced systemic blood pressure in anesthetized rats. In streptozotocin-induced diabetic rats, the expression levels of TRPV4 and K
Ca
2.3 were reduced, which could be an underlying reason for the dysfunction of endothelium-dependent hyperpolarization in these animals. These results demonstrated an important physiological and pathological role of TRPV4-K
Ca
2.3 signaling pathway in vascular endothelial cells.
Buccinator Myomucosal Flap for Reconstruction of Glossectomy Defects
Authors: Woo Seung Hoon , Jeong Han‐Sin , Kim Jin Pyeong , Park Jung Je , Ryu Junsun , Baek Chung‐Hwan
Published: May 2013

Objective

The use of the myomucosal flap from the buccinator muscle is a valuable reconstruction method for intraoral defects. We report the clinical advantages and pitfalls of using the buccinator myomucosal flap for tongue reconstruction after intraoral resection of tongue cancer.

Study Design

Prospective study.

Setting

University hospital.

Subjects and Methods

We used buccal artery–based buccinator myomucosal flaps for tongue reconstruction in 11 partial or total edentulous patients who underwent resection of tongue cancer. The size and site of the tongue defect ranged from one‐third to one‐half of the tongue in the lateral border. We analyzed the clinical features and oncologic and functional outcomes to define adequate indications.

Results

All flaps were successfully harvested and transposed, and the donor sites were primarily closed. The pedicles were safely divided 2 to 3 weeks postoperatively. In 8 of 11 patients, concurrent upper neck dissection was performed without compromising blood supply to the flap. The range of tongue motion and the volume of the reconstructed tongue were satisfactory, and the patients experienced no difficulties in swallowing or speech.

Conclusion

Particularly in edentulous patients, the buccal myomucosal flap can be a good option for reconstructing partial tongue defects after cancer surgery.