bluuebunny/crossref_metadata_2025 huggingface dataset:
Voluntary wheel running in mice increases the rate of neurogenesis without affecting anxiety-related behaviour in single tests
Authors: Garrett Lillian , Lie D Chichung , Hrabé de Angelis Martin , Wurst Wolfgang , Hölter Sabine M
Published: June 2012

Background

The role played by adult neurogenesis in anxiety is not clear. A recent study revealed a surprising positive correlation between increased anxiety and elevated neurogenesis following chronic voluntary wheel running and multiple behavioural testing in mice, suggesting that adult hippocampal neurogenesis is involved in the genesis of anxiety. To exclude the possible confounding effect of multiple testing that may have occurred in the aforementioned study, we assessed (1) the effects of mouse voluntary wheel running (14 vs. 28 days) on anxiety in just one behavioural test; the open field, and (2), using different markers, proliferation, differentiation, survival and maturation of newly born neurons in the dentate gyrus immediately afterwards. Effects of wheel running on anxiety-related behaviour were confirmed in a separate batch of animals tested in another test of anxiety, the light/dark box test.

Results

Running altered measures of locomotion and exploration, but not anxiety-related behaviour in either test. 14 days running significantly increased proliferation, and differentiation and survival were increased after both running durations. 28 day running mice also exhibited an increased rate of maturation. Furthermore, there was a significant positive correlation between the amount ofproliferation, but not maturation, and anxiety measures in the open field of the 28 day running mice.

Conclusions

Overall, this evidence suggests that without repeated testing, newly bornmature neuronsmay not be involved in the genesis of anxietyper se.
Downregulation of alpha7 nicotinic acetylcholine receptor in two-kidney one-clip hypertensive rats
Authors: Chen Ji-Kuai , Zhao Ting , Ni Min , Li Dong-Jie , Tao Xia , Shen Fu-Ming
Published: June 2012

Background

Inflammation processes are important participants in the pathophysiology of hypertension and cardiovascular diseases. The role of the alpha7 nicotinic acetylcholine receptor (α7nAChR) in inflammation has recently been identified. Our previous study has demonstrated that the α7nAChR-mediated cholinergic anti-inflammatory pathway is impaired systemically in the genetic model of hypertension. In this work, we investigated the changes of α7nAChR expression in a model of secondary hypertension.

Methods

The 2-kidney 1-clip (2K1C) hypertensive rat model was used. Blood pressure, vagus nerve function, serum tumor necrosis factor-α (TNF-α) and both the mRNA and protein levels of α7nAChR in tissues from heart, kidney and aorta were measured at 4, 8 and 20 weeks after surgery.

Results

Compared with age-matched control, it was found that vagus nerve function was significantly decreased in 2K1C rats with the development of hypertension. Serum levels of TNF-α were greater in 2K1C rats than in age-matched control at 4, 8 and 20 weeks. α7nAChR mRNA in the heart was not altered in 2K1C rats. In the kidney of 2K1C rats, α7nAChR expression was significantly decreased at 8 and 20 weeks, but markedly increased at 4 weeks. α7nAChR mRNA was less in aorta of 2K1C rats than in age-matched control at 4, 8 and 20 weeks. These findings were confirmed at the protein levels of α7nAChR.

Conclusions

Our results suggested that secondary hypertension may induce α7nAChR downregulation, and the decreased expression of α7nAChR may contribute to inflammation in 2K1C hypertension.
A classical phenotype of Anderson-Fabry disease in a female patient with intronic mutations of the GLA gene: a case report
Authors: Pisani Antonio , Imbriaco Massimo , Zizzo Carmela , Albeggiani Giuseppe , Colomba Paolo , Alessandro Riccardo , Iemolo Francesco , Duro Giovanni
Published: June 2012

Background

Fabry disease (FD) is a hereditary metabolic disorder caused by the partial or total inactivation of a lysosomal hydrolase, the enzyme α-galactosidase A (GLA). This inactivation is responsible for the storage of undegraded glycosphingolipids in the lysosomes with subsequent cellular and microvascular dysfunction. The incidence of disease is estimated at 1:40,000 in the general population, although neonatal screening initiatives have found an unexpectedly high prevalence of genetic alterations, up to 1:3,100, in newborns in Italy, and have identified a surprisingly high frequency of newborn males with genetic alterations (about 1:1,500) in Taiwan.

Case presentation

We describe the case of a 40-year-old female patient who presented with transient ischemic attack (TIA), discomfort in her hands, intolerance to cold and heat, severe angina and palpitations, chronic kidney disease. Clinical, biochemical and molecular studies were performed.

Conclusions

Reported symptoms, peculiar findings in a renal biopsy – the evidence of occasional lamellar inclusions in podocytes and mesangial cells – and left ventricular (LV) hypertrophy, which are considered to be specific features of FD, as well as molecular evaluations, suggested the diagnosis of a classical form of FD.

We detected four mutations in the GLA gene of the patient: -10C>T (g.1170C>T), c.370-77_-81del (g.7188-7192del5), c.640-16A>G (g.10115A>G), c.1000-22C>T (g.10956C>T). These mutations, located in promoter and intronic regulatory regions, have been observed in several patients with manifestations of FD. In our patient clinical picture showed a multisystemic involvement with early onset of symptoms, thus suggesting that these intronic mutations can be found even in patients with classical form of FD.
HIV and HCV prevalence among entrants to methadone maintenance treatment clinics in China: a systematic review and meta-analysis
Authors: Zhuang Xun , Liang Yanxian , Chow Eric PF , Wang Yafei , Wilson David P , Zhang Lei
Published: June 2012

Background

Methadone maintenance treatment (MMT) was implemented in China since 2004. It was initiated in 8 pilot clinics and subsequently expanded to 738 clinics by the end of 2011. Numerous individual research studies have been conducted to estimate HIV and HCV prevalence among MMT clients but an overview of the epidemics in relations to MMT remains unclear. The aim of this study is to estimate the magnitude and changing trends of HIV, HCV and HIV-HCV co-infections among entry clients to MMT clinics in China during 2004-2010.

Methods

Chinese and English databases of literature were searched for studies reporting HIV, HCV and co-infection prevalence among MMT clients in China from 2004 to 2010. The prevalence estimates were summarized through a systematic review and meta-analysis of published literatures.

Results

Ninety eligible articles were selected in this review (2 in English and 88 in Chinese). Nationally, pooled prevalence of HIV-HCV and HIV-HCV co-infection among MMT clients was 6.0% (95%CI: 4.7%-7.7%), 60.1% (95%CI: 52.8%-67.0%) and 4.6% (95%CI: 2.9%-7.2%), respectively. No significant temporal trend was found in pooled prevalence estimates. Study location is the major contributor of heterogeneities of both HIV and HCV prevalence among drug users in MMT.

Conclusions

There was no significant temporal trend in HIV and HCV prevalence among clients in MMT during 2004–2010. Prevalence of HCV is markedly higher than prevalence of HIV among MMT clients. It is recommended that health educational programs in China promote the earlier initiation and wider coverage of MMT among injecting drug users (IDUs), especially HIV-infected IDUs.
Experimental in vivo and in vitro treatment with a new histone deacetylase inhibitor belinostat inhibits the growth of pancreatic cancer
Authors: Dovzhanskiy Dmitriy I , Arnold Stefanie M , Hackert Thilo , Oehme Ina , Witt Olaf , Felix Klaus , Giese Nathalia , Werner Jens
Published: June 2012

Background

Treatment options for pancreatic ductal adenocarcinoma (PDAC) are limited. Histone deacetylase inhibitors are a new and promising drug family with strong anticancer activity. The aim of this study was to examine the efficacy of in vitro and in vivo treatment with the novel pan-HDAC inhibitor belinostat on the growth of human PDAC cells.

Methods

The proliferation of tumour cell lines (T3M4, AsPC-1 and Panc-1) was determined using an MTT assay. Apoptosis was analysed using flow cytometry. Furthermore, p21Cip1/Waf1 and acetylated histone H4 (acH4) expression were confirmed by immunoblot analysis. The in vivo effect of belinostat was studied in a chimeric mouse model. Antitumoural activity was assessed by immunohistochemistry for Ki-67.

Results

Treatment with belinostat resulted in significant in vitro and in vivo growth inhibition of PDAC cells. This was associated with a dose-dependent induction of tumour cell apoptosis. The apoptotic effect of gemcitabine was further enhanced by belinostat. Moreover, treatment with belinostat increased expression of the cell cycle regulator p21Cip1/Waf1 in Panc-1, and of acH4 in all cell lines tested. The reductions in xenograft tumour volumes were associated with inhibition of cell proliferation.

Conclusion

Experimental treatment of human PDAC cells with belinostat is effective in vitro and in vivo and may enhance the efficacy of gemcitabine. A consecutive study of belinostat in pancreatic cancer patients alone, and in combination with gemcitabine, could further clarify these effects in the clinical setting.
Pediatric high-impact conditions in the United States: retrospective analysis of hospitalizations and associated resource use
Authors: Miller Rebecca L , Gebremariam Achamyeleh , Odetola Folafoluwa O
Published: June 2012

Background

Child mortality in the United States has decreased over time, with advance in biomedicine. Little is known about patterns of current pediatric health care delivery for children with the leading causes of child death (high-impact conditions). We described patient and hospital characteristics, and hospital resource use, among children hospitalized with high-impact conditions, according to illness severity.

Methods

We conducted a retrospective study of children 0–18 years of age, hospitalized with discharge diagnoses of the ten leading causes of child death, excluding diagnoses not amenable to hospital care, using the 2006 version of the Kid’s Inpatient Database. National estimates of average and cumulative hospital length of stay and total charges were compared between types of hospitals according to patient illness severity, which was measured using all-patient refined diagnosis related group severity classification into minor-moderate, major, and extreme severity.

Results

There were an estimated 3,084,548 child hospitalizations nationally for high-impact conditions in 2006, distributed evenly among hospital types. Most (84.4%) had minor-moderate illness severity, 12.2% major severity, and 3.4% were extremely ill. Most (64%) of the extremely ill were hospitalized at children’s hospitals. Mean hospital stay was longest among the extremely ill (32.8 days), compared with major (9.8 days, p < 0.0001), or minor-moderate (3.4 days, p < 0.001) illness severity. Mean total hospital charges for the extremely ill were also significantly higher than for hospitalizations with major or minor-moderate severity. Among the extremely ill, more frequent hospitalization at children’s hospitals resulted in higher annual cumulative charges among children’s hospitals ($ 7.4 billion), compared with non-children teaching hospitals ($ 3.2 billion, p = 0.023), and non-children’s non-teaching hospitals ($ 1.5 billion, p < 0.001). Cumulative annual length of hospital stay followed the same pattern, according to hospital type.

Conclusion

Gradation of increasing illness severity among children hospitalized for high-impact conditions was associated with concomitantly increased resource consumption. These findings have significant implications for children’s hospitals which appear to accrue the highest resource use burden due to preferential hospitalization of the most severely ill at these hospitals.
Epidemic spread of ST1-MRSA-IVa in a neonatal intensive care unit, Italy
Authors: Giuffrè Mario , Cipolla Domenico , Bonura Celestino , Geraci Daniela Maria , Aleo Aurora , Di Noto Stefania , Nociforo Federica , Corsello Giovanni , Mammina Caterina
Published: June 2012

Background

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has recently emerged as an important pathogen in neonatal intensive care units (NICUs). The purposes of this study were to characterize methicillin-resistant isolates from an outbreak in a NICU, to examine the genetic traits and clonality of CA-MRSA, and to review the characteristics and outcomes of the neonatal cases and investigate the routes of entry and transmission of the MRSA outbreak strain in the NICU under study.

Methods

The study NICU practiced an active surveillance program for multidrug-resistant organisms, including weekly cultures for detection of MRSA from nasal swabs among all the admitted neonates. All first isolates from surveillance cultures and all clinical isolates were submitted for susceptibility testing and genotyping. Data from each infant’s medical records were prospectively included in a database, and the clinical features and outcomes of the colonized/infected infants were assessed.

Results

A total of 14 infants were colonized or infected by a strain of ST1-MRSA-IVa between April and August 2011. The CA-MRSA strain appeared to have been introduced to the NICU by an infected infant transferred from another hospital. The outbreak was successfully contained by multifaceted infection control interventions.

Conclusions

The results of this study confirm that NICU is a healthcare setting with a critical permeability to CA-MRSA. Active surveillance including molecular typing can help to detect and monitor the spread of antimicrobial drug-resistant organisms, and thus trigger timely control interventions.
Skin cancers among Albinos at a University teaching hospital in Northwestern Tanzania: a retrospective review of 64 cases
Authors: Mabula Joseph B , Chalya Phillipo L , Mchembe Mabula D , Jaka Hyasinta , Giiti Geofrey , Rambau Peter , Masalu Nestory , Kamugisha Erasmus , Robert Ssentongo , Gilyoma Japhet M
Published: June 2012

Background

Skin cancers are a major risk associated with albinism and are thought to be a major cause of death in African albinos. The challenges associated with the care of these patients are numerous and need to be addressed. The aim of this study was to outline the pattern and treatment outcome of skin cancers among albinos treated at our centre and to highlight challenges associated with the care of these patients and proffer solutions for improved outcome.

Methods

This was a retrospective study of all albinos with a histopathological diagnosis of skin cancer seen at Bugando Medical Centre from March 2001 to February 2010. Data collected were analyzed using descriptive statistics.

Results

A total of 64 patients were studied. The male to female ratio was 1.5:1. The median age of patients was 30 years. The median duration of illness at presentation was 24 months. The commonest reason for late presentation was financial problem. Head and the neck was the most frequent site afflicted in 46(71.8%) patients. Squamous cell carcinoma was the most common histopathological type in 75% of cases. Surgical operation was the commonest modality of treatment in 60 (93.8%) patients. Radiotherapy was given in 24(37.5%) patients. Twenty-seven (42.2%) of the patients did not complete their treatment due to lack of funds. Local recurrence following surgical treatment was recorded in 6 (30.0%) patients. Only thirty-seven (61.7%) patients were available for follow-up at 6–12 months and the remaining patients were lost to follow-up.

Conclusions

Skin cancers are the most common cancers among albinos in our environment. Albinism and exposure to ultraviolet light appears to be the most important risk factor in the development of these cancers. Late presentation and failure to complete treatment due to financial difficulties and lack of radiotherapy services at our centre are major challenges in the care of these patients. Early institution of preventive measures, early presentation and treatment, and follow-up should be encouraged in this population for better outcome.
Recombinant sterol esterase from Ophiostoma piceae: an improved biocatalyst expressed in Pichia pastoris
Authors: Barba Cedillo Víctor , Plou Francisco J , Martínez María Jesús
Published: June 2012

Background

The ascomycete Ophiostoma piceae produces a sterol esterase (OPE) with high affinity towards p-nitrophenol, glycerol and sterol esters. Its hydrolytic activity on natural mixtures of triglycerides and sterol esters has been proposed for pitch biocontrol in paper industry since these compounds produce important economic losses during paper pulp manufacture.

Results

Recently, this enzyme has been heterologously expressed in the methylotrophic yeast Pichia pastoris, and the hydrolytic activity of the recombinant protein (OPE*) studied. After the initial screening of different clones expressing the enzyme, only one was selected for showing the highest production rate. Different culture conditions were tested to improve the expression of the recombinant enzyme. Complex media were better than minimal media for production, but in any case the levels of enzymatic activity were higher (7-fold in the best case) than those obtained from O. piceae. The purified enzyme had a molecular mass of 76 kDa, higher than that reported for the native enzyme under SDS-PAGE (60 kDa). Steady-state kinetic characterization of the recombinant protein showed improved catalytic efficiency for this enzyme as compared to the native one, for all the assayed substrates (p-nitrophenol, glycerol, and cholesterol esters). Different causes for this were studied, as the increased glycosylation degree of the recombinant enzyme, their secondary structures or the oxidation of methionine residues. However, none of these could explain the improvements found in the recombinant protein. N-terminal sequencing of OPE* showed that two populations of this enzyme were expressed, having either 6 or 8 amino acid residues more than the native one. This fact affected the aggregation behaviour of the recombinant protein, as was corroborated by analytical ultracentrifugation, thus improving the catalytic efficiency of this enzyme.

Conclusion

P. pastoris resulted to be an optimum biofactory for the heterologous production of recombinant sterol esterase from O. piceae, yielding higher activity levels than those obtained with the saprophytic fungus. The enzyme showed improved kinetic parameters because of its modified N-terminus, which allowed changes in its aggregation behaviour, suggesting that its hydrophobicity has been modified.
High external pH enables more efficient secretion of alkaline α-amylase AmyK38 by Bacillus subtilis
Authors: Manabe Kenji , Kageyama Yasushi , Tohata Masatoshi , Ara Katsutoshi , Ozaki Katsuya , Ogasawara Naotake
Published: June 2012

Background

Bacillus subtilis genome-reduced strain MGB874 exhibits enhanced production of exogenous extracellular alkaline cellulase Egl-237 and subtilisin-like alkaline protease M-protease. Here, we investigated the suitability of strain MGB874 for the production of α-amylase, which was anticipated to provoke secretion stress responses involving the CssRS (Control secretion stress Regulator and Sensor) system.

Results

Compared to wild-type strain 168, the production of a novel alkaline α-amylase, AmyK38, was severely decreased in strain MGB874 and higher secretion stress responses were also induced. Genetic analyses revealed that these phenomena were attributable to the decreased pH of growth medium as a result of the lowered expression of rocG, encoding glutamate dehydrogenase, whose activity leads to NH3 production. Notably, in both the genome-reduced and wild-type strains, an up-shift of the external pH by the addition of an alkaline solution improved AmyK38 production, which was associated with alleviation of the secretion stress response. These results suggest that the optimal external pH for the secretion of AmyK38 is higher than the typical external pH of growth medium used to culture B. subtilis. Under controlled pH conditions, the highest production level (1.08 g l-1) of AmyK38 was obtained using strain MGB874.

Conclusions

We demonstrated for the first time that RocG is an important factor for secretory enzyme production in B. subtilis through its role in preventing acidification of the growth medium. As expected, a higher external pH enabled a more efficient secretion of the alkaline α-amylase AmyK38 in B. subtilis. Under controlled pH conditions, the reduced-genome strain MGB874 was demonstrated to be a beneficial host for the production of AmyK38.
Altered serum levels of IL-33 in patients with advanced systolic chronic heart failure: correlation with oxidative stress
Authors: Zhang Hai-Feng , Xie Shuang-Lun , Chen Yang-Xin , Mai Jing-Ting , Wang Jing-Feng , Zhu Wa-Li , Zhu Li-Guang
Published: June 2012

Background

Interleukin-33 (IL-33) has been linked to chronic heart failure (CHF) in animal studies, but data on serum IL-33 levels in human CHF are not available. We analyzed levels of IL-33 in serum, and investigated the possible role of IL-33 in oxidative stress.

Methods

A total of 191 subjects with advanced systolic CHF (CHF group), 175 patients with pre-existing cardiac diseases but no CHF (non-CHF group), and 177 healthy controls (HC group) were enrolled. Serum levels of IL-33, soluble ST2 (sST2) and N-terminal-pro-brain natriuretic peptide (NT-proBNP), malondialdehyde (MDA) content, erythrocyte superoxide dismutase (eSOD) activity, as well as left ventricular ejection fraction (LVEF), were determined. The exact form of IL-33 in serum was identified. Effects of IL-33 and sST2 on MDA content and SOD activity in angiotensin (Ang II)-stimulated AC16 cells were assessed.

Results

Serum levels of IL-33 and sST2 were elevated in CHF patients, whereas IL-33/sST2 ratios were decreased. In CHF patients, pre-existing cardiac diseases and medications used upon hospital admission did not affect IL-33 concentrations or the IL-33/sST2 ratio. Full-length IL-33, which could not be detected in serum from HC and barely detected in non-CHF patients, was significantly up-regulated in CHF patients. IL-33 levels were positively correlated with markers of CHF severity. IL-33/sST2 ratios were slightly and negatively related to MDA concentrations. IL-33 directly reduced MDA and enhanced SOD activity in Ang II-stimulated AC16 cells, which were greatly attenuated by sST2.

Conclusions

Serum levels of IL-33, especially the full-length form, were elevated in CHF patients whereas IL-33 bioactivity was reduced. In advanced CHF, IL-33 may exert anti-oxidation effects, which may be overwhelmed by concurrently elevated levels of sST2.
Non-volatile memory reduction based on 1-D memory space mapping of a specific set of QC-LDPC codes
Authors: Young Chung-Ping , Chia Chung-Chu , Yang Chao-Chin , Huang Chung-Ming
Published: June 2012

Supporting a great diversity of multi-rate H-matrices for multiple communication protocols requires a large amount of non-volatile memory, which may consume a large silicon area or logic elements and constrain the implementation of an overall decoder. Therefore, schemes for memory reduction are necessary to make the parity-check storage more compact. This study proposes a specific set of quasi-cyclic low-density parity-check (LDPC) (QC-LDPC) codes which can transfer a traditional two-dimensional (2-D) parity-check matrix (H-matrix) into a one-dimensional (1-D) memory space. Compared to the existing schemes, the proposed codes and memory reduction scheme do achieve significant reduction rates. Within a fixed memory space, many more H-matrices for diverse communication protocols can be saved via the proposed QC-LDPC codes, which are well constructed from modified Welch-Costas sequences. Furthermore, relatively good error performances, which outperform computer-generated random LDPC codes and Sridhara-Fuja-Tanner codes, are also shown in our simulation results. Consequently, we conclude that the proposed QC-LDPC codes can enlarge the capacity for saving much more low-BER (bit error rate) H-matrices within a fixed memory space.
Indomethacin protects rats from neuronal damage induced by traumatic brain injury and suppresses hippocampal IL-1β release through the inhibition of Nogo-A expression
Authors: Chao Po-Kuan , Lu Kwok-Tung , Jhu Ji-Yi , Wo Yu-Yuan Peter , Huang Tai-Chun , Ro Long-Sun , Yang Yi-Ling
Published: June 2012

Background

Nogo-A is a member of the reticulon family of membrane-associated proteins and plays an important role in axonal remodeling. The present study aimed to investigate alterations in Nogo-A expression following traumatic brain injury (TBI)-induced inflammation and neuronal damage.

Methods

A weight-drop device was used to deliver a standard traumatic impact to rats. Western blot, RT-PCR and ELISA were used to analyze the expression of Nogo-A and IL-1β. Nogo-A antisense, and an irrelevant control oligonucleotide was intracerebroventricularly infused. We also performed H & E staining and luxol fast blue staining to evaluate the neuronal damage and demyelination resulting from TBI and various treatments.

Results

Based on RT-PCR and western blot analyses, the expression of Nogo-A was found to be significantly upregulated in the hippocampus beginning eight hours after TBI. In addition, TBI caused an apparent elevation in IL-1β levels and severe neuronal damage and demyelination in the tested animals. All of the TBI-associated molecular and cellular consequences could be effectively reversed by treating the animals with the anti-inflammatory drug indomethacin. More importantly, the TBI-associated stimulation in the levels of both Nogo-A and IL-1β could be effectively inhibited by a specific Nogo-A antisense oligonucleotide.

Conclusions

Our findings suggest that the suppression of Nogo-A expression appears to be an early response conferred by indomethacin, which then leads to decreases in the levels of IL-1β and TBI-induced neuron damage.
Monosodium glutamate (MSG) intake is associated with the prevalence of metabolic syndrome in a rural Thai population
Authors: Insawang Tonkla , Selmi Carlo , Cha’on Ubon , Pethlert Supattra , Yongvanit Puangrat , Areejitranusorn Premjai , Boonsiri Patcharee , Khampitak Tueanjit , Tangrassameeprasert Roongpet , Pinitsoontorn Chadamas , Prasongwattana Vitoon , Gershwin M Eric , Hammock Bruce D
Published: June 2012

Background

Epidemiology and animal models suggest that dietary monosodium glutamate (MSG) may contribute to the onset of obesity and the metabolic syndrome.

Methods

Families (n = 324) from a rural area of Thailand were selected and provided MSG as the sole source for the use in meal preparation for 10 days. Three hundred forty-nine subjects aged 35–55 years completed the study and were evaluated for energy and nutrient intake, physical activity, and tobacco smoking. The prevalence of overweight and obesity (BMI ≥ 25 kg/m2), insulin resistance (HOMA-IR >3), and the metabolic syndrome (ATP III criteria) were evaluated according to the daily MSG intake.

Results

The prevalence of the metabolic syndrome was significantly higher in the tertile with the highest MSG intake. Further, every 1 g increase in MSG intake significantly increased the risk of having the metabolic syndrome (odds ratio 1.14, 95% confidence interval-CI- 1.12 - 1.28) or being overweight (odds ratio 1.16, 95% CI 1.04 - 1.29), independent of the total energy intake and the level of physical activity.

Conclusion

Higher amounts of individual MSG consumption are associated with the risk of having the metabolic syndrome and being overweight independent of other major determinants.
Blood volume-monitored regulation of ultrafiltration in fluid-overloaded hemodialysis patients: study protocol for a randomized controlled trial
Authors: Hecking Manfred , Antlanger Marlies , Winnicki Wolfgang , Reiter Thomas , Werzowa Johannes , Haidinger Michael , Weichhart Thomas , Polaschegg Hans-Dietrich , Josten Peter , Exner Isabella , Lorenz-Turnheim Katharina , Eigner Manfred , Paul Gernot , Klauser-Braun Renate , Hörl Walter H , Sunder-Plassmann Gere , Säemann Marcus D
Published: June 2012

Background

Data generated with the body composition monitor (BCM, Fresenius) show, based on bioimpedance technology, that chronic fluid overload in hemodialysis patients is associated with poor survival. However, removing excess fluid by lowering dry weight can be accompanied by intradialytic and postdialytic complications. Here, we aim at testing the hypothesis that, in comparison to conventional hemodialysis, blood volume-monitored regulation of ultrafiltration and dialysate conductivity (UCR) and/or regulation of ultrafiltration and temperature (UTR) will decrease complications when ultrafiltration volumes are systematically increased in fluid-overloaded hemodialysis patients.

Methods/design

BCM measurements yield results on fluid overload (in liters), relative to extracellular water (ECW). In this prospective, multicenter, triple-arm, parallel-group, crossover, randomized, controlled clinical trial, we use BCM measurements, routinely introduced in our three maintenance hemodialysis centers shortly prior to the start of the study, to recruit sixty hemodialysis patients with fluid overload (defined as ≥15% ECW). Patients are randomized 1:1:1 into UCR, UTR and conventional hemodialysis groups. BCM-determined, ‘final’ dry weight is set to normohydration weight −7% of ECW postdialysis, and reached by reducing the previous dry weight, in steps of 0.1 kg per 10 kg body weight, during 12 hemodialysis sessions (one study phase). In case of intradialytic complications, dry weight reduction is decreased, according to a prespecified algorithm. A comparison of intra- and post-dialytic complications among study groups constitutes the primary endpoint. In addition, we will assess relative weight reduction, changes in residual renal function, quality of life measures, and predialysis levels of various laboratory parameters including C-reactive protein, troponin T, and N-terminal pro-B-type natriuretic peptide, before and after the first study phase (secondary outcome parameters).

Discussion

Patients are not requested to revert to their initial degree of fluid overload after each study phase. Therefore, the crossover design of the present study merely serves the purpose of secondary endpoint evaluation, for example to determine patient choice of treatment modality. Previous studies on blood volume monitoring have yielded inconsistent results. Since we include only patients with BCM-determined fluid overload, we expect a benefit for all study participants, due to strict fluid management, which decreases the mortality risk of hemodialysis patients.

Trial registration

ClinicalTrials.gov, NCT01416753
Pulsed electromagnetic fields for the treatment of tibial delayed unions and nonunions. A prospective clinical study and review of the literature
Authors: Assiotis Aggelos , Sachinis Nick P , Chalidis Byron E
Published: June 2012

Background

Pulsed electromagnetic fields (PEMF) stimulation for the treatment of bone nonunion or delayed union have been in use for several years, but on a limited basis. The aim of this study was to assess the overall efficacy of the method in tibial delayed unions and nonunions and identify factors that could affect the final outcome.

Methods

We prospectively reviewed 44 patients (27 men) with a mean age of 49.6 ± 18.4 years that received PEMF therapy due to tibial shaft delayed union or nonunion. In all cases, fracture gap was less than 1 cm and infection or soft tissue defects were absent.

Results

Fracture union was confirmed in 34 cases (77.3%). No relationship was found between union rate and age (p = 0.819), fracture side (left or right) (p = 0.734), fracture type (simple or comminuted, open or closed) (p = 0.111), smoking (p = 0.245), diabetes (p = 0.68) and initial treatment method applied (plates, nail, plaster of paris) (p = 0.395). The time of treatment onset didn’t affect the incidence of fracture healing (p = 0.841). Although statistical significance was not demonstrated, longer treatment duration showed a trend of increased probability of union (p = 0.081).

Conclusion

PEMF stimulation is an effective non-invasive method for addressing non-infected tibial union abnormalities. Its success is not associated with specific fracture or patient related variables and it couldn’t be clearly considered a time-dependent phenomenon.
Normal sulfation levels regulate spinal cord neural precursor cell proliferation and differentiation
Authors: Karus Michael , Samtleben Samira , Busse Claudia , Tsai Teresa , Dietzel Irmgard D , Faissner Andreas , Wiese Stefan
Published: June 2012

Background

Sulfated glycosaminoglycan chains are known for their regulatory functions during neural development and regeneration. However, it is still unknown whether the sulfate residues alone influence, for example, neural precursor cell behavior or whether they act in concert with the sugar backbone. Here, we provide evidence that the unique 473HD-epitope, a representative chondroitin sulfate, is expressed by spinal cord neural precursor cells in vivo and in vitro, suggesting a potential function of sulfated glycosaminoglycans for spinal cord development.

Results

Thus, we applied the widely used sulfation inhibitor sodium chlorate to analyze the importance of normal sulfation levels for spinal cord neural precursor cell biology in vitro. Addition of sodium chlorate to spinal cord neural precursor cell cultures affected cell cycle progression accompanied by changed extracellular signal-regulated kinase 1 or 2 activation levels. This resulted in a higher percentage of neurons already under proliferative conditions. In contrast, the relative number of glial cells was largely unaffected. Strikingly, both morphological and electrophysiological characterization of neural precursor cell-derived neurons demonstrated an attenuated neuronal maturation in the presence of sodium chlorate, including a disturbed neuronal polarization.

Conclusions

In summary, our data suggest that sulfation is an important regulator of both neural precursor cell proliferation and maturation of the neural precursor cell progeny in the developing mouse spinal cord.
Batch correction of microarray data substantially improves the identification of genes differentially expressed in Rheumatoid Arthritis and Osteoarthritis
Authors: Kupfer Peter , Guthke Reinhard , Pohlers Dirk , Huber Rene , Koczan Dirk , Kinne Raimund W
Published: June 2012

Background

Batch effects due to sample preparation or array variation (type, charge, and/or platform) may influence the results of microarray experiments and thus mask and/or confound true biological differences. Of the published approaches for batch correction, the algorithm “Combating Batch Effects When Combining Batches of Gene Expression Microarray Data” (ComBat) appears to be most suitable for small sample sizes and multiple batches.

Methods

Synovial fibroblasts (SFB; purity > 98%) were obtained from rheumatoid arthritis (RA) and osteoarthritis (OA) patients (n = 6 each) and stimulated with TNF-α or TGF-β1 for 0, 1, 2, 4, or 12 hours. Gene expression was analyzed using Affymetrix Human Genome U133 Plus 2.0 chips, an alternative chip definition file, and normalization by Robust Multi-Array Analysis (RMA). Data were batch-corrected for different acquiry dates using ComBat and the efficacy of the correction was validated using hierarchical clustering.

Results

In contrast to the hierarchical clustering dendrogram before batch correction, in which RA and OA patients clustered randomly, batch correction led to a clear separation of RA and OA. Strikingly, this applied not only to the 0 hour time point (i.e., before stimulation with TNF-α/TGF-β1), but also to all time points following stimulation except for the late 12 hour time point. Batch-corrected data then allowed the identification of differentially expressed genes discriminating between RA and OA. Batch correction only marginally modified the original data, as demonstrated by preservation of the main Gene Ontology (GO) categories of interest, and by minimally changed mean expression levels (maximal change 4.087%) or variances for all genes of interest. Eight genes from the GO category “extracellular matrix structural constituent” (5 different collagens, biglycan, and tubulointerstitial nephritis antigen-like 1) were differentially expressed between RA and OA (RA > OA), both constitutively at time point 0, and at all time points following stimulation with either TNF-α or TGF-β1.

Conclusion

Batch correction appears to be an extremely valuable tool to eliminate non-biological batch effects, and allows the identification of genes discriminating between different joint diseases. RA-SFB show an upregulated expression of extracellular matrix components, both constitutively following isolation from the synovial membrane and upon stimulation with disease-relevant cytokines or growth factors, suggesting an “imprinted” alteration of their phenotype.
Visually integrating and exploring high throughput Phenome-Wide Association Study (PheWAS) results using PheWAS-View
Authors: Pendergrass Sarah A , Dudek Scott M , Crawford Dana C , Ritchie Marylyn D
Published: June 2012

Background

Phenome-Wide Association Studies (PheWAS) can be used to investigate the association between single nucleotide polymorphisms (SNPs) and a wide spectrum of phenotypes. This is a complementary approach to Genome Wide Association studies (GWAS) that calculate the association between hundreds of thousands of SNPs and one or a limited range of phenotypes. The extensive exploration of the association between phenotypic structure and genotypic variation through PheWAS produces a set of complex and comprehensive results. Integral to fully inspecting, analysing, and interpreting PheWAS results is visualization of the data.

Results

We have developed the software PheWAS-View for visually integrating PheWAS results, including information about the SNPs, relevant genes, phenotypes, and the interrelationships between phenotypes, that exist in PheWAS. As a result both the fine grain detail as well as the larger trends that exist within PheWAS results can be elucidated.

Conclusions

PheWAS can be used to discover novel relationships between SNPs, phenotypes, and networks of interrelated phenotypes; identify pleiotropy; provide novel mechanistic insights; and foster hypothesis generation – and these results can be both explored and presented with PheWAS-View. PheWAS-View is freely available for non-commercial research institutions, for full details see http://ritchielab.psu.edu/ritchielab/software.
The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines
Authors: Sanvictores Diozele Hazel M , Lucero Marilla G , Nohynek Hanna , Tallo Veronica L , Tanskanen Antti , Nillos Leilani T , Williams Gail ,   and the ARIVAC Consortium
Published: June 2012

Background

A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted.

Results

We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently.

Conclusions

There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff.

Trial registration

Current Controlled Trials ISRCTN62323832
A method for improved clustering and classification of microscopy images using quantitative co-localization coefficients
Authors: Singan Vasanth R , Handzic Kenan , Curran Kathleen M , Simpson Jeremy C
Published: June 2012

Background

The localization of proteins to specific subcellular structures in eukaryotic cells provides important information with respect to their function. Fluorescence microscopy approaches to determine localization distribution have proved to be an essential tool in the characterization of unknown proteins, and are now particularly pertinent as a result of the wide availability of fluorescently-tagged constructs and antibodies. However, there are currently very few image analysis options able to effectively discriminate proteins with apparently similar distributions in cells, despite this information being important for protein characterization.

Findings

We have developed a novel method for combining two existing image analysis approaches, which results in highly efficient and accurate discrimination of proteins with seemingly similar distributions. We have combined image texture-based analysis with quantitative co-localization coefficients, a method that has traditionally only been used to study the spatial overlap between two populations of molecules. Here we describe and present a novel application for quantitative co-localization, as applied to the study of Rab family small GTP binding proteins localizing to the endomembrane system of cultured cells.

Conclusions

We show how quantitative co-localization can be used alongside texture feature analysis, resulting in improved clustering of microscopy images. The use of co-localization as an additional clustering parameter is non-biased and highly applicable to high-throughput image data sets.
Microarray Я US: a user-friendly graphical interface to Bioconductor tools that enables accurate microarray data analysis and expedites comprehensive functional analysis of microarray results
Authors: Dai Yilin , Guo Ling , Li Meng , Chen Yi-Bu
Published: June 2012

Background

Microarray data analysis presents a significant challenge to researchers who are unable to use the powerful Bioconductor and its numerous tools due to their lack of knowledge of R language. Among the few existing software programs that offer a graphic user interface to Bioconductor packages, none have implemented a comprehensive strategy to address the accuracy and reliability issue of microarray data analysis due to the well known probe design problems associated with many widely used microarray chips. There is also a lack of tools that would expedite the functional analysis of microarray results.

Findings

We present Microarray Я US, an R-based graphical user interface that implements over a dozen popular Bioconductor packages to offer researchers a streamlined workflow for routine differential microarray expression data analysis without the need to learn R language. In order to enable a more accurate analysis and interpretation of microarray data, we incorporated the latest custom probe re-definition and re-annotation for Affymetrix and Illumina chips. A versatile microarray results output utility tool was also implemented for easy and fast generation of input files for over 20 of the most widely used functional analysis software programs.

Conclusion

Coupled with a well-designed user interface, Microarray Я US leverages cutting edge Bioconductor packages for researchers with no knowledge in R language. It also enables a more reliable and accurate microarray data analysis and expedites downstream functional analysis of microarray results.
Delivery type not associated with global methylation at birth
Authors: Virani Shama , Dolinoy Dana C , Halubai Sindhu , Jones Tamara R , Domino Steve E , Rozek Laura S , Nahar Muna S , Padmanabhan Vasantha
Published: June 2012

Background

Birth by cesarean delivery (CD) as opposed to vaginal delivery (VD) is associated with altered health outcomes later in life, including respiratory disorders, allergies and risk of developing type I diabetes. Epigenetic gene regulation is a proposed mechanism by which early life exposures affect later health outcomes. Previously, type of delivery has been found to be associated with differences in global methylation levels, but the sample sizes have been small. We measured global methylation in a large birth cohort to identify whether type of delivery is associated with epigenetic changes.

Methods

DNA was isolated from cord blood collected from the University of Michigan Women’s & Children Hospital and bisulfite-converted. The Luminometric Methylation Assay (LUMA) and LINE-1 methylation assay were run on all samples in duplicate.

Results

Global methylation data at CCGG sites throughout the genome, as measured by LUMA, were available from 392 births (52% male; 65% CD), and quantitative methylation levels at LINE-1 repetitive elements were available for 407 births (52% male; 64% CD). LUMA and LINE-1 methylation measurements were negatively correlated in this population (Spearman’s r = −0.13, p =0.01). LUMA measurements were significantly lower for total CD and planned CD, but not emergency CD when compared to VD (median VD = 74.8, median total CD = 74.4, p = 0.03; median planned CD = 74.2, p = 0.02; median emergency CD = 75.3, p = 0.39). However, this association did not persist when adjusting for maternal age, maternal smoking and infant gender. Furthermore, total CD deliveries, planned CD and emergency CD deliveries were not associated with LINE-1 measurements as compared to VD (median VD = 82.2, median total CD = 81.9, p = 0.19; median planned CD = 81.9, p = 0.19; median emergency CD = 82.1, p = 0.52). This lack of association held when adjusting for maternal age, maternal smoking and infant gender in a multivariable model.

Conclusions

Type of delivery was not associated with global methylation in our population, even after adjustment for maternal age, maternal smoking, and infant gender. While type of birth may be associated with later health outcomes, our data suggest that it does not do so through changes in global genomic methylation.