bluuebunny/crossref_metadata_2025 huggingface dataset:
You Can’t Change What You Don’t See
Authors: Picower Bree
Published: October 2013

Many teachers who enter the profession to “make a difference” do not realize education is a highly political field. This qualitative study examined how teacher education can support new teachers to develop a critical sociopolitical analysis of education. The findings indicate through a year-long course of study, teachers developed two new awarenesses about education. They (1) recognized that everything within education was political and because of this they (2) realized that they had more to learn. The overarching awareness about the political nature of education supported them to recognize four connected insights: (1) certain groups benefit from current structures while (2) others are oppressed, (3) parents and community members should have power in educational decisions that affect them, and (4) race plays a systemic role in all of the above. Within the awareness of realizing they had more to learn, three new stances emerged. Teachers started to (1) reexamine their prior knowledge, (2) realize they needed to hear multiple perspectives before forming opinions, and (3) analyze the political motivation of people providing information. By recognizing that everything is political and by taking a questioning stance, the findings indicate that the teachers reframed their analysis in five key ways. Teachers (1) moved from a focus on individual blame to a focus on systemic inequality; (2) from an ethnocentric perspective to culturally relevant pedagogy; (3) from viewing teachers as holders of power to facilitators who share power; (4) from seeing community deficits to seeing strengths; (5) and from feeling isolated to feeling connected.
Measuring perceptions of shared governance in clinical practice: psychometric testing of the RN-focused Index of Professional Governance (IPNG)
Authors: Lamoureux Julie , Judkins-Cohn Tanya , Butao Rosalina , McCue Victoria , Garcia Fatima
Published: October 2013

Shared governance is considered an innovative management process model that includes shared decision-making between all members of the healthcare workforce and focuses on nurses’ control over their practice and accountability of care. One specific tool that measures shared governance perceptions of nurses is the RN-focused Index of Professional Governance (IPNG). The objective of this study was to assess reliability and add to the validity of the IPNG by further establishing the construct validity and correlating the scale scores to measures of satisfaction obtained from the National Database of Nursing Quality Indicators (or NDNQI) survey. There were 76 respondents representing six units in one hospital. We reported high reliability for each one of the six subscale scores as well as for the total score (Cronbach alphas of 0.94 and higher). Construct validity was supported by the invariance of the scores across age groups along with schooling and experience levels. Concurrent validity was supported by a correlation of the IPNG score with job enjoyment ( r = 0.437, p = 0.002) and the desire to recommend the hospital as a place of employment ( r = 0.442, p = 0.001). The IPNG should also be tested in other healthcare professionals as its scoring ability can compare management, units and departments.
Coping with breathlessness among people with COPD: distinct physiological and behavioural indicators
Authors: Jørgensen Lene Bastrup , Lomborg Kirsten , Dahl Ronald , Pedersen Preben Ulrich
Published: October 2013

Identifying indicators on predominant types of coping with breathlessness may facilitate the possibility for qualified individualised advice on how to live with breathing difficulties. This paper reports the statistical findings on several parameters constituting possible coping-type-specific indicators with the ability to discriminate between four previously identified types of coping with breathlessness. Data were collected from 12 patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in relation to body care during hospital stay and at home. Data consisted of: (a) Bedside forced expiratory volume in 1 s of predicted; (b) scores on the Modified Borg Scale; (c) respiratory rate; (d) peripheral oxygen saturation and (e) use of breaks from activity and break time duration. We found that the following parameters were able to discriminate between the four coping types: COPD severity, intensity of breathlessness, respiratory rate, level of oxygen saturation and the patients’ use of breaks. These findings should be further tested.
The Link between Firm Financial Performance and Investment in Sustainability Initiatives
Authors: Singal Manisha
Published: October 2013

While sustainability initiatives by firms are increasingly encouraged by customers, investors, and the government, the economics of sustainable decisions remains in question. The study described in this paper examines the link between sustainability and economic performance for the hospitality industry, as compared with other businesses. Using data spanning 1991 through 2011 from MSCI’s Environmental, Social, and Governance (ESG) Indices and credit ratings from Standard and Poor’s representing 16,325 firm-years, the analysis finds that hospitality firms on average invest more in environmental programs than do businesses in other industries; that hospitality firms have significantly fewer environmental concerns; that strong financial performance leads to increased investments; and that going green, in turn, pays off in future periods, creating a virtuous cycle. One implication is that hospitality firms should go forward confidently in establishing their sustainability programs, as it appears that customers support the effort financially.
The Woman in Pieces
Authors: Rocha Everardo
Published: October 2013

This article aims to analyze the representation of the feminine identity in advertising. It explores the notion of social identity as a category that is experienced in the tension between classification and value. It also discusses the logic by which ads elaborate an image and, while in this process, transform the woman into a silent and fragmented body. In this article, I follow the anthropological tradition of symbolic systems analysis, and with it contribute to the debate concerning social representations throughout mass communication in general and, particularly, in advertising.
Effect of Zn on the adsorption and desorption of Cry1Ab toxin fromBacillus thuringiensison clay minerals
Authors: Zhou X. Y. , Liu H. F. , Lu X. Z. , Hao J. C. , Shi L. L. , Hu Q.
Published: October 2013

The influence of Zn on the adsorption and desorption of Cry1Ab toxin fromBacillus thuringiensis(Bt) on palygorskite and montmorillonite was studied. The adsorption of the toxin gradually increased with increasing Zn concentration from 0 to 1.0 mmol L–1, and then decreased with further increase in Zn concentration. The adsorption isotherms of the toxin in the absence and presence of Zn were well described by the Langmuir equation (R2> 0.9810–0.9991). The separation factor (RL) decreased with increase of Zn concentration, suggesting that the irreversibility of the adsorption increases. The XRD results showed that the treatment by Tris buffer or Zn(NO3)2solution caused an expansion of the interlayer space of montmorillonite but did not affect palygorskite. The IR spectra suggest that Zn was likely to be combined with amino groups on the surface of the toxin. The presence of Zn during the adsorption of the toxin decreased desorption, suggesting that the residual risk of toxin would be exacerbated if soil is polluted by zinc.
How I treat severe combined immunodeficiency
Authors: Gaspar H. Bobby , Qasim Waseem , Davies E. Graham , Rao Kanchan , Amrolia Persis J. , Veys Paul
Published: October 2013

Severe combined immunodeficiency (SCID) arises from different genetic defects associated with lymphocyte development and function and presents with severe infections. Allogeneic hematopoietic stem cell transplantation is an extremely effective way of restoring immunity in these individuals. Numerous multicenter studies have identified the factors determining successful outcome, and survival for SCID has shown great improvement. Advances in understanding the genetic basis of disease also mean that we increasingly tailor transplant protocols to the specific SCID form. Wherever possible, we attempt to transplant SCID patients without the use of cytoreductive conditioning, but it is clear that this is only successful for specific SCID forms and, although survival is good, in specific patients there are ongoing humoral defects. We aim to use matched related and unrelated donors (including cord blood) whenever possible and have limited the use of mismatched haploidentical donors. The development of autologous hematopoietic stem cell gene therapy provides another treatment of the X-linked and adenosine deaminase–deficient forms of SCID, and we discuss how we have integrated gene therapy into our treatment strategy. These developments together with the advent of universal newborn screening for SCID should allow for a highly favorable outcome for this otherwise lethal condition.
Second-line therapy in elderly patients with advanced nonsmall cell lung cancer
Authors: Quoix Elisabeth , Westeel Virginie , Moreau Lionel , Pichon Eric , Lavolé Armelle , Dauba Jérome , Debieuvre Didier , Souquet Pierre Jean , Bigay-Game Laurence , Dansin Eric , Poudenx Michel , Molinier Olivier , Vaylet Fabien , Moro-Sibilot Denis , Herman Denis , Sennelart Helene , Tredaniel Jean , Mennecier Bertrand , Morin Franck , Baudrin Laurence , Milleron Bernard , Zalcman Gérard
Published: October 2013

There is no dedicated study on second-line treatment for elderly patients with advanced nonsmall cell lung cancer (NSCLC). We report the results on second-line erlotinib therapy from our previously published phase III study comparing single-agent therapy with platinum-based doublet (carboplatin plus paclitaxel) therapy in 451elderly patients.

Erlotinib was given to patients exhibiting disease progression or experiencing excessive toxicity during first-line therapy, until further progression or unacceptable toxicity.

In total, 292 (64.7%) patients received erlotinib as second-line therapy. Initial performance status 0–1, stage IV NSCLC and an Activities of Daily Living score of 6 were independent factors for receiving erlotinib. Median (95% CI) overall survival was 4 (3.2–6.7)versus6.8 (5.0–8.3) months in the single-agent and doublet arms, respectively (p=0.089). Performance status 0–1, never having smoked, adenocarcinoma and weight loss ≤5% were favourable independent prognostic factors of survival, whereas the randomisation arm had no significant impact. Among the 292 patients who received erlotinib, 60 (20.5%) experienced grade 3–4 toxic effects, the most frequent being rash.

Erlotinib as second-line therapy is feasible, leading to efficacy results similar to those obtained in a previous randomised study that was not dedicated to elderly patients, with acceptable toxicity.
Comparative toxicogenomic responses of mercuric and methyl-mercury
Authors: McElwee Matthew K , Ho Lindsey A , Chou Jeff W , Smith Marjolein V , Freedman Jonathan H
Published: October 2013

Background

Mercury is a ubiquitous environmental toxicant that exists in multiple chemical forms. A paucity of information exists regarding the differences or similarities by which different mercurials act at the molecular level.

Results

Transcriptomes of mixed-stage C. elegans following equitoxic sub-, low- and high-toxicity exposures to inorganic mercuric chloride (HgCl2) and organic methylmercury chloride (MeHgCl) were analyzed. In C. elegans, the mercurials had highly different effects on transcription, with MeHgCl affecting the expression of significantly more genes than HgCl2. Bioinformatics analysis indicated that inorganic and organic mercurials affected different biological processes. RNAi identified 18 genes that were important in C. elegans response to mercurial exposure, although only two of these genes responded to both mercurials. To determine if the responses observed in C. elegans were evolutionarily conserved, the two mercurials were investigated in human neuroblastoma (SK-N-SH), hepatocellular carcinoma (HepG2) and embryonic kidney (HEK293) cells. The human homologs of the affected C. elegans genes were then used to test the effects on gene expression and cell viability after using siRNA during HgCl2 and MeHgCl exposure. As was observed with C. elegans, exposure to the HgCl2 and MeHgCl had different effects on gene expression, and different genes were important in the cellular response to the two mercurials.

Conclusions

These results suggest that, contrary to previous reports, inorganic and organic mercurials have different mechanisms of toxicity. The two mercurials induced disparate effects on gene expression, and different genes were important in protecting the organism from mercurial toxicity.
Large-scale polymorphism discovery in macaque G-protein coupled receptors
Authors: Goswami Dharmendra B , Ogawa Lisa M , Ward Joshua M , Miller Gregory M , Vallender Eric J
Published: October 2013

Background

G-protein coupled receptors (GPCRs) play an inordinately large role in human health. Variation in the genes that encode these receptors is associated with numerous disorders across the entire spectrum of disease. GPCRs also represent the single largest class of drug targets and associated pharmacogenetic effects are modulated, in part, by polymorphisms. Recently, non-human primate models have been developed focusing on naturally-occurring, functionally-parallel polymorphisms in candidate genes. This work aims to extend those studies broadly across the roughly 377 non-olfactory GPCRs. Initial efforts include resequencing 44 Indian-origin rhesus macaques (Macaca mulatta), 20 Chinese-origin rhesus macaques, and 32 cynomolgus macaques (M. fascicularis).

Results

Using the Agilent target enrichment system, capture baits were designed for GPCRs off the human and rhesus exonic sequence. Using next generation sequencing technologies, nearly 25,000 SNPs were identified in coding sequences including over 14,000 non-synonymous and more than 9,500 synonymous protein-coding SNPs. As expected, regions showing the least evolutionary constraint show greater rates of polymorphism and greater numbers of higher frequency polymorphisms. While the vast majority of these SNPs are singletons, roughly 1,750 non-synonymous and 2,900 synonymous SNPs were found in multiple individuals.

Conclusions

In all three populations, polymorphism and divergence is highly concentrated in N-terminal and C-terminal domains and the third intracellular loop region of GPCRs, regions critical to ligand-binding and signaling. SNP frequencies in macaques follow a similar pattern of divergence from humans and new polymorphisms in primates have been identified that may parallel those seen in humans, helping to establish better non-human primate models of disease.
Transcriptome analyses of a Chinese hazelnut species Corylus mandshurica
Authors: Ma Hui , Lu Zhiqiang , Liu Bingbing , Qiu Qiang , Liu Jianquan
Published: October 2013

Background

Corylus was renowned for its production of hazelnut and taxol. To understand the local adaptation of Chinese species and speed up breeding efforts in China, we analyzed the leaf transcriptome of Corylus mandshurica, which had a high tolerance to fungal infections and cold.

Results

A total of 12,255,030 clean pair-end reads were generated and then assembled into 37,846 Expressed Sequence Tag (EST) sequences. During functional annotation, 26,565 ESTs were annotated with Gene Ontology (GO) terms using Blast2go and 11,056 ESTs were grouped into the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using KEGG Automatic Annotation Server (KAAS). We identified 45 ESTs that were homologous to enzymes and transcription factors responsible for taxol synthesis. The most differentiated orthologs between C. mandshurica and a European congener, C. avellana, were enriched in stress tolerance to fungal resistance and cold.

Conclusions

In this study, we detected a set of genes related to taxol synthesis in a taxol-producing angiosperm species for the first time and found a close relationship between most differentiated genes and different adaptations to fungal infection and cold in C. mandshurica and C. avellana. These findings provided tools to improve our understanding of local adaptation, genetic breeding and taxol production in hazelnut.
The 7-valent pneumococcal conjugate vaccine elicits cross-functional opsonophagocytic killing responses to Streptococcus pneumoniae serotype 6D in children
Authors: Lee Hyunju , Cha Jung Hwa , Nahm Moon H , Burton Robert L , Kim Kyung-Hyo
Published: October 2013

Background

We investigated the immune response to serogroup 6 with the opsonophagocytic killing assay (OPKA) in children aged 12–23 months of age after immunization with the 7-valent pneumococcal conjugate vaccine (PCV7) containing serotype 6B.

Methods

Blood samples were obtained from 59 children who had blood sampling for medical examination. Immunization status against PCV7 was confirmed by immunization records and samples were categorized according to immunization status into a booster, primary, or control group. The OPKA was performed for serotypes 6A, 6B, 6C, and 6D.

Results

Subjects with no previous PCV7 immunization history showed opsonic activity for serogroup 6 in 5-30% (according to serotype). In subjects vaccinated with a 3-dose primary series, 81% showed opsonic activity for serotypes 6B and 6D, and 29% showed opsonic activity for serotypes 6A and 6C. Among subjects vaccinated with a booster dose, all subjects had opsonic activity against serotype 6B. Subjects in the booster group with opsonic activity against serotypes 6A, 6C, and 6D were 100%, 78%, and 89%, respectively.

Conclusions

In subjects aged 12–23 months, an immune response is elicited after a primary series of immunizations with PCV7 for serotypes 6B and 6D, and a booster dose enhances a cross reactive immune response against serotypes 6A, 6C and 6D.
Self-reported sleep disturbances in renal transplant recipients
Authors: Burkhalter Hanna , Brunner Daniel P , Wirz-Justice Anna , Cajochen Christian , Weaver Terri E , Steiger Jürg , Fehr Thomas , Venzin Reto M , De Geest Sabina
Published: October 2013

Background

Poor sleep quality (SQ) and daytime sleepiness (DS) are common in renal transplant (RTx) recipients; however, related data are rare. This study describes the prevalence and frequency of self-reported sleep disturbances in RTx recipients.

Methods

This cross-sectional study included 249 RTx recipients transplanted at three Swiss transplant centers. All had reported poor SQ and / or DS in a previous study. With the Survey of Sleep (SOS) self-report questionnaire, we screened for sleep and health habits, sleep history, main sleep problems and sleep-related disturbances. To determine a basis for preliminary sleep diagnoses according to the International Classification of Sleep Disorders (ICSD), 164 subjects were interviewed (48 in person, 116 via telephone and 85 refused). Descriptive statistics were used to analyze the data and to determine the frequencies and prevalences of specific sleep disorders.

Results

The sample had a mean age of 59.1 ± 11.6 years (60.2% male); mean time since Tx was 11.1 ± 7.0 years. The most frequent sleep problem was difficulty staying asleep (49.4%), followed by problems falling asleep (32.1%). The most prevalent sleep disturbance was the need to urinate (62.9%), and 27% reported reduced daytime functionality. Interview data showed that most suffered from the first ICSD category: insomnias.

Conclusion

Though often disregarded in RTx recipients, sleep is an essential factor of wellbeing. Our findings show high prevalences and incidences of insomnias, with negative impacts on daytime functionality. This indicates a need for further research on the clinical consequences of sleep disturbances and the benefits of insomnia treatment in RTx recipients.
Quantitative DNA methylation analyses reveal stage dependent DNA methylation and association to clinico-pathological factors in breast tumors
Authors: Klajic Jovana , Fleischer Thomas , Dejeux Emelyne , Edvardsen Hege , Warnberg Fredrik , Bukholm Ida , Lønning Per Eystein , Solvang Hiroko , Børresen-Dale Anne-Lise , Tost Jörg , Kristensen Vessela N
Published: October 2013

Background

Aberrant DNA methylation of regulatory genes has frequently been found in human breast cancers and correlated to clinical outcome. In the present study we investigate stage specific changes in the DNA methylation patterns in order to identify valuable markers to understand how these changes affect breast cancer progression.

Methods

Quantitative DNA methylation analyses of 12 candidate genes ABCB1, BRCCA1, CDKN2A, ESR1, GSTP1, IGF2, MGMT, HMLH1, PPP2R2B, PTEN, RASSF1A and FOXC1 was performed by pyrosequencing a series of 238 breast cancer tissue samples from DCIS to invasive tumors stage I to IV.

Results

Significant differences in methylation levels between the DCIS and invasive stage II tumors were observed for six genes RASSF1A, CDKN2A, MGMT, ABCB1, GSTP1 and FOXC1. RASSF1A, ABCB1 and GSTP1 showed significantly higher methylation levels in late stage compared to the early stage breast carcinoma. Z-score analysis revealed significantly lower methylation levels in DCIS and stage I tumors compared with stage II, III and IV tumors. Methylation levels of PTEN, PPP2R2B, FOXC1, ABCB1 and BRCA1 were lower in tumors harboring TP53 mutations then in tumors with wild type TP53. Z-score analysis showed that TP53 mutated tumors had significantly lower overall methylation levels compared to tumors with wild type TP53. Methylation levels of RASSF1A, PPP2R2B, GSTP1 and FOXC1 were higher in ER positive vs. ER negative tumors and methylation levels of PTEN and CDKN2A were higher in HER2 positive vs. HER2 negative tumors. Z-score analysis also showed that HER2 positive tumors had significantly higher z-scores of methylation compared to the HER2 negative tumors. Univariate survival analysis identifies methylation status of PPP2R2B as significant predictor of overall survival and breast cancer specific survival.

Conclusions

In the present study we report that the level of aberrant DNA methylation is higher in late stage compared with early stage of invasive breast cancers and DCIS for genes mentioned above.
Establishment of the mild, moderate and severe dry eye models using three methods in rabbits
Authors: Li Na , Deng Xinguo , Gao Yang , Zhang Shihua , He Meifeng , Zhao Dongqing
Published: October 2013

Background

Dry eye (DE) is a common eye disease, and appropriate animal models are essential to explore the pathogenesis and therapy of DE. In this study, we aimed to establish rabbit models by three methods.

Methods

In group A, the lacrimal gland, Harderian gland, and nictitating membrane of the left eyes were surgically removed. In group B, the bulbar conjunctiva of the left eyes was burned with 50% trichloroacetic acid. In group C, both methods above were used. The right eyes served as normal controls. The Schirmer I test (SIt), fluorescein staining, and impression cytology were evaluated at baseline and on days 28, 42, and 56.

Results

Both the SIt and goblet cell density were significantly lower in operated eyes compared to the control eyes, while the corneal fluorescein staining scores in the operated eyes were significantly higher than in the control eyes on days 28, 42, and 56 (p< 0.05,p< 0.01 orp< 0.001). The SIt and goblet cell densities in groups B and C were significantly lower than group A on days 28, 42, and 56 (p< 0.05,p< 0.01 orp< 0.001). In addition, the corneal fluorescein staining scores in group C were significantly higher than either group A or group B on days 28, 42, and 56, while fluorescein staining scores were higher in group B than group A on days 42 and 56 days (p< 0.05,p< 0.01 orp< 0.001), with mean score 3.8 ± 1.30 (group A), 7.4 ± 1.14 (group B) and 10.8 ± 1.30 (group C) on day 56.

Conclusions

Results suggest that three separate DE models, with mild, moderate, and severe manifestations of DE, could be stably established, in which conjunctival goblet cells took an important role.
Temporal histological changes in lacrimal and major salivary glands in mouse models of Sjogren’s syndrome
Authors: Xuan Jingxiu , Shen Long , Malyavantham Kishore , Pankewycz Oleh , Ambrus Julian L , Suresh Lakshmanan
Published: October 2013

Background

Evidence in imaging studies suggests that there may be differences in glandular involvement in Sjogren’s syndrome (SS) depending on the stage of the disease. No detailed histological studies are available to show if there are any such difference in glandular involvement at various time periods and stages of SS. This cross sectional study examines the inflammatory changes in mouse models of SS at various ages.

Methods

The histological changes in major salivary and lacrimal glands were studied at ages of 3, 6, 9, 12, 15 and 18 months in both sexes in well characterized mouse models of SS, non-obese diabetes mouse and Interleukin-14 alpha-transgenic mice.

Results

Our results indicate that early inflammation concurrently occur in submandibular and lacrimal glands around the age of 6 weeks. Parotid glands are involved much later in the course of SS with less severe inflammation. Sublingual glands are rarely involved.

Conclusions

Our conclusions are that SS may be an organ specific disease with early inflammation occurring in submandibular and lacrimal glands, followed by the parotid. Non organ specific events occur in later courses of the disease. The understanding of the disease progression is important in tailoring early local therapeutic interventions before complete destruction of salivary and lacrimal glands.
Serum electrolyte levels in relation to macrovascular complications in Chinese patients with diabetes mellitus
Authors: Wang Shenqi , Hou Xuhong , Liu Yu , Lu Huijuan , Wei Li , Bao Yuqian , Jia Weiping
Published: October 2013

Background

The prevalence of diabetes in China is increasing rapidly. However, scarce data are available on serum electrolyte levels in Chinese adults with diabetes, especially in those with cardiovascular complications. This study measured serum electrolyte levels and examined their relationship with macrovascular complications in Chinese adults with diabetes.

Methods

The three gender- and age-matched groups were enrolled into this analysis, which were 1,170 subjects with normal glucose regulation (NGR), 389 with impaired glucose regulation (IGR) and 343 with diabetes. Fasting plasma glucose (FPG), 2-hour post-load plasma glucose (2hPG), glycosylated hemoglobin A1c (HbA1c) and serum electrolyte levels were measured. Data collection included ankle brachial index results.

Results

Serum sodium and magnesium levels in the diabetes group were significantly decreased compared to the NGR group (sodium: 141.0 ± 2.4 vs. 142.1 ± 2.0 mmol/l; magnesium: 0.88 ± 0.08 vs. 0.91 ± 0.07 mmol/l, all P < 0.01), while the serum calcium level was significantly increased (2.36 ± 0.11 vs. 2.33 ± 0.09 mmol/l, P < 0.01). Multiple linear regression showed that serum sodium and magnesium levels in the diabetes group were negatively correlated with FPG, 2hPG and HbA1c (sodium: Std β = −0.35, -0.19, -0.25; magnesium: Std β = −0.29, -0.17, -0.34, all P < 0.01), while the serum calcium level was positively correlated with HbA1c (Std β = 0.17, P < 0.05). In diabetic subjects, serum sodium, magnesium and potassium levels were decreased in the subjects with the elevation of estimated glomerular filtration rates (P < 0.05). ANCOVA analysis suggested that serum magnesium level in subjects with diabetic macrovascular complications was significantly decreased compared with diabetic subjects without macrovascular complications after the effect of some possible confounding being removed (P < 0.05).

Conclusions

Serum sodium and magnesium levels were decreased in Chinese subjects with diabetes, while the observed increase in calcium level correlated with increasing glucose level. Diabetic patients with macrovascular complications had lower serum magnesium level than those with no macrovascular complications.
Transformation of the matrix structure of shrimp shells during bacterial deproteination and demineralization
Authors: Xu Youmei , Bajaj Mini , Schneider Reinhard , Grage Stephan L , Ulrich Anne S , Winter Josef , Gallert Claudia
Published: October 2013

Background

After cellulose and starch, chitin is the third-most abundant biopolymer on earth. Chitin or its deacetylated derivative chitosan is a valuable product with a number of applications. It is one of the main components of shrimp shells, a waste product of the fish industry. To obtain chitin from Penaeus monodon, wet and dried shrimp shells were deproteinated with two specifically enriched proteolytic cultures M1 and M2 and decalcified by in-situ lactic acid forming microorganisms. The viscosity of biologically processed chitin was compared with chemically processed chitin. The former was further investigated for purity, structure and elemental composition by several microscopic techniques and 13C solid state NMR spectroscopy.

Results

About 95% of the protein of wet shrimp shells was removed by proteolytic enrichment culture M2 in 68 h. Subsequent decalcification by lactic acid bacteria (LAB) took 48 h. Deproteination of the same amount of dried shrimps that contained a 3 × higher solid content by the same culture was a little bit faster and was finished after 140 h. The viscosity of chitin was in the order of chemically processed chitin > bioprocessed chitin > commercially available chitin. Results revealed changes in fine structure and chemical composition of the epi-, exo- and endocuticle of chitin from shrimp shells during microbial deproteination and demineralization. From transmission electron microscopy (TEM) overlays and electron energy loss spectroscopy (EELS) analysis, it was found that most protein was present in the exocuticle, whereas most chitin was present in the endocuticle. The calcium content was higher in the endocuticle than in the exocuticle.13C solid state NMR spectra of different chitin confirmed < 3% impurities in the final product.

Conclusions

Bioprocessing of shrimp shell waste resulted in a chitin with high purity. Its viscosity was higher than that of commercially available chitin but lower than that of chemically prepared chitin in our lab. Nevertheless, the biologically processed chitin is a promising alternative for less viscous commercially available chitin. Highly viscous chitin could be generated by our chemical method. Comprehensive structural analyses revealed the distribution of the protein and Ca matrix within the shrimp shell cuticle which might be helpful in developing shrimp waste processing techniques.
Surgical management of hepatocellular carcinoma with tumor thrombi in the inferior vena cava or right atrium
Authors: Wakayama Kenji , Kamiyama Toshiya , Yokoo Hideki , Kakisaka Tatsuhiko , Kamachi Hirofumi , Tsuruga Yosuke , Nakanishi Kazuaki , Shimamura Tsuyoshi , Todo Satoru , Taketomi Akinobu
Published: October 2013

Background

The prognosis for advanced hepatocellular carcinoma (HCC) with tumor thrombi in the inferior vena cava (IVC) or right atrium (RA) is poor, and there is no established effective treatment for this condition. Thus study aimed to evaluate the efficacy of surgical resection and prognosis after surgery for such cases.

Methods

Between January 1990 and December 2012, 891 patients underwent hepatectomy for HCC at our institution. Of these, 13 patients (1.5%) diagnosed with advanced HCC with tumor thrombi in the IVC or RA underwent hepatectomy and thrombectomy. Data detailing the surgical outcome were evaluated and recurrence-free and overall survival rates were calculated using the Kaplan-Meier method.

Results

Seven patients had an IVC thrombus and six had an RA thrombus. Extra-hepatic metastasis was diagnosed in 8 of 13 patients. Surgical procedures included three extended right lobectomies, three extended left lobectomies, five right lobectomies, and two sectionectomies. Right adrenal gland metastases were excised simultaneously in two patients. All IVC thrombi were removed under hepatic vascular exclusion and all RA thrombi were removed under cardiopulmonary bypass (CPB). Four patients (30.8%) experienced controllable postoperative complications, and there was no surgical mortality. The mean postoperative hospital stay for patients with IVC and RA thrombi was 23.6 ± 12.5 days and 21.2 ± 4.6 days, respectively. Curative resection was performed in 5 of 13 cases. The 1- and 3-year overall survival rates were 50.4%, and 21.0%, respectively, and the median survival duration was 15.3 months. The 1- and 3-year overall survival rates for patients who underwent curative surgical resection were 80.0% and 30.0%, respectively, with a median survival duration of 30.8 months. All patients who underwent curative resection developed postoperative recurrences, with a median recurrence-free survival duration of 3.8 months. The 1-year survival rate for patients who underwent noncurative surgery and had residual tumors was 29.2%, with a median survival duration of 10.5 months.

Conclusions

Aggressive surgical resection for HCC with tumor thrombi in the IVC or RA can be performed safely and may improve the prognoses of these patients. However, early recurrence and treatment for recurrent or metastatic tumors remain unresolved issues.
Impact of allergic rhinitis and specific subcutaneous immunotherapy on peripheral blood basophils of patients sensitized to Dermatophagoides pteronyssinus
Authors: Lopes Ana , Azenha Patrícia , Teodósio Cristina , Inácio Maria , Silva Isabel , Loureiro Graça , Martinho António , Luís António S , Trindade Hélder , Pereira Celso , Paiva Artur
Published: October 2013

Background

Basophils are important effectors cells in allergic rhinitis (AR) since they are involved in immunoglobulin (Ig) E – mediated inflammation and in the release of pro-inflammatory mediators. Specific subcutaneous immunotherapy (SCIT) provides clear immunologic modulation in some immune cells, however its systemic effects on basophils are not well known.

Methods

Peripheral blood (PB) samples from 43 patients with allergic rhinitis mono-sensitized to Dermatophagoides pteronyssinus (Dpt) [33 of them under SCIT with allergoid Dpt extract, in maintenance dose (SCIT), with evaluation just before SCIT injection (SCIT-T0) and 4 hours later (SCIT-T4) and the other 10 Dpt allergic patients never having, in the past, undergone specific immunotherapy treatment (NSIT)], and 15 healthy age- and gender-matched controls (HG), were analyzed. For each sample, the total (t-IgE) and specific IgE (s-IgE) was performed, as well as, the relative frequency and absolute number of PB basophils and receptor-bound IgE and IgG expression were evaluated by flow cytometry and the Histamine N-methyltransferase (HNMT) and tryptase α/β1 (TPSAB1) gene expression was assessed by real-time PCR.

Results

Higher levels of receptor-bound IgE were observed in SCIT patients, which are correlated with the levels of serum t-IgE and s-IgE, whereas no significant differences were observed for receptor-bound IgG. Regarding HNMT mRNA expression, significantly lower expression levels were detected in AR patients compared to HG, independently of type of therapy. Moreover a negative correlation was found between HNMT gene expression and time under SCIT. Conversely, tryptase gene expression was significantly up-regulated in NSIT when compared to HG; however in SCIT patients, tryptase gene expression was significantly decreased than in NSIT patients. No differences were found for any parameter between SCIT-T0 and SCIT-T4 with exception of a transient increased expression of tryptase in SCIT-T4.

Conclusion

PB basophils from patients with AR show altered functional features, which seems to be influenced by SCIT, suggesting that these cells could be useful to clarify the SCIT triggered mechanisms at a systemic level.
RETRACTED ARTICLE: DNA barcoding detects contamination and substitution in North American herbal products
Authors: Newmaster Steven G , Grguric Meghan , Shanmughanandhan Dhivya , Ramalingam Sathishkumar , Ragupathy Subramanyam
Published: October 2013

Background

Herbal products available to consumers in the marketplace may be contaminated or substituted with alternative plant species and fillers that are not listed on the labels. According to the World Health Organization, the adulteration of herbal products is a threat to consumer safety. Our research aimed to investigate herbal product integrity and authenticity with the goal of protecting consumers from health risks associated with product substitution and contamination.

Methods

We used DNA barcoding to conduct a blind test of the authenticity for (i) 44 herbal products representing 12 companies and 30 different species of herbs, and (ii) 50 leaf samples collected from 42 herbal species. Our laboratory also assembled the first standard reference material (SRM) herbal barcode library from 100 herbal species of known provenance that were used to identify the unknown herbal products and leaf samples.

Results

We recovered DNA barcodes from most herbal products (91%) and all leaf samples (100%), with 95% species resolution using a tiered approach (rbcL + ITS2). Most (59%) of the products tested contained DNA barcodes from plant species not listed on the labels. Although we were able to authenticate almost half (48%) of the products, one-third of these also contained contaminants and or fillers not listed on the label. Product substitution occurred in 30/44 of the products tested and only 2/12 companies had products without any substitution, contamination or fillers. Some of the contaminants we found pose serious health risks to consumers.

Conclusions

Most of the herbal products tested were of poor quality, including considerable product substitution, contamination and use of fillers. These activities dilute the effectiveness of otherwise useful remedies, lowering the perceived value of all related products because of a lack of consumer confidence in them. We suggest that the herbal industry should embrace DNA barcoding for authenticating herbal products through testing of raw materials used in manufacturing products. The use of an SRM DNA herbal barcode library for testing bulk materials could provide a method for 'best practices’ in the manufacturing of herbal products. This would provide consumers with safe, high quality herbal products.
Effects of early and intensive neuro-rehabilitative treatment on muscle synergies in acute post-stroke patients: a pilot study
Authors: Tropea Peppino , Monaco Vito , Coscia Martina , Posteraro Federico , Micera Silvestro
Published: October 2013

Background

After a stroke, patients show significant modifications of neural control of movement, such as abnormal muscle co-activation, and reduced selectivity and modulation of muscle activity. Nonetheless, results reported in literature do not allow to unequivocally explain whether and, in case, how a cerebrovascular accident affects muscle synergies underlying the control of the upper limb. These discrepancies suggest that a complete understanding of the modular re-organization of muscle activity due to a stroke is still lacking. This pilot study aimed at investigating the effects of the conjunction between the natural ongoing of the pathology and the intense robot-mediated treatment on muscle synergies of the paretic upper limb of subacute post-stroke patients.

Methods

Six subacute patients, homogenous with respect to the age and the time elapsed from the trauma, and ten healthy age-matched subjects were enrolled. The protocol consisted in achieving planar movement of the upper limb while handling the end-effector of a robotic platform. Patients underwent 6 weeks long treatment while clinical scores, kinematics of the end-effector and muscle activity were recorded. Then we verified whether muscle coordination underlying the motor task was significantly affected by the cerebrovascular accident and how muscle synergies were modified along the treatment.

Results

Results show that although muscle synergies in subacute stroke patients were qualitatively comparable to those of healthy subjects, those underlying the movement of the shoulder can reflect the functional deficit induced by the pathology. Moreover, the improvement of motor performance due to the treatment was achieved in conjunction with slight modifications of muscle synergies. In this regard, modifications of muscle synergies appeared to be influenced by the different recovering mechanisms across patients presumably due to the heterogeneity of lesions, sides and location of the accident.

Conclusions

The results support the hypothesis that muscle synergies reflect the injury of the cerebrovascular accident and could document the effects of the functional recovery due to a suitable and customized treatment. Therefore, they open up new possibilities for the development of more effective neuro-rehabilitation protocols.
Electrophysiological characterisation of motor and sensory tracts in patients with hereditary spastic paraplegia (HSP)
Authors: Karle Kathrin N , Schüle Rebecca , Klebe Stephan , Otto Susanne , Frischholz Christian , Liepelt-Scarfone Inga , Schöls Ludger
Published: October 2013

Background

Hereditary spastic paraplegias (HSPs) are characterised by lower limb spasticity due to degeneration of the corticospinal tract. We set out for an electrophysiological characterisation of motor and sensory tracts in patients with HSP.

Methods

We clinically and electrophysiologically examined a cohort of 128 patients with genetically confirmed or clinically probable HSP. Motor evoked potentials (MEPs) to arms and legs, somato-sensory evoked potentials of median and tibial nerves, and nerve conduction studies of tibial, ulnar, sural, and radial nerves were assessed.

Results

Whereas all patients showed clinical signs of spastic paraparesis, MEPs were normal in 27% of patients and revealed a broad spectrum with axonal or demyelinating features in the others. This heterogeneity can at least in part be explained by different underlying genotypes, hinting for distinct pathomechanisms in HSP subtypes. In the largest subgroup, SPG4, an axonal type of damage was evident. Comprehensive electrophysiological testing disclosed a more widespread affection of long fibre tracts involving peripheral nerves and the sensory system in 40%, respectively. Electrophysiological abnormalities correlated with the severity of clinical symptoms.

Conclusions

Whereas HSP is primarily considered as an upper motoneuron disorder, our data suggest a more widespread affection of motor and sensory tracts in the central and peripheral nervous system as a common finding in HSP. The distribution patterns of electrophysiological abnormalities were associated with distinct HSP genotypes and could reflect different underlying pathomechanisms. Electrophysiological measures are independent of symptomatic treatment and may therefore serve as a reliable biomarker in upcoming HSP trials.
Antibacterial mechanisms identified through structural systems pharmacology
Authors: Chang Roger L , Xie Lei , Bourne Philip E , Palsson Bernhard O
Published: October 2013

Background

The growing discipline of structural systems pharmacology is applied prospectively in this study to predict pharmacological outcomes of antibacterial compounds in Escherichia coli K12. This work builds upon previously established methods for structural prediction of ligand binding pockets on protein molecules and utilizes and expands upon the previously developed genome scale model of metabolism integrated with protein structures (GEM-PRO) for E. coli, structurally accounting for protein complexes. Carefully selected case studies are demonstrated to display the potential for this structural systems pharmacology framework in discovery and development of antibacterial compounds.

Results

The prediction framework for antibacterial activity of compounds was validated for a control set of well-studied compounds, recapitulating experimentally-determined protein binding interactions and deleterious growth phenotypes resulting from these interactions. The antibacterial activity of fosfomycin, sulfathiazole, and trimethoprim were accurately predicted, and as a negative control glucose was found to have no predicted antibacterial activity. Previously uncharacterized mechanisms of action were predicted for compounds with known antibacterial properties, including (1-hydroxyheptane-1,1-diyl)bis(phosphonic acid) and cholesteryl oleate. Five candidate inhibitors were predicted for a desirable target protein without any known inhibitors, tryptophan synthase β subunit (TrpB). In addition to the predictions presented, this effort also included significant expansion of the previously developed GEM-PRO to account for physiological assemblies of protein complex structures with activities included in the E. coli K12 metabolic network.

Conclusions

The structural systems pharmacology framework presented in this study was shown to be effective in the prediction of molecular mechanisms of antibacterial compounds. The study provides a promising proof of principle for such an approach to antibacterial development and raises specific molecular and systemic hypotheses about antibacterials that are amenable to experimental testing. This framework, and perhaps also the specific predictions of antibacterials, is extensible to developing antibacterial treatments for pathogenic E. coli and other bacterial pathogens.
HINT1 protein cooperates with cannabinoid 1 receptor to negatively regulate glutamate NMDA receptor activity
Authors: Vicente-Sánchez Ana , Sánchez-Blázquez Pilar , Rodríguez-Muñoz María , Garzón Javier
Published: October 2013

Background

G protein-coupled receptors (GPCRs) are the targets of a large number of drugs currently in therapeutic use. Likewise, the glutamate ionotropic N-methyl-D-aspartate receptor (NMDAR) has been implicated in certain neurological disorders, such as neurodegeration, neuropathic pain and mood disorders, as well as psychosis and schizophrenia. Thus, there is now an important need to characterize the interactions between GPCRs and NMDARs. Indeed, these interactions can produce distinct effects, and whereas the activation of Mu-opioid receptor (MOR) increases the calcium fluxes associated to NMDARs, that of type 1 cannabinoid receptor (CNR1) antagonizes their permeation. Notably, a series of proteins interact with these receptors affecting their responses and interactions, and then emerge as novel therapeutic targets for the aforementioned pathologies.

Results

We found that in the presence of GPCRs, the HINT1 protein influences the activity of NMDARs, whereby NMDAR activation was enhanced in CNR1+/+/HINT1-/- cortical neurons and the cannabinoid agonist WIN55,212-2 provided these cells with no protection against a NMDA insult. NMDAR activity was normalized in these cells by the lentiviral expression of HINT1, which also restored the neuroprotection mediated by cannabinoids. NMDAR activity was also enhanced in CNR1-/-/HINT1+/+ neurons, although this activity was dampened by the expression of GPCRs like the MOR, CNR1 or serotonin 1A (5HT1AR).

Conclusions

The HINT1 protein plays an essential role in the GPCR-NMDAR connection. In the absence of receptor activation, GPCRs collaborate with HINT1 proteins to negatively control NMDAR activity. When activated, most GPCRs release the control of HINT1 and NMDAR responsiveness is enhanced. However, cannabinoids that act through CNR1 maintain the negative control of HINT1 on NMDAR function and their protection against glutamate excitotoxic insult persists.