bluuebunny/crossref_metadata_2025 huggingface dataset:
Additional corpus biopsy enhances the detection of Helicobacter pylori infection in a background of gastritis with atrophy
Authors: Lan Hung-Chieh , Chen Tseng-Shing , Li Anna Fen-Yau , Chang Full-Young , Lin Han-Chieh
Published: December 2012

Background

The best sites for biopsy-based tests to evaluateH. pyloriinfection in gastritis with atrophy are not well known. This study aimed to evaluate the site and sensitivity of biopsy-based tests in terms of degree of gastritis with atrophy.

Methods

One hundred and sixty-four (164) uninvestigated dyspepsia patients were enrolled. Biopsy-based tests (i.e., culture, histology Giemsa stain and rapid urease test) and non-invasive tests (anti-H. pyloriIgG) were performed. The gold standard ofH. pyloriinfection was defined according to previous criteria. The sensitivity, specificity, positive predictive rate and negative predictive rate of biopsy-based tests at the gastric antrum and body were calculated in terms of degree of gastritis with atrophy.

Results

The prevalence rate ofH. pyloriinfection in the 164 patients was 63.4%. Gastritis with atrophy was significantly higher at the antrum than at the body (76% vs. 31%;p<0.001). The sensitivity of biopsy-based test decreased when the degree of gastritis with atrophy increased regardless of biopsy site (for normal, mild, moderate, and severe gastritis with atrophy, the sensitivity of histology Giemsa stain was 100%, 100%, 88%, and 66%, respectively, and 100%, 97%, 91%, and 66%, respectively, for rapid urease test). In moderate to severe antrum or body gastritis with atrophy, additional corpus biopsy resulted in increased sensitivity to 16.67% compare to single antrum biopsy.

Conclusions

In moderate to severe gastritis with atrophy, biopsy-based test should include the corpus for avoiding false negative results.
Culture-negative subacute bacterial endocarditis masquerades as granulomatosis with polyangiitis (Wegener’s granulomatosis) involving both the kidney and lung
Authors: Peng Hui , Chen Wen-fang , Wu Chao , Chen Yan-ru , Peng Bo , Paudel Sujay Dutta , Lou Tan-qi
Published: December 2012

Background

Subacute bacterial endocarditis (SBE) occasionally exhibits positive cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) of the anti-proteinase-3 (PR-3) type. Clinically, it mimics ANCA-associated vasculitis, such as Wegener's disease with glomerulonephritis. Lung abscesses are the most common manifestation of lung involvement. We herein report a case of culture-negative SBE strongly c-ANCA/PR3-positive accompanied by pulmonary involvement and glomerulonephritis. In this case, we took biopsies of both the lung and kidney, although renal biopsy is usually preferred over lung biopsy. The lung biopsy showed severe alveolar capillaritis, suggesting vasculitis consistent with polyangiitis. The renal biopsy revealed glomerulonephritis with a membranoproliferative pattern. To our knowledge, this is the first such reported case.

Case presentation

A 68-year-old Chinese male patient presented to our hospital with a fever, cough, chest pain, and recurrent peripheral edema. He had a past medical history significant for treated schistosomiasis 20 years previously. Physical examination revealed palpable purpura, mild hypertension, hepatosplenomegaly, and a holosystolic cardiac murmur (Levine 2/6). Echocardiography showed tricuspid valve vegetations with moderate to severe regurgitation. Serum c-ANCA/PR3 and cryoglobulin were strongly positive. Renal biopsy results indicated membranoproliferative glomerulonephritis with several crescents. Chest CT revealed multiple intraparenchymal and subpleural nodules, and lung biopsy showed polyangiitis. The patient’s ANCA titers, glomerulonephritis, and pulmonary injury all resolved after antibiotic therapy.

Conclusion

SBE may present with positive c-ANCA/PR3, multiple pulmonary nodules, pulmonary polyangiitis, and glomerulonephritis clinically mimicking granulomatosis with polyangiitis (Wegener's granulomatosis).
Signal alterations of the basal ganglia in the differential diagnosis of Parkinson’s disease: a retrospective case-controlled MRI data bank analysis
Authors: Jesse Sarah , Kassubek Jan , Müller Hans-Peter , Ludolph Albert C , Unrath Alexander
Published: December 2012

Background

Based upon the acquainted loss of dopaminergic neurons in the substantia nigra in Parkinson’s disease (PD), we hypothesised changes in magnetic resonance imaging signal intensities of the basal ganglia to be useful as an additional technical tool in the diagnostic work-up.

Methods

Region-of-interest analyses (substantia nigra and globus pallidus internus) of T2-weighted scans were performed in seventy subjects with PD, 170 age- and gender-matched controls and 38 patients with an atypical form of neurodegenerative Parkinsonian syndrome (N = 11 multisystem atrophy, N = 22 progressive supranuclear palsy, N = 5 corticobasal syndrome).

Results

In patients with PD, significant changes in signal intensities within the substantia nigra were observed compared to controls at p < 0.001. For the globus pallidus internus, signal alterations in PD and progressive supranuclear palsy were found to be significant (p < 0.001) if compared to controls. Furthermore, signal changes of substantia nigra correlated with signal intensities of globus pallidus internus in the ipsilateral hemisphere in both groups. Sensitivity was 86% and specificity was 90% for the combined analysis of substantia nigra and globus pallidus internus in the complete patient sample versus controls.

Conclusions

Signal alterations of substantia nigra and globus pallidus internus in routine magnetic resonance imaging were useful to distinguish patients with PD from controls. In addition, signal changes in globus pallidus internus could be used to differentiate progressive supranuclear palsy patients from controls. These analyses have the potential to serve as an additional non-invasive technical tool to support the individual differential diagnosis of PD.
Low level maternal smoking and infant birthweight reduction: genetic contributions of GSTT1 and GSTM1polymorphisms
Authors: Danileviciute Asta , Grazuleviciene Regina , Paulauskas Algimantas , Nadisauskiene Ruta , Nieuwenhuijsen Mark J
Published: December 2012

Background

Genetic susceptibility to tobacco smoke might modify the effect of smoking on pregnancy outcomes.

Methods

We conducted a case–control study of 543 women who delivered singleton live births in Kaunas (Lithuania), examining the association between low-level tobacco smoke exposure (mean: 4.8 cigarettes/day) during pregnancy, GSTT1 and GSTM1 polymorphisms and birthweight of the infant. Multiple linear-regression analysis was performed adjusting for gestational age, maternal education, family status, body mass index, blood pressure, and parity. Subsequently, we tested for the interaction effect of maternal smoking, GSTT1 and GSTM1 genes polymorphisms with birthweight by adding all the product terms in the regression models.

Results

The findings suggested a birthweight reduction among light-smoking with the GSTT1–null genotype (−162.9 g, P = 0.041) and those with the GSTM1–null genotype (−118.7 g, P = 0.069). When a combination of these genotypes was considered, birthweight was significantly lower for infants of smoking women the carriers of the double-null genotypes (−311.2 g, P = 0.008). The interaction effect of maternal smoking, GSTM1 and GSTT1 genotypes was marginally significant on birthweight (−234.5 g, P = 0.078). Among non-smokers, genotype did not independently confer an adverse effect on infant birthweight.

Conclusions

The study shows the GSTT1–null genotype, either presents only one or both with GSTM1–null genotype in a single subject, have a modifying effect on birthweight among smoking women even though their smoking is low level. Our data also indicate that identification of the group of susceptible subjects should be based on both environmental exposure and gene polymorphism. Findings of this study add additional evidence on the interplay among two key GST genes and maternal smoking on birth weight of newborns.
Internalized stigma among patients with schizophrenia in Ethiopia: a cross-sectional facility-based study
Authors: Assefa Dereje , Shibre Teshome , Asher Laura , Fekadu Abebaw
Published: December 2012

Background

Despite the potential impact on treatment adherence and recovery, there is a dearth of data on the extent and correlates of internalized stigma in patients with schizophrenia in low income countries. We conducted a study to determine the extent, domains and correlates of internalized stigma amongst outpatients with schizophrenia in Ethiopia.

Methods

The study was a cross-sectional facility-based survey conducted at a specialist psychiatric hospital in Addis Ababa, Ethiopia. Consecutive consenting individuals with a diagnosis of schizophrenia were recruited and assessed using an Amharic version of the Internalized Stigma of Mental Illness (ISMI) scale.

Results

Data were collected from 212 individuals, who were mostly single (71.2%), unemployed (70.3%) and male (65.1%). Nearly all participants (97.4%) expressed agreement to at least one stigma item contained in the ISMI; 46.7% had a moderate to high mean stigma score. Rural residence (OR = 5.67; 95% CI = 2.30, 13.00; p < 0.001), single marital status (OR = 3.39; 95% CI = 1.40, 8.22; p = 0.019) and having prominent psychotic symptoms (OR = 2.33; 95% CI = 1.17, 4.61; p = 0.016) were associated independently with a higher stigma score. Almost half of those who discontinued their treatment reported that they had done so because of perceived stigma. Those who had attempted suicide (45.3%) were more likely to have a high stigma score (OR = 2.29; 95% CI = 1.27, 4.11; p = 0.006). Over 60% of the variation in the experience of stigma was explained by four factors: social withdrawal (16.7%), perceived discrimination (14.1%), alienation (13.9%) and stereotype endorsement (12.7%).

Conclusion

Internalized stigma is a major problem among persons with schizophrenia in this outpatient setting in Ethiopia. Internalized stigma has the potential to substantially affect adherence to medication and is likely to affect the recovery process.
Risk of death in crashes on Ontario’s highways
Authors: Rzeznikiewiz Damian , Tamim Hala , Macpherson Alison K
Published: December 2012

Background

Motor vehicle collisions (MVCs) that result in one or more fatalities on the 400-series Highways represent a serious public health problem in Ontario, and were estimated to have cost $11 billion in 2004. To date, no studies have examined risk factors for fatal MVCs on Ontario’s 400 series highways.

The investigate how demographic and environmental risk factors are associated with fatal MVCs on Ontario’s 400-Series Highways.

Methods

Data were provided from the Ontario Ministry of Transport database, and included driver demographics, vehicle information, environmental descriptors, structural descriptors, as well as collision information (date and time), and severity of the collision. Multivariate analysis was used to identify factors significantly associated with the odds of dying in a collision.

Results

There were 53,526 vehicles involved in collisions from 2001 to 2006 included in our analysis. Results from the multivariate analysis suggest that collisions with older age and male drivers were associated with an increased risk of involving a fatality. Highway 405 and an undivided 2-way design proved to be the most fatal structural configurations. Collisions in the summer, Fridays, between 12 am-4 am, and in drifting snow conditions during the wintertime were also shown to have a significantly increased risk of fatality.

Conclusion

Our results suggest that interventions to reduce deaths as a result of MVCs should focus on both driver-related and road-related modifications.
Expression profiles of muscle disease-associated genes and their isoforms during differentiation of cultured human skeletal muscle cells
Authors: Abdul-Hussein Saba , van der Ven Peter F M , Tajsharghi Homa
Published: December 2012

Background

The formation of contractile myofibrils requires the stepwise onset of expression of muscle specific proteins. It is likely that elucidation of the expression patterns of muscle-specific sarcomeric proteins is important to understand muscle disorders originating from defects in contractile sarcomeric proteins.

Methods

We investigated the expression profile of a panel of sarcomeric components with a focus on proteins associated with a group of congenital disorders. The analyses were performed in cultured human skeletal muscle cells during myoblast proliferation and myotube development.

Results

Our culture technique resulted in the development of striated myotubes and the expression of adult isoforms of the sarcomeric proteins, such as fast TnI, fast TnT, adult fast and slow MyHC isoforms and predominantly skeletal muscle rather than cardiac actin. Many proteins involved in muscle diseases, such as beta tropomyosin, slow TnI, slow MyBPC and cardiac TnI were readily detected in the initial stages of muscle cell differentiation, suggesting the possibility of an early role for these proteins as constituent of the developing contractile apparatus during myofibrillogenesis. This suggests that in disease conditions the mechanisms of pathogenesis for each of the mutated sarcomeric proteins might be reflected by altered expression patterns, and disturbed assembly of cytoskeletal, myofibrillar structures and muscle development.

Conclusions

In conclusion, we here confirm that cell cultures of human skeletal muscle are an appropriate tool to study developmental stages of myofibrillogenesis. The expression of several disease-associated proteins indicates that they might be a useful model system for studying the pathogenesis of muscle diseases caused by defects in specific sarcomeric constituents.
A case study of the counterpart technical support policy to improve rural health services in Beijing
Authors: Jian Weiyan , Chan Kit Yee , Tang Shunv , Reidpath Daniel D
Published: December 2012

Background

There is, globally, an often observed inequality in the health services available in urban and rural areas. One strategy to overcome the inequality is to require urban doctors to spend time in rural hospitals. This approach was adopted by the Beijing Municipality (population of 20.19 million) to improve rural health services, but the approach has never been systematically evaluated.

Methods

Drawing upon 1.6 million cases from 24 participating hospitals in Beijing (13 urban and 11 rural hospitals) from before and after the implementation of the policy, changes in the rural–urban hospital performance gap were examined. Hospital performance was assessed using changes in six indices over-time: Diagnosis Related Groups quantity, case-mix index (CMI), cost expenditure index (CEI), time expenditure index (TEI), and mortality rates of low- and high-risk diseases.

Results

Significant reductions in rural–urban gaps were observed in DRGs quantity and mortality rates for both high- and low-risk diseases. These results signify improvements of rural hospitals in terms of medical safety, and capacity to treat emergency cases and more diverse illnesses. No changes in the rural–urban gap in CMI were observed. Post-implementation, cost and time efficiencies worsened for the rural hospitals but improved for urban hospitals, leading to a widening rural–urban gap in hospital efficiency.

Conclusions

The strategy for reducing urban–rural gaps in health services adopted, by the Beijing Municipality shows some promise. Gains were not consistent, however, across all performance indicators, and further improvements will need to be tried and evaluated.
Sensory functions in the foot soles in victims of generalized torture, in victims also beaten under the feet (falanga) and in healthy controls – A blinded study using quantitative sensory testing
Authors: Prip Karen , Persson Ann L , Sjölund Bengt H
Published: December 2012

Background

Falanga torture (beatings on the foot soles) produces local chronic pain and severe walking difficulties. We have previously reported signs of neuropathic pain in the feet of falanga victims. The objective here was to clarify underlying pain mechanisms by quantifying sensory impairments in the feet of torture victims who had experienced both generalized torture and those who had been exposed to falanga in addition. An ethnically matched control group was available.

Methods

We employed quantitative sensory testing (QST) by investigators blinded to whether the patients, 32 male torture victims from the Middle East, had (n=15), or had not (n=17) been exposed to falanga. Pain intensity, area and stimulus dependence were used to characterize the pain as were interview data on sensory symptoms. QST included thresholds for touch, cold, warmth, cold-pain, heat-pain, deep pressure pain and wind-up to cutaneous noxious stimuli in the foot soles. Clinical data on anxiety and depression were retrieved.

Results

Almost all falanga victims had moderate or strong pain in their feet and in twice as large an area of their foot soles as other torture victims. One-third of the latter had no pain in their feet and many reported slight pain; in spite of this, there were no differences in foot sole QST data between the tortured groups. A comparison with normal data indicated that both tortured groups had hypoesthesia for all cutaneous sensory fibre groups except those transmitting cold and heat pain, in addition to deep mechano-nociceptive hyperalgesia.

Conclusion

A comparison of the QST data between victims having been exposed to generalized torture and victims who in addition had been exposed to falanga, showed no differences on the group level. The sensory disturbances in relation to our control group are compatible with central sensitization and de-sensitization, pointing to a core role of central mechanisms. A further analysis to create individual sensory profiles from our measurements is in progress.
Efficient one-step production of (S)-1-phenyl-1,2-ethanediol from (R)-enantiomer plus NAD+–NADPH in-situ regeneration using engineered Escherichia coli
Authors: Zhang Rongzhen , Xu Yan , Xiao Rong , Zhang Botao , Wang Lei
Published: December 2012

Background

Candida parapsilosis CCTCC M203011 catalyzes the stereoinversion of (R)-1-phenyl-1,2-ethanediol (PED) through oxidation and reduction. Its NAD+-linked (R)-carbonyl reductase (RCR) catalyzes the oxidization of (R)-PED to 2-hydroxyacetophenone (HAP), and its NADPH-dependent (S)-carbonyl reductase (SCR) catalyzes the reduction of HAP to (S)-PED. The reactions require NAD+ and NADPH as cofactors. However, even if NAD+ and NADPH are added, the biotransformation of (S)-PED from the (R)-enantiomer by an Escherichia coli strain co-expressing RCR and SCR is slow and gives low yields, probably as a result of insufficient or imbalanced redox cofactors. To prepare (S)-PED from the (R)-enantiomer in one-step efficiently, plus redox cofactor regeneration, we introduced pyridine nucleotide transhydrogenases (PNTs) from E. coli to the metabolic pathway of (S)-PED.

Results

The PNTs were successfully introduced into the E. coli strain RSAB. Most of the PNT activities occurred in the cell membrane of E. coli. The introduction of PNTs increased intracellular NAD+ and NADH concentrations and decreased the NADPH pool without affecting the total nucleotide concentration and cell growth properties. The presence of PNTs increased the NADH/NAD+ ratio slightly and reduced the NADPH/NADP+ ratio about two-fold; the ratio of NADPH/NADP+ to NADH/NAD+ was reduced from 36 to 17. So, the PNTs rebalanced the cofactor pathways: the rate of RCR was increased, while the rate of SCR was decreased. When the ratio of NAD+/NADPH was 3.0 or higher, the RSAB strain produced (S)-PED with the highest optical purity, 97.4%, and a yield of 95.2% at 6 h. The introduction of PNTs stimulated increases of 51.5% and 80.6%, respectively, in optical purity and yield, and simultaneously reduced the reaction time seven-fold.

Conclusions

In this work, PNTs were introduced into E. coli to rebalance the cofactor pools within the engineered (S)-PED pathways. The efficient one-step production of (S)-PED plus NAD+–NADPH in-situ regeneration was realized. This work provided new insights into cofactor rebalancing pathways, using metabolic engineering methods, for efficient chiral alcohol production.
Sustainable malaria control: transdisciplinary approaches for translational applications
Authors: Birkholtz Lyn-Marie , Bornman Riana , Focke Walter , Mutero Clifford , de Jager Christiaan
Published: December 2012

With the adoption of the Global Malaria Action Plan, several countries are moving from malaria control towards elimination and eradication. However, the sustainability of some of the approaches taken may be questionable. Here, an overview of malaria control and elimination strategies is provided and the sustainability of each in context of vector- and parasite control is assessed. From this, it can be concluded that transdisciplinary approaches are essential for sustained malaria control and elimination in malaria-endemic communities.
Provider knowledge of treatment policy and dosing regimen with artemether-lumefantrine and quinine in malaria-endemic areas of western Kenya
Authors: Watsierah Carren A , Onyango Rosebella O , Ombaka James H , Abong’o Benard O , Ouma Collins
Published: December 2012

Background

Due to widespread anti-malarial drug resistance in many countries, Kenya included, artemisinin-based Combination Therapy (ACT) has been adopted as the most effective treatment option against malaria. Artemether-lumefantrine (AL) is the first-line ACT for treatment of uncomplicated malaria in Kenya, while quinine is preferred for complicated and severe malaria. Information on the providers’ knowledge and practices prior to or during AL and quinine implementation is scanty. The current study evaluated providers’ knowledge and practices of treatment policy and dosing regimens with AL and quinine in the public, private and not-for-profit drug outlets.

Methods

A cross-sectional survey using three-stage sampling of 288 (126 public, 96 private and 66 not-for-profits) providers in drug outlets was conducted in western Kenya in two Plasmodium falciparum-endemic regions with varying malarial risk. Information on provider in-service training, knowledge (qualification, treatment policy, dosing regimen, recently banned anti-malarials) and on practices (request for written prescription, prescription of AL, selling partial packs and advice given to patients after prescription), was collected.

Results

Only 15.6% of providers in private outlets had received any in-service training on AL use. All (100%) in public and majority (98.4%) in not-for-profit outlets mentioned AL as first line-treatment drug. Quinine was mentioned as second-line drug by 47.9% in private outlets. A total of 92.0% in public, 57.3% in private and 78.8% in not-for-profit outlets stated correct AL dose for adults. A total of 85.7% of providers in public, 30.2% in private and 41.0% in not-for-profit outlets were aware that SP recommendations changed from treatment for mild malaria to IPTp in high risk areas. In-service training influenced treatment regimen for uncomplicated malaria (P = 0.039 and P = 0.039) and severe malaria (P < 0.0001 and P = 0.002) in children and adults, respectively. Most (82.3%) of private outlets sell partial packs of AL while 72.4% do not request for written prescription for AL. In-service training influenced request for written prescription (P = 0.001), AL prescription (P < 0.0001) and selling of partial packs (P < 0.0001).

Conclusion

Public-sector providers have higher knowledge on treatment policy and dosing regimen on recommended anti-malarials. Changes in treatment guidelines should be accompanied by subsequent implementation activities involving all sector players in unbiased strategies.
Wounding, insect chewing and phloem sap feeding differentially alter the leaf proteome of potato, Solanum tuberosum L.
Authors: Duceppe Marc-Olivier , Cloutier Conrad , Michaud Dominique
Published: December 2012

Background

Various factors shape the response of plants to herbivorous insects, including wounding patterns, specific chemical effectors and feeding habits of the attacking herbivore. Here we performed a comparative proteomic analysis of the plant's response to wounding and herbivory, using as a model potato plants (Solanum tuberosum L.) subjected to mechanical wounding, defoliation by the Colorado potato beetle Leptinotarsa decemlineata Say, or phloem sap feeding by the potato aphid Macrosiphum euphorbiae Thomas.

Results

Out of ~500 leaf proteins monitored by two-dimensional gel electrophoresis (2-DE), 31 were up- or downregulated by at least one stress treatment compared to healthy control plants. Of these proteins, 29 were regulated by beetle chewing, 8 by wounding and 8 by aphid feeding. Some proteins were up- or downregulated by two different treatments, while others showed diverging expression patterns in response to different treatments. A number of modulated proteins identified by mass spectrometry were typical defense proteins, including wound-inducible protease inhibitors and pathogenesis-related proteins. Proteins involved in photosynthesis were also modulated, notably by potato beetle feeding inducing a strong decrease of some photosystem I proteins. Quantitative RT PCR assays were performed with nucleotide primers for photosynthesis-related proteins to assess the impact of wounding and herbivory at the gene level. Whereas different, sometimes divergent, responses were observed at the proteome level in response to wounding and potato beetle feeding, downregulating effects were systematically observed for both treatments at the transcriptional level.

Conclusions

These observations illustrate the differential impacts of wounding and insect herbivory on defense- and photosynthesis-related components of the potato leaf proteome, likely associated with the perception of distinct physical and chemical cues in planta.
Proteomic analysis of S-nitrosylation induced by 1-methyl-4-phenylpyridinium (MPP+)
Authors: Komatsubara Akira T , Asano Tomoya , Tsumoto Hiroki , Shimizu Kazuharu , Nishiuchi Takumi , Yoshizumi Masanori , Ozawa Kentaro
Published: December 2012

Background

Nitric oxide (NO) mediates its function through the direct modification of various cellular targets. S-nitrosylation is a post-translational modification of cysteine residues by NO that regulates protein function. Recently, an imbalance of S-nitrosylation has also been linked to neurodegeneration through the impairment of pro-survival proteins by S-nitrosylation.

Results

In the present study, we used two-dimensional gel electrophoresis in conjunction with the modified biotin switch assay for protein S-nitrosothiols using resin-assisted capture (SNO-RAC) to identify proteins that are S-nitrosylated more intensively in neuroblastoma cells treated with a mitochondrial complex I inhibitor, 1-methyl-4-phenylpyridinium (MPP+). We identified 14 proteins for which S-nitrosylation was upregulated and seven proteins for which it was downregulated in MPP+-treated neuroblastoma cells. Immunoblot analysis following SNO-RAC confirmed a large increase in the S-nitrosylation of esterase D (ESD), serine-threonine kinase receptor-associated protein (STRAP) and T-complex protein 1 subunit γ (TCP-1 γ) in MPP+-treated neuroblastoma cells, whereas S-nitrosylation of thioredoxin domain-containing protein 5 precursor (ERp46) was decreased.

Conclusions

These results suggest that S-nitrosylation resulting from mitochondrial dysfunction can compromise neuronal survival through altering multiple signal transduction pathways and might be a potential therapeutic target for neurodegenerative diseases.
Improvement of ovarian response and oocyte quality of aged female by administration of bone morphogenetic protein-6 in a mouse model
Authors: Park Seung S , Park Min J , Joo Bo S , Joo Jong K , Son Jung B , Lee Kyu S
Published: December 2012

Background

Advancing female age remains a difficult problem in infertility treatment. Ovarian angiogenesis plays an important role in follicular development and the activation of ovarian angiogenesis has been emerged as a new strategy for the improvement of age-related decline of oocyte quality. BMP-6 affect gonadotropin signals in granulosa cells and it promotes normal fertility by enabling appropriate response to LH and normal oocyte quality. BMP-6 has a potential role in regulation of angiogenesis and regulates the expression of inhibitor of DNA-binding proteins (Ids). Ids involved in the control and timing of follicle selection and granulosa cells differentiation. Especially, Id-1 is well-characterized target of BMP-6 signaling. Therefore, this study investigated whether co-administration of BMP-6 during superovulation process improves ovarian response, oocyte quality and expression of Id-1 and vascular endothelial growth factor (VEGF) in the ovary of aged female using a mouse model.

Methods

Aged C57BL/6 female mice (26–31 weeks old) were superovulated by injection with 0.1 mL of 5 IU equine chorionic gonadotropin (eCG) containing recombinant mouse BMP-6 at various doses (0, 0.01, 0.1, 1, and 10 ng), followed by injection with 5 IU human chorionic gonadotropin (hCG) 48 h later. Then, the mice were immediately paired with an individual male. The aged control group was superovulated without BMP-6. Young mice of 6–9 weeks old were superovulated without BMP-6 as a positive control for superovulation and in vitro culture of embryos. Eighteen hours after hCG injection, zygotes were retrieved and cultured for 4 days. Both ovaries of each mouse were provided in the examination of ovarian expression of Id-1 and VEGF by reverse transcriptase-polymerase chain reaction, western blot, and immunohistochemistry.

Results

Administration of 0.1 ng BMP-6 significantly increased the number and blastocyst formation rate of oocytes ovulated and ovarian expression of Id-1 and VEGF compared to aged control mice. These increased levels were comparable to those of young control mice.

Conclusions

This result suggests that BMP-6 during ovulation induction plays an important role in improvement of oocyte quality and ovarian response of aged female, possibly by regulating of ovarian Id-1 and VEGF expression.
Development and evaluation of a loop-mediated isothermal amplification assay for the rapid detection of porcine cytomegalovirus under field conditions
Authors: Yang Jin-Long , Zhang Su-Hui , Liu Zuo-Hua , Yang Rui , Huang Yong , Wen Ming
Published: December 2012

Background

Porcine cytomegalovirus (PCMV) induces silent infection in adult pigs but more frequently causes fatal, generalized infection in newborn piglets. This study aimed to develop a new loop-mediated isothermal amplification (LAMP) method for the sensitive, rapid, and inexpensive detection of PCMV under field conditions.

Methods

Tissue obtained from nine-week-old PCMV-free Landrace pigs or pig samples from postmortem examinations were analyzed. The samples were found to have clinical signs and lesions consistent with inclusion body rhinitis. Six specific primers were designed by targeting the PCMV DNA polymerase (DPOL) DNA. The LAMP reaction was optimized in a water bath. The sensitivity and specificity of LAMP and polymerase chain reaction (PCR) were compared.

Results

PCMV DNA was amplified at 65°C, and the result could be detected as early as 30 min into the reaction. Positive reactions could be visualized by the naked eye as a color change brought on by the addition of SYBR Green. The sensitivity and specificity of LAMP were found to be similar to those of the PCR.

Conclusions

LAMP is a high-throughput technique for the detection of PCMV and has a high specificity, sensitivity and simplicity; these factors make it suitable for detection of PCMV under field conditions.
Influenza A virus nucleoprotein derived from Escherichia coli or recombinant vaccinia (Tiantan) virus elicits robust cross-protection in mice
Authors: Huang Baoying , Wang Wenling , Li Renqing , Wang Xiuping , Jiang Tao , Qi Xiangrong , Gao Yingying , Tan Wenjie , Ruan Li
Published: December 2012

Background

Immunity to conserved viral antigens is an attractive approach to develop a universal vaccine against epidemic and pandemic influenza. A nucleoprotein (NP)-based vaccine has been explored and preliminary studies have shown promise. However, no study has explored the immunity and cross-protective efficacy of recombinant NP derived fromEscherichia colicompared with recombinant vaccinia virus (Tiantan).

Methods

Recombinant NP protein (rNP) from influenza virus A/Jingke/30/95(H3N2) was obtained fromE. coliand recombinant vaccinia virus (Tiantan) RVJ1175NP. Purified rNP without adjuvant and RVJ1175NP were used to immunize BALB/c mice intramuscularly. Humoral immune responses were detected by ELISA, while cell-mediated immune responses were measured byex vivoIFN-γ ELISPOT andin vivocytotoxicity assays. The cross-protective efficacy was assessed by a challenge with a heterosubtype of influenza virus A/PR/8/34(H1N1).

Results

Our results demonstrate that a high dose (90 μg) of rNP induced NP-specific antibodies and T cell responses that were comparable with those of RVJ1175NP in mice. Importantly, the survival ratio (36, 73, and 78%) of the vaccinated mice after the influenza virus A/PR/8/34(H1N1) challenge was rNP vaccine dose-dependent (10, 30, and 90 μg, respectively), and no significant differences were observed between the rNP- and RVJ1175NP-immunized (91%) mice.

Conclusions

Influenza A virus NP derived fromE. colior recombinant vaccinia (Tiantan) virus elicited cross-protection against influenza virus in mice, and the immune response and protective efficacy of rNP were comparable to RVJ1175NP. These data provide a basis for the use of prokaryotically expressed NP as a candidate universal influenza vaccine.
Optimization of technology for dietary fiber extraction from Maixiansan by response surface methodology
Authors: Lv Hui-qing , Hu Changfeng , Zhong Hai-ping , Zheng Hong-bin , Wen Chengping
Published: December 2012

Background

Our study aims to determine whether response surface methodology can optimize the extraction of dietary fiber from Maixiansan.

Methods

A Box–Behnken design was employed to optimize the extraction parameters, including α-amylase concentration (X1: 0.3 – 0.5%), enzymolysis time (X
2: 30 – 60 min) and NaOH content (X3: 1.0 – 5.0%), of dietary fiber from Maixiansan using an enzyme–alkali extraction technique.

Results

The optimal technological conditions were as follows: α-amylase concentration: 0.4%; enzymolysis time: 45 min; NaOH content: 4.0%. Under these conditions, the extraction yield reached 57.14%, which was well consistent with the predicted models with a coefficient of determination (R2) of 0.9818. An evaluation of the anti-inflammatory activity indicated that Maixiansan was able to significantly inhibit dextran sodium sulfate-induced ulcerative colitis in rats by increasing the concentration of short-chain fatty acids (acetate, propionate and butyrate), among which the butyrate content was significantly higher in the Maixiansan group than in the other groups.

Conclusion

Our experiments showed that response surface methodology can optimize the extraction of dietary fiber from Maixiansan. Maixiansan could be explored as an anti-ulcerative colitis agent.
Potential impact of a nine-valent vaccine in human papillomavirus related cervical disease
Authors: Serrano Beatriz , Alemany Laia , Tous Sara , Bruni Laia , Clifford Gary M , Weiss Thomas , Bosch Francesc Xavier , de Sanjosé Silvia
Published: December 2012

Background

Information on human papillomavirus (HPV) type distribution is necessary to evaluate the potential impact of current and future HPV vaccines. We estimated the relative contribution (RC) to invasive cervical cancer (ICC) and precancerous cervical lesions of the nine HPV types (HPV 6/11/16/18/31/33/45/52/58) included in an HPV vaccine currently under development.

Methods

Estimations on ICC were based on an international study of 8,977 HPV positive cases and estimations on precancerous cervical lesions were extracted from a published meta-analysis including 115,789 HPV positive women. Globocan 2008 and 2010 World Population Prospects were used to estimate current and future projections of new ICC cases.

Results

RC of the 9 HPV types in ICC was 89.4%, with 18.5% of cases positive for HPV 31/33/45/52/58. Regional variations were observed. RCs varied by histology, ranging between 89.1% in squamous cell carcinomas (SCC) and 95.5% in adenocarcinomas (ADC). HPV 16/18/45 were detected in 94.2% of ADC. RC of the 9 types altogether decreased with age (trend test p < 0.0001), driven by the decrease in older ages of HPV 16/18/45. In contrast, the RC of HPV 31/33/52/58 increased with age. Due to population growth alone, projected estimates of ICC cases attributable to the 9 types are expected to rise from 493,770 new cases in 2012 to 560,887 new cases in 2025.

The RCs of individual high risk HPV types varied by cytological and histological grades of HPV-positive precancerous cervical lesions, and there was an under representation of HPV 18 and 45 compared to ICC.

Conclusions

The addition of HPV 31/33/45/52/58 to HPV types included in current vaccines could prevent almost 90% of ICC cases worldwide. If the nine-valent vaccine achieves the same degree of efficacy than previous vaccines, world incidence rates could be substantially reduced.
Health-related locus of control and health behaviour among university students in North Rhine Westphalia, Germany
Authors: Helmer Stefanie M , Krämer Alexander , Mikolajczyk Rafael T
Published: December 2012

Background

Health control beliefs were postulated to be associated with health behaviour. However, the results of studies assessing these associations suggest that they might not be universal. Among young adults associations have been reported, but the evidence is limited. The objective of this analysis was to re-examine these associations in a sample of university students in Germany.

Findings

Data from a multicentre cross-sectional study among university students in North Rhine-Westphalia, Germany was used (N=3,306). The Multidimensional Health Locus of Control Scale with three dimensions (one internal and two external) and six aspects of health behaviour (smoking habits, alcohol use, drug consumption, being over-/ or underweight, physical activity, and importance of healthy nutrition) were evaluated. Students with stronger internal locus of control paid more attention to healthy nutrition and displayed a higher level of physical activity. Individuals with a stronger belief in health professionals were less likely to use drugs and paid more attention to healthy nutrition. Furthermore, higher scores in the second external locus of control dimension (beliefs in luck or chance) were associated with a higher likelihood of current smoking, lower physical activity and less attention to healthy nutrition.

Conclusions

Students engaged more strongly in unhealthy behaviour if they believed that luck determines health. In contrast, believing in having control over one’s own health was associated with more healthy behaviour. These findings support the need to consider health control beliefs while designing preventive strategies in this specific population.
Patient centred care in diabetology: an Islamic perspective from South Asia
Authors: Niazi Asfandyar K , Kalra Sanjay
Published: December 2012

Patient centred care (PCC) is a healthcare model which is sensitive towards the patients’ preferences, needs and values. Interest in the use of PCC in diabetology has heightened recently. There is a special need of the usage of PCC in Muslim communities. Six out of the ten countries with the highest prevalence of diabetes are Muslim majority countries. There are several religious and sociocultural issues specific to South Asian Muslim societies that merit the need of individualization of care for people with diabetes. Several such issues are presented in this article, along with recommendations for tackling them.
RIDDLE: reflective diffusion and local extension reveal functional associations for unannotated gene sets via proximity in a gene network
Authors: Wang Peggy I , Hwang Sohyun , Kincaid Rodney P , Sullivan Christopher S , Lee Insuk , Marcotte Edward M
Published: December 2012

The growing availability of large-scale functional networks has promoted the development of many successful techniques for predicting functions of genes. Here we extend these network-based principles and techniques to functionally characterize whole sets of genes. We present RIDDLE (Reflective Diffusion and Local Extension), which uses well developed guilt-by-association principles upon a human gene network to identify associations of gene sets. RIDDLE is particularly adept at characterizing sets with no annotations, a major challenge where most traditional set analyses fail. Notably, RIDDLE found microRNA-450a to be strongly implicated in ocular diseases and development. A web application is available at http://www.functionalnet.org/RIDDLE.
Osteoblast Lineage-Specific Effects of Notch Activation in the Skeleton
Authors: Canalis Ernesto , Parker Kristen , Feng Jian Q. , Zanotti Stefano
Published: December 2012

Transgenic overexpression of the Notch1 intracellular domain inhibits osteoblast differentiation and causes osteopenia, and inactivation of Notch1 and Notch2 increases bone volume transiently and induces osteoblastic differentiation. However, the biology of Notch is cell-context-dependent, and consequences of Notch activation in cells of the osteoblastic lineage at various stages of differentiation and in osteocytes have not been defined. For this purpose, RosaNotch mice, where a loxP-flanked STOP cassette placed between the Rosa26 promoter and the NICD coding sequence, were crossed with transgenics expressing the Cre recombinase under the control of the Osterix (Osx), Osteocalcin (Oc), Collagen 1a1 (Col2.3), or Dentin matrix protein1 (Dmp1) promoters. At 1 month, Osx-Cre;RosaNotch and Oc-Cre;RosaNotch mice exhibited osteopenia due to impaired bone formation. In contrast, Col2.3-Cre;RosaNotch and Dmp1-Cre;RosaNotch exhibited increased femoral trabecular bone volume due to a decrease in osteoclast number and eroded surface. In the four lines studied, cortical bone was either not present, was porous, or had the appearance of trabecular bone. Oc-Cre;RosaNotch and Col2.3-Cre;RosaNotch mice exhibited early lethality so that their adult phenotype was not established. At 3 months, Osx-Cre;RosaNotch and Dmp1-Cre;RosaNotch mice displayed increased bone volume, and increased osteoblasts although calcein-demeclocycline labels were diffuse and fragmented, indicating abnormal bone formation. In conclusion, Notch effects in the skeleton are cell-context-dependent. When expressed in immature osteoblasts, Notch arrests their differentiation, causing osteopenia, and when expressed in osteocytes, it causes an initial suppression of bone resorption and increased bone volume, a phenotype that evolves as the mice mature.
Gastrin Induces Sodium-Hydrogen Exchanger 3 Phosphorylation and mTOR Activation via a Phosphoinositide 3-Kinase-/Protein Kinase C-Dependent but AKT-Independent Pathway in Renal Proximal Tubule Cells Derived From a Normotensive Male Human
Authors: Liu Tianbing , Jose Pedro A.
Published: December 2012

Gastrin is natriuretic, but its renal molecular targets and signal transduction pathways are not fully known. In this study, we confirmed the existence of CCKBR (a gastrin receptor) in male human renal proximal tubule cells and discovered that gastrin induced S6 phosphorylation, a downstream component of the phosphatidylinositol 3 kinase (PI3 kinase)-mammalian target of rapamycin pathway. Gastrin also increased the phosphorylation of sodium-hydrogen exchanger 3 (NHE3) at serine 552, caused its internalization, and decreased its expression at the cell surface and NHE activity. The phosphorylation of NHE3 and S6 was dependent on PI3 kinases because it was blocked by 2 different PI3-kinase inhibitors, wortmannin and LY294,002. The phosphorylation of NHE3 and S6 was not affected by the protein kinase A inhibitor H-89 but was blocked by a pan-PKC (chelerythrine) and a conventional PKC (cPKC) inhibitor (Gö6976) (10 μM) and an intracellular calcium chelator, 1,2-bis-(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid, tetra(acetoxymethyl)-ester, suggesting the importance of cPKC and intracellular calcium in the gastrin signaling pathway. The cPKC involved was probably PKCα because it was phosphorylated by gastrin. The gastrin-mediated phosphorylation of NHE3, S6, and PKCα was via phospholipase C because it was blocked by a phospholipase C inhibitor, U73122 (10 μM). The phosphorylation (activation) of AKT, which is usually upstream of mammalian target of rapamycin in the classic PI3 kinase-AKT-p70S6K signaling pathway, was not affected, suggesting that the gastrin-induced phosphorylation of NHE3 and S6 is dependent on both PI3 kinase and PKCα but not AKT.
Evaluation of Markers of Bone Turnover During Lactation in African-Americans: A Comparison With Caucasian Lactation
Authors: Carneiro Raquel M. , Prebehalla Linda , Tedesco Mary Beth , Sereika Susan M. , Gundberg Caren M. , Stewart Andrew F. , Horwitz Mara J.
Published: December 2012

Context:

The African-American skeleton is resistant to PTH; whether it is also resistant to PTHrP and the hormonal milieu of lactation is unknown.

Objectives:

The objective of the study was to assess bone turnover markers in African-Americans during lactation vs Caucasians.

Design and Participants:

A prospective cohort study with repeated measures of markers of bone turnover in 60 African-American women (3 groups of 20: lactating, bottle feeding, and healthy controls), compared with historic Caucasian women.

Setting:

The study was conducted at a university medical center.

Outcome Measures:

Biochemical markers of bone turnover and calcium metabolism were measured.

Results:

25-Hydroxyvitamin D (25-OHD) and PTH were similar among all 3 African-American groups, but 25-OHD was 30%–50% lower and PTH 2-fold higher compared with Caucasians (P < .001, P < .002), with similar 1,25 dihydroxyvitamin D [1,25(OH)2D] values. Formation markers [amino-terminal telopeptide of procollagen-1 (P1NP) and bone-specific alkaline phosphatase (BSAP)] increased significantly (2- to 3-fold) in lactating and bottle-feeding African-American women (P1NP, P < .001; BSAP, P < .001), as did resorption [carboxy-terminal telopeptide of collagen-1 (CTX) and serum amino-terminal telopeptide of collagen 1 (NTX), both P < .001]. P1NP and BSAP were comparable in African-American and Caucasian controls, but CTX and NTX were lower in African-American vs Caucasian controls. African-American lactating mothers displayed quantitatively similar increases in markers of bone formation but slightly lower increases in markers of resorption vs Caucasians (P = .036).

Conclusions:

Despite reported resistance to PTH, lactating African-American women have a significant increase in markers of bone resorption and formation in response the hormonal milieu of lactation. This response is similar to that reported in Caucasian women despite racial differences in 25-OHD and PTH. Whether this is associated with similar bone loss in African-Americans as in Caucasians during lactation is unknown and requires further study.