bluuebunny/crossref_metadata_2025 huggingface dataset:
Engaging the Culture of Death with the Gospel of Life: “Integrating the Catholic Faith in the Practice of Law and medicine”
Authors: Way Robert Michael
Published: October 2013

The lay Catholic, ordained, and religious today are faced with making legal and medical decisions that will affect their health care during a time of incapacity and eventually the final moments of their life. Often times the response to the need for sound legal and medical instructions is met by non-profit, pro-life organizations which provide legal forms such as powers of attorney. By and large, these documents are morally in line with Catholic Church teaching, but do very little for practical application of the law as it interfaces with medicine in the crucible of the emergency room and courtroom. Thus, the “culture of death” which pervades both the professions of law and medicine, and which veils itself in euphemisms such as a “patient's right to die,” creates pragmatic challenges to pre-printed legal documents which may vary from what are statutory in form for individual states. Thus, the promotion of “living wills” is tantamount to the expression of a fear and human desire to escape suffering at all costs. Accordingly, when Catholic physicians are informed of the legal and moral obligations owed to their patients through various estate planning documents, and Catholic lawyers seek to provide an integrated approach to drafting legal documents which include various provisions grounded in Catholic bioethical teaching, documents such as “living wills” and “advanced directives to physicians” ultimately are seen as unnecessary. Thus, engaging the culture of death is best accomplished when both physician and attorney work in their respective fields of practice by discussing the morality of various bioethical decisions with their patients and clients without fear of legal reprisal or recrimination.
Dare to Care for the Elderly: Five Insights
Authors: Callahan A.S.
Published: October 2013

Care is often limited by patient age due to societal forces concerning expense and successful outcome. A mother's critical illness yields insights into care that worked despite advanced age. The five subsequent insights are viewed against data from randomized clinical trials illustrating how we know what we think we know. From this a healthcare model is proposed that insures a healthier elderly population.
Three Reflections upon the Catholic Medical Tradition and Hospice and Palliative Care
Authors: Powers James S.
Published: October 2013

I am often struck at the similarities of caring for older, chronically ill patients, and the long Christian tradition caring for the needy, the poor, and the sick. Particularly when challenged by the scope and size of the task of ministering to this truly underserved population, I find that a spiritual re-focusing provides meaning and comfort. Viewed from the perspective of eternity, end-of-life care occurs in that space between the present and the afterlife. What is the place of spirituality in the care of patients receiving hospice and palliative care? How do Catholic healthcare personnel respond to their patients’ needs? I propose three reflections addressing (1) The Church and human suffering, (2) Catholic framing of goals of care, and (3) Christian stewardship of the cycle of life.
Compassion and Love: The Antidote for Sentimentalism at the End of Life
Authors: Nichols Arland K.
Published: October 2013

The author identifies an increasingly common phenomenon of sentimentalist “pro-lifers” who embrace physician-assisted suicide and euthanasia because sentimental pro-life slogans readily lead to acceptance of these acts. A more principled and rational opposition to various manifestations of the culture of death including assisted suicide and euthanasia is needed. The author proposes that a robust understanding of compassion and love provide an entry point into the discussion that is both rational and emotional. Drawing upon the magisterial teaching of the Church and lived witnesses to that teaching, the essay shows how suffering with the sufferer is the only fitting response to those who suffer at the end of life. A compassionate presence in which caretakers become co-sufferers treats the patient as a subject with great dignity, while euthanasia and assisted suicide treat him as an object to be discarded.
IL-21 signalling via STAT3 primes human naïve B cells to respond to IL-2 to enhance their differentiation into plasmablasts
Authors: Berglund Lucinda J. , Avery Danielle T. , Ma Cindy S. , Moens Leen , Deenick Elissa K. , Bustamante Jacinta , Boisson-Dupuis Stephanie , Wong Melanie , Adelstein Stephen , Arkwright Peter D. , Bacchetta Rosa , Bezrodnik Liliana , Dadi Harjit , Roifman Chaim M. , Fulcher David A. , Ziegler John B. , Smart Joanne M. , Kobayashi Masao , Picard Capucine , Durandy Anne , Cook Matthew C. , Casanova Jean-Laurent , Uzel Gulbu , Tangye Stuart G.
Published: October 2013

Key Points

IL21-mediated induction of CD25 expression on naïve human B cells requires STAT3. A lack of response to IL-2 may amplify humoral immunodeficiency in patients with STAT3, IL2RG, or IL21R mutations due to unresponsiveness to IL21.
Multilocus phylogeny and cryptic diversity in Asian shrew-like moles (Uropsilus, Talpidae): implications for taxonomy and conservation
Authors: Wan Tao , He Kai , Jiang Xue-Long
Published: October 2013

Background

The genusUropsiluscomprises a group of terrestrial, montane mammals endemic to the Hengduan and adjacent mountains. These animals are the most primitive living talpids. The taxonomy has been primarily based on cursory morphological comparisons and the evolutionary affinities are little known. To provide insight into the systematics of this group, we estimated the first multi-locus phylogeny and conducted species delimitation, including taxon sampling throughout their distribution range.

Results

We obtained two mitochondrial genes (~1, 985 bp) and eight nuclear genes (~4, 345 bp) from 56 specimens. Ten distinct evolutionary lineages were recovered from the three recognized species, eight of which were recognized as species/putative species. Five of these putative species were found to be masquerading as the gracile shrew mole. The divergence time estimation results indicated that climate change since the last Miocene and the uplift of the Himalayas may have resulted in the diversification and speciation ofUropsilus.

Conclusions

The cryptic diversity found in this study indicated that the number of species is strongly underestimated under the current taxonomy. Two synonyms ofgracilis(atronatesandnivatus) should be given full species status, and the taxonomic status of another three potential species should be evaluated using extensive taxon sampling, comprehensive morphological, and morphometric approaches. Consequently, the conservation status ofUropsilusspp. should also be re-evaluated, as most of the species/potential species have very limited distribution.
Codon usage patterns in Chinese bayberry (Myrica rubra) based on RNA-Seq data
Authors: Feng Chao , Xu Chang-jie , Wang Yue , Liu Wen-li , Yin Xue-ren , Li Xian , Chen Ming , Chen Kun-song
Published: October 2013

Background

Codon usage analysis has been a classical topic for decades and has significances for studies of evolution, mRNA translation, and new gene discovery, etc. While the codon usage varies among different members of the plant kingdom, indicating the necessity for species-specific study, this work has mostly been limited to model organisms. Recently, the development of deep sequencing, especial RNA-Seq, has made it possible to carry out studies in non-model species.

Result

RNA-Seq data of Chinese bayberry was analyzed to investigate the bias of codon usage and codon pairs. High frequency codons (AGG, GCU, AAG and GAU), as well as low frequency ones (NCG and NUA codons) were identified, and 397 high frequency codon pairs were observed. Meanwhile, 26 preferred and 141 avoided neighboring codon pairs were also identified, which showed more significant bias than the same pairs with one or more intervening codons. Codon patterns were also analyzed at the plant kingdom, organism and gene levels. Changes during plant evolution were evident using RSCU (relative synonymous codon usage), which was even more significant than GC3s (GC content of 3rd synonymous codons). Nine GO categories were differentially and independently influenced by CAI (codon adaptation index) or GC3s, especially in 'Molecular function’ category. Within a gene, the average CAI increased from 0.720 to 0.785 in the first 50 codons, and then more slowly thereafter. Furthermore, the preferred as well as avoided codons at the position just following the start codon AUG were identified and discussed in relation to the key positions in Kozak sequences.

Conclusion

A comprehensive codon usage Table and number of high-frequency codon pairs were established. Bias in codon usage as well as in neighboring codon pairs was observed, and the significance of this in avoiding DNA mutation, increasing protein production and regulating protein synthesis rate was proposed. Codon usage patterns at three levels were revealed and the significance in plant evolution analysis, gene function classification, and protein translation start site predication were discussed. This work promotes the study of codon biology, and provides some reference for analysis and comprehensive application of RNA-Seq data from other non-model species.
Targeted over-expression of endothelin-1 in astrocytes leads to more severe brain damage and vasospasm after subarachnoid hemorrhage
Authors: Yeung Patrick KK , Shen Jiangang , Chung Stephen SM , Chung Sookja K
Published: October 2013

Background

Endothelin-1 (ET-1) is a potent vasoconstrictor, and astrocytic ET-1 is reported to play a role in the pathogenesis of cerebral ischemic injury and cytotoxic edema. However, it is still unknown whether astrocytic ET-1 also contributes to vasogenic edema and vasospasm during subarachnoid hemorrhage (SAH). In the present study, transgenic mice with astrocytic endothelin-1 over-expression (GET-1 mice) were used to investigate the pathophysiological role of ET-1 in SAH pathogenesis.

Results

The GET-1 mice experienced a higher mortality rate and significantly more severe neurological deficits, blood–brain barrier breakdown and vasogenic edema compared to the non-transgenic (Ntg) mice following SAH. Oral administration of vasopressin V1areceptor antagonist, SR 49059, significantly reduced the cerebral water content in the GET-1 mice. Furthermore, the GET-1 mice showed significantly more pronounced middle cerebral arterial (MCA) constriction after SAH. Immunocytochemical analysis showed that the calcium-activated potassium channels and the phospho-eNOS were significantly downregulated, whereas PKC-α expression was significantly upregulated in the MCA of the GET-1 mice when compared to Ntg mice after SAH. Administration of ABT-627 (ETAreceptor antagonist) significantly down-regulated PKC-α expression in the MCA of the GET-1 mice following SAH.

Conclusions

The present study suggests that astrocytic ET-1 involves in SAH-induced cerebral injury, edema and vasospasm, through ETAreceptor and PKC-mediated potassium channel dysfunction. Administration of ABT-627 (ETAreceptor antagonist) and SR 49059 (vasopressin V1areceptor antagonist) resulted in amelioration of edema and vasospasm in mice following SAH. These data provide a strong rationale to investigate SR 49059 and ABT-627 as therapeutic drugs for the treatment of SAH patients.
An international survey of physicians regarding clinical trials: a comparison between Kyoto University Hospital and Seoul National University Hospital
Authors: Ito-Ihara Toshiko , Hong Jeong-Hwa , Kim Ock-Joo , Sumi Eriko , Kim Soo-Youn , Tanaka Shiro , Narita Keiichi , Hatta Taichi , Choi Eun-Kyung , Choi Kyu-Jin , Miyagawa Takuya , Minami Manabu , Murayama Toshinori , Yokode Masayuki
Published: October 2013

Background

International clinical trials are now rapidly expanding into Asia. However, the proportion of global trials is higher in South Korea compared to Japan despite implementation of similar governmental support in both countries. The difference in clinical trial environment might influence the respective physicians’ attitudes and experience towards clinical trials. Therefore, we designed a questionnaire to explore how physicians conceive the issues surrounding clinical trials in both countries.

Methods

A questionnaire survey was conducted at Kyoto University Hospital (KUHP) and Seoul National University Hospital (SNUH) in 2008. The questionnaire consisted of 15 questions and 2 open-ended questions on broad key issues relating to clinical trials.

Results

The number of responders was 301 at KUHP and 398 at SNUH. Doctors with trial experience were 196 at KUHP and 150 at SNUH. Among them, 12% (24/196) at KUHP and 41% (61/150) at SUNH had global trial experience. Most respondents at both institutions viewed clinical trials favorably and thought that conducting clinical trials contributed to medical advances, which would ultimately lead to new and better treatments. The main reason raised as a hindrance to conducting clinical trials was the lack of personnel support and time. Doctors at both university hospitals thought that more clinical research coordinators were required to conduct clinical trials more efficiently. KUHP doctors were driven mainly by pure academic interest or for their desire to find new treatments, while obtaining credits for board certification and co-authorship on manuscripts also served as motivation factors for doctors at SNUH.

Conclusions

Our results revealed that there might be two different approaches to increase clinical trial activity. One is a social level approach to establish clinical trial infrastructure providing sufficient clinical research professionals. The other is an individual level approach that would provide incentives to encourage doctors to participate in and conduct clinical trials.
Phase I drug-interaction study of effects of calcium and magnesium infusions on oxaliplatin pharmacokinetics and acute neurotoxicity in colorectal cancer patients
Authors: Han Catherine H , Khwaounjoo Prashannata , Kilfoyle Dean H , Hill Andrew , McKeage Mark J
Published: October 2013

Background

Calcium and magnesium (Ca/Mg) infusions have been suggested as an effective intervention for preventing oxaliplatin-induced neurotoxicity, but the effects of Ca/Mg infusions on oxaliplatin pharmacokinetics, motor nerve hyperexcitability and acute neurotoxicity symptoms are unclear.

Methods

In this double blind crossover study, colorectal cancer patients undergoing oxaliplatin-based chemotherapy were randomised to receive Ca/Mg (1g Ca Gluconate plus 1g MgSO4) on cycle 1 and placebo (vehicle alone) on cycle 2, or to receive the same treatments in the opposite sequence. Study endpoints included plasma pharmacokinetics of intact oxaliplatin and free platinum; electromyography (EMG) detection of abnormal spontaneous high-frequency motor unit action potential discharges; and patient-reported acute neurotoxicity symptoms and their preferred study treatment for reducing these symptoms.

Results

Nineteen of 20 enrolled patients completed the study. Plasma pharmacokinetics of intact oxaliplatin and free platinum were similar when oxaliplatin was given with Ca/Mg or placebo (ratio of geometric means of AUC0-t with Ca/Mg or placebo: intact oxaliplatin, 0.95 (90% CI, 0.90 – 1.01); free platinum, 0.99 (90% CI, 0.94 – 1.05)). EMG motor nerve hyperexcitability scores were similar with Ca/Mg and placebo (mean difference in EMG score between Ca/Mg and placebo: -0.3 (95% CI, -2.2 – 1.6)). Patient-reported acute neurotoxicity symptoms were similar in frequency with Ca/Mg and placebo. For reducing neurotoxic symptoms, fewer patients preferred Ca/Mg than placebo or neither treatment (26% versus 74%; P<0.01).

Conclusions

Ca/Mg infusions do not alter the clinical pharmacokinetics of oxaliplatin and do not seem to reduce its acute neurotoxicity.

Trial registration

Trial registration identifier ACTRN12611000738921
Structural insights into Resveratrol’s antagonist and partial agonist actions on estrogen receptor alpha
Authors: Chakraborty Sandipan , Levenson Anait S , Biswas Pradip K
Published: October 2013

Background

Resveratrol, a naturally occurring stilbene, has been categorized as a phytoestrogen due to its ability to compete with natural estrogens for binding to estrogen receptor alpha (ERα) and modulate the biological responses exerted by the receptor. Biological effects of resveratrol (RES) on estrogen receptor alpha (ERα) remain highly controversial, since both estrogenic and anti-estrogenic properties were observed.

Results

Here, we provide insight into the structural basis of the agonist/antagonist effects of RES on ERα ligand binding domain (LBD). Using atomistic simulation, we found that RES bound ERα monomer in antagonist conformation, where Helix 12 moves away from the ligand pocket and orients into the co-activator binding groove of LBD, is more stable than RES bound ERα in agonist conformation, where Helix 12 lays over the ligand binding pocket. Upon dimerization, the agonistic conformation of RES-ERα dimer becomes more stable compared to the corresponding monomer but still remains less stable compared to the corresponding dimer in antagonist conformation. Interestingly, while the binding pocket and the binding contacts of RES to ERα are similar to those of pure agonist diethylstilbestrol (DES), the binding energy is much less and the hydrogen bonding contacts also differ providing clues for the partial agonistic character of RES on ERα.

Conclusions

Our Molecular Dynamics simulation of RES-ERα structures with agonist and antagonist orientations of Helix 12 suggests RES action is more similar to Selective Estrogen Receptor Modulator (SERM) opening up the importance of cellular environment and active roles of co-regulator proteins in a given system. Our study reveals that potential co-activators must compete with the Helix 12 and displace it away from the activator binding groove to enhance the agonistic activity.
Possible modulation of FAS and PTP-1B signaling in ameliorative potential of Bombax ceiba against high fat diet induced obesity
Authors: Gupta Paras , Goyal Rohit , Chauhan Yamini , Sharma Pyare Lal
Published: October 2013

Background

Bombax ceiba Linn., commonly called as Semal, is used in various gastro-intestinal disturbances. It contains Lupeol which inhibits PTP-1B, adipogenesis, TG synthesis and accumulation of lipids in adipocytes and adipokines whereas the flavonoids isolated from B. ceiba has FAS inhibitory activity. The present study was aimed to investigate ameliorative potential of Bombax ceiba to experimental obesity in Wistar rats, and its possible mechanism of action.

Methods

Male Wistar albino rats weighing 180-220 g were employed in present study. Experimental obesity was induced by feeding high fat diet for 10 weeks. Methanolic extract of B. ceiba extract 100, 200 and 400 mg/kg and Gemfibrozil 50 mg/kg as standard drug were given orally from 7th to 10th week.

Results

Induction with HFD for 10 weeks caused significant (p < 0.05) increase in % body wt, BMI, LEE indices; serum glucose, triglyceride, LDL, VLDL, cholesterol, free fatty acid, ALT, AST; tissue TBARS, nitrate/nitrite levels; different fat pads and relative liver weight; and significant decrease in food intake (g and kcal), serum HDL and tissue glutathione levels in HFD control rats. Treatment with B. ceiba extract and Gemfibrozil significantly attenuated these HFD induced changes, as compared to HFD control. The effect of B. ceiba 200 and 400 mg/kg was more pronounced in comparison to Gemfibrozil.

Conclusion

On the basis of results obtained, it may be concluded that the methanolic extract of stem bark of Bombax ceiba has significant ameliorative potential against HFD induced obesity in rats, possibly through modulation of FAS and PTP-1B signaling due to the presence of flavonoids and lupeol.
Exendin-4 and sitagliptin protect kidney from ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction
Authors: Chen Yen-Ta , Tsai Tzu-Hsien , Yang Chih-Chau , Sun Cheuk-Kwan , Chang Li-Teh , Chen Hung-Hwa , Chang Chia-Lo , Sung Pei-Hsun , Zhen Yen-Yi , Leu Steve , Chang Hsueh-Wen , Chen Yung-Lung , Yip Hon-Kan
Published: October 2013

Background

This study tested the hypothesis that exendin-4 and sitagliptin can effectively protect kidney from acute ischemia-reperfusion (IR) injury.

Methods

Adult SD-rats (n = 48) equally divided into group 1 (sham control), group 2 (IR injury), group 3 [IR + sitagliptin 600 mg/kg at post-IR 1, 24, 48 hr)], and group 4 [IR + exendin-4 10 μm/kg at 1 hr after procedure] were sacrificed after 24 and 72 hrs (n = 6 at each time from each group) following clamping of bilateral renal pedicles for 60 minutes (groups 2–4).

Results

Serum creatinine level and urine protein to creatinine ratio were highest in group 2 and lowest in group 1 (all p < 0.001) without notable differences between groups 3 and 4. Kidney injury score, expressions of inflammatory biomarkers at mRNA (MMP-9, TNF-α, IL-1β, PAI-1), protein (TNF-α, NF-κB and VCAM-1), and cellular (CD68+) levels in injured kidneys at 24 and 72 hr showed an identical pattern compared to that of creatinine level in all groups (all p < 0.0001). Expressions of oxidized protein, reactive oxygen species (NOX-1, NOX-2), apoptosis (Bax, caspase-3 and PARP), and DNA damage marker (γH2AX+) of IR kidney at 24 and 72 hrs exhibited a pattern similar to that of inflammatory mediators among all groups (all p < 0.01). Renal expression of glucagon-like peptide-1 receptor, and anti-oxidant biomarkers at cellular (GPx, GR) and protein (NQO-1, HO-1, GPx) levels at 24 and 72 hr were lowest in group 1, significantly lower in group 2 than in groups 3 and 4 (all p < 0.01).

Conclusion

Exendin-4 and sitagliptin provided significant protection for the kidneys against acute IR injury.
Efficacy of in-service nutrition training for mid-level providers to improve feeding practices among HIV-positive children in Tanga, Tanzania: study protocol for a cluster randomized controlled trial
Authors: Sunguya Bruno F , Poudel Krishna C , Mlunde Linda B , Urassa David P , Jimba Masamine , Yasuoka Junko
Published: October 2013

Background

Feeding practices and child undernutrition can be improved when trained health workers provide proper nutrition counseling to caregivers. However, this important management component is difficult to achieve in countries where trained health workers are limited; Tanzania is no exception. In rural and semi-urban areas, mid-level providers (MLPs) are left to manage diseases such as HIV/AIDS.

Training health workers in nutrition has been shown to be an effective intervention among HIV-negative children elsewhere, but no studies have been conducted among HIV-positive children. Furthermore, in Tanzania and other countries with MLPs, no evidence currently exists demonstrating an improvement in nutrition among children who receive health services given by MLPs. This study thus aims to examine the efficacy of nutrition training of MLPs on feeding practices and the nutrition status of HIV-positive children in Tanga, Tanzania.

Methods/Design

We will conduct a cluster randomized controlled trial in care and treatment centers (CTCs) in Tanga, Tanzania. The CTCs will be the unit of randomization. We will select 16 CTCs out of 32 for this study, of which we will randomly assign 8 to the intervention arm and 8 to the control arm by coin flipping. From the selected CTCs we will attempt to recruit a total of 800 HIV-positive children aged 6 months to 14 years, half of whom will be receiving care and/or treatment in the CTCs of the intervention arm, and the other half of whom will be receiving care and/or treatment in the CTCs of the control arm (400 children in each condition).

We will provide nutrition training to MLPs of the CTCs selected for the intervention arm. In this intervention, we will use the World Health Organization guidelines on nutrition training of health workers for HIV-positive children aged 6 months to 14 years. The trained MLPs will then provide tailored nutrition counseling to caregivers of children being treated at the 8 CTCs of the intervention arm. We will measure nutrition status and child feeding practices monthly for a total of six months.

Conclusions

Results of this trial will help expanding undernutrition interventions among HIV-positive children in Tanzania and other countries.

Trial registration

Current Controlled Trials:ISRCTN65346364.
Cardiovascular disease risk reduction in rural China: a clustered randomized controlled trial in Zhejiang
Authors: Wei Xiaolin , Zou Guanyang , Gong Weiwei , Yin Jia , Yu Yunxian , Walley John , Zhang Zhitong , King Rebecca , Chen Kun , Chong Marc Ka Chun , Zee Benny Chung Ying , Liu Su , Tang Jinling , Griffiths Sian , Yu Min
Published: October 2013

Background

Cardiovascular disease (CVD) is a major cause of death in China. Despite government efforts, the majority of hypertensive and diabetic patients in China do not receive proper treatment. Reducing CVD events requires long-term care that is proactive, patient-centred, community-based, and sustainable. We have designed a package of interventions for patients at high risk of CVD to be implemented by family doctors based in township hospitals (providers of primary care) in rural Zhejiang, China. This trial aims to determine whether the systematic CVD risk reduction package results in reduced CVD events among patients at risk of CVD compared with usual care, and whether the package is cost-effective and suitable for routine implementation and scale-up.

Methods/Design

This is a prospective, open-label, cluster randomized controlled trial (RCT) with blinded data analysis. The trial will randomize 67 township hospitals with 31,708 participants in three counties in Zhejiang Province. Participants will be identified from existing health records and will comprise adults aged 50 to 74 years, with a calculated 10-year CVD risk of 20% or higher, or diabetes. In the intervention arm, participants will receive a package of interventions including: 1) healthy lifestyle counseling (smoking cessation, and salt, oil, and alcohol reduction); 2) prescription of a combination of drugs (antihypertensives, aspirin, and statin); and 3) adherence support for drug compliance and healthy lifestyle change. In the control arm, participants will receive usual care for hypertension and diabetes management at individual clinicians’ discretion. The primary outcome is the incidence of severe CVD events over 24 months of follow-up. All CVD events will be defined according to the World Health Organization (WHO) monitoring of trends and determinants in cardiovascular disease (MONICA) definitions, diagnosed at the county hospital or higher level, and reported by the Zhejiang surveillance system. Secondary outcomes include: mean systolic and diastolic blood pressure, blood glucose, serum total cholesterol (TC), and adherence to appointments, and drugs and lifestyle changes.

Discussion

This trial focuses on risk reduction of CVD rather than specific diseases. It is not designed to compare therapeutic and healthy lifestyle interventions, but rather their combined effects in primary care settings. Through the trial, we intend to understand the effectiveness of the comprehensive CVD reduction package in routine practice. We also intend to understand the barriers and facilitators to implementing the package, and thus to advise on policy and practice change.

Trial registration

Current Controlled Trials:ISRCTN58988083
Standardization of whole blood immune phenotype monitoring for clinical trials: panels and methods from the ONE study
Authors: Streitz Mathias , Miloud Tewfik , Kapinsky Michael , Reed Michael R , Magari Robert , Geissler Edward K , Hutchinson James A , Vogt Katrin , Schlickeiser Stephan , Kverneland Anders Handrup , Meisel Christian , Volk Hans-Dieter , Sawitzki Birgit
Published: October 2013

Background

Immune monitoring by flow cytometry is a fast and highly informative way of studying the effects of novel therapeutics aimed at reducing transplant rejection or treating autoimmune diseases. The ONE Study consortium has recently initiated a series of clinical trials aimed at using different cell therapies to promote tolerance to renal allografts. To compare the effectiveness of different cell therapies, the consortium developed a robust immune monitoring strategy, including procedures for whole blood (WB) leukocyte subset profiling by flow cytometry.

Methods

Six leukocyte profiling panels computing 7- to 9-surface marker antigens for monitoring the major leukocyte subsets as well as characteristics of T cell, B cell, and dendritic cell (DC) subsets were designed. The precision and variability of these panels were estimated. The assay was standardized within eight international laboratories using Flow-Set Pro beads for mean fluorescence intensity target definition and the flow cytometer setup procedure. Standardization was demonstrated by performing inter-site comparisons.

Results

Optimized methods for sample collection, storage, preparation, and analysis were established, including protocols for gating target subsets. WB specimen age testing demonstrated that staining must be performed within 4 hours of sample collection to keep variability low, meaning less than or equal to 10% for the majority of defined leukocyte subsets. Inter-site comparisons between all participating centers testing shipped normal WB revealed good precision, with a variability of 0.05% to 30% between sites. Intra-assay analyses revealed a variability of 0.05% to 20% for the majority of subpopulations. This was dependent on the frequency of the particular subset, with smaller subsets showing higher variability. The intra-assay variability performance defined limits of quantitation (LoQ) for subsets, which will be the basis for assessing statistically significant differences achieved by the different cell therapies.

Conclusions

Local performance and central analysis of the ONE Study flow cytometry panel yields acceptable variability in a standardized assay at multiple international sites. These panels and procedures with WB allow unmanipulated analysis of changes in absolute cell numbers of leukocyte subsets in single- or multicenter clinical trials. Accordingly, we propose the ONE Study panel may be adopted as a standardized method for monitoring patients in clinical trials enrolling transplant patients, particularly trials of novel tolerance promoting therapies, to facilitate fair and meaningful comparisons between trials.
Aldehyde dehydrogenase and ATP binding cassette transporter G2 (ABCG2) functional assays isolate different populations of prostate stem cells where ABCG2 function selects for cells with increased stem cell activity
Authors: Gangavarapu Kalyan J , Azabdaftari Gissou , Morrison Carl D , Miller Austin , Foster Barbara A , Huss Wendy J
Published: October 2013

Introduction

High expression of aldehyde dehydrogenase1A1 (ALDH1A1) is observed in many organs and tumors and may identify benign and cancer stem cell populations.

Methods

In the current study, the stem cell characteristics were determined in cells isolated from human prostate cell lines and clinical prostate specimens based upon the ALDEFLUOR™ assay. Cells isolated based on the ALDEFLUOR™ assay were compared to cells isolated based on ATP binding cassette transporter G2 (ABCG2) activity using the side population assay. To test for stem cell characteristics of self-renewal and multipotency, cells with high and low ALDH1A1 activity, based on the ALDEFLUOR™ assay (ALDHHi and ALDHLow), were isolated from prostate clinical specimens and were recombined with rat urogenital sinus mesenchyme to induce prostate gland formation.

Results

The percentage of ALDHHi cells in prostate cell lines (RWPE-1, RWPE-2, CWR-R1, and DU-145) was 0.5 to 6%, similarly in non-tumor and tumor clinical specimens the percentage of ALDHHi cells was 0.6 to 4%. Recombinants using ALDHHi cells serially generated prostate tissue up to three generations with as few as 250 starting cells. Immunohistochemical analysis of the recombinants using ALDHHi cells contained prostatic glands frequently expressing androgen receptor (AR), p63, chromogranin A, ALDH1A1, ABCG2, and prostate specific antigen (PSA), compared to their ALDHLow counterparts. Inhibition of ALDH resulted in the reduction of sphere formation capabilities in the CWR-R1, but not in the RWPE-2 and DU-145, prostate cell lines. ABCG2 inhibition resulted in a more robust decrease of sphere formation in androgen sensitive cell lines, CWR-R1 and RWPE-2, but not androgen insensitive DU-145. ALDH1A1 expression was enriched in ALDHHi cells and non-side population cells. ABCG2 expression was only enriched in side population cells.

Conclusions

The percentage of ALDHHi cells in prostate cell lines and prostate tissue was consistently higher compared to cells with high ABCG2 activity, identified with the side population assay. The expression of the stem and differentiation markers indicates the ALDHHi recombinants contained cells with self-renewal and multipotency activity. When the two assays were directly compared, cells with the side population phenotype demonstrated more stem cell potential in the tissue recombination assay compared to ALDHHi cells. The increased stem cell potential of side population cells in the tissue recombination assay and the decrease in sphere formation when ABCG2 is inhibited indicates that the side population enriches for prostate stem cells.
Structural and thermodynamic signatures that define pseudotriloop RNA hairpins
Authors: van der Werf Ramon , Wijmenga Sybren S. , Heus Hans A. , Olsthoorn René C.L.
Published: October 2013

Pseudotriloop (PTL) structures in RNAs have been recognized as essential elements in RNA folding and recognition of proteins. PTL structures are derived from hexaloops by formation of a cross–loop base pair leaving a triloop and 3′ bulged out residue. Despite their common presence and functional importance, insufficient structural and thermodynamic data are available that can be used to predict formation of PTLs from sequence alone. Using NMR spectroscopy and UV-melting data we established factors that contribute to the formation and stability of PTL structures derived from hepatitis B virus and human foamy virus. The NMR data show that, besides the cross–loop base pair, also a 3′ pyrimidine bulge and a G–C loop-closing base pair are primary determinants of PTL formation. By changing the G–C closing base pair into C–G, the PTL switches into a hexaloop. Comparison of these rules with regular triloop hairpins and PTLs from other sources is discussed as well as the conservation of a PTL in human foamy virus and other spumaretroviruses.
Back to the role of global English in European education
Authors: Воевода  , Voevoda Elena
Published: October 2013

The article considers the status of English as a global means of communication in the light of modern approaches to the development of language teaching and studies the motives for learning the language in European countries. The author analyses the attempts to develop simplified variants of English the possibility of using them in the classroom. She concludes that neither Globish, nor the variant of English devoid of the cultural component can be used in the classroom either at school or at university. The author further underlined that English does not act as a dominant language in Europe and it does not oust other languages, but is widely used as an auxiliary means of communication.
Learning Preferences Under Noise and Loss Aversion: An Optimization Approach
Authors: Bertsimas Dimitris , O'Hair Allison
Published: October 2013

Preference learning has been a topic of research in many fields, including operations research, marketing, machine learning, and behavioral economics. In this work, we strive to combine the ideas from these different fields into a single methodology to learn preferences and make decisions. We use robust and integer optimization in an adaptive and dynamic way to determine preferences from data that are consistent with human behavior. We use integer optimization to address human inconsistency, robust optimization and conditional value at risk (CVaR) to address loss aversion, and adaptive conjoint analysis and linear optimization to frame the questions to learn preferences. The paper makes the following methodological contributions: to the robust optimization literature by proposing a method to derive uncertainty sets from adaptive questionnaires, to the marketing literature by using the analytic center of discrete sets (as opposed to polyhedra) to capture errors and inconsistencies, and to the risk modeling literature by using efficient methods from computer science for sampling to optimize CVaR. We have implemented an online software that uses the proposed approach and report empirical evidence of its strength.
Foci of enterobiasis and ascariasis in the Świętokrzyskie Province in 2005-2009
Authors: Bartosik Katarzyna , Lachowska-Kotowska Patrycja , Kulisz Joanna , Grzęda Karol , Szymańska Jolanta , Buczek Alicja
Published: October 2013

Cosmopolitical pinworm (Enterobius vermicularis) and human ascaris (Ascaris lumbricoides) are the most often nematode parasitising in human gastrointestinal tract all over the world. Pinworm are more common in temperate climatic zones of developed countries of Europe and the United States, whereas human ascaris is the most often in developing countries of Central and South America, Africa and Asia. Taking into account the widespread occurrence of enterobiasis and ascariasis and their impact on human health, it is necessary to monitor the incidence of these infestations all over the world. The aim of our work was to present the incidence of parasitic diseases caused by Enterobius vermicularis and Ascaris lumbricoides in Central Poland in the years 2005-2009. The research was conducted in Świętokrzyskie Region, which is an agricultural region of Central Poland. The data concerning the incidence of enterobiasis and ascariasis were collected from Provincial Sanitary-Epidemiological Station in Kielce. Foci of parasitic invasion covered only these cases, when at least two people were affected at the same time and the same place. Taking into account the number and localization of foci of enterobiasis and ascariasis as well as socioeconomic data from Central Statistical Office in Kielce, epidemiologic analysis of parasitic infections in Świętokrzyskie Region was done. In the years 2005-2009 in Świętokrzyskie Region 21 foci of enterobiasis and 16 foci of ascariasis were registered. The most cases of enterobiasis were registered in the year 2005 (12 foci). In examined period, the highest number of ascariasis was noted in 2008 (4 house foci and 2 school foci). The high incidence of parasitic infections of digestive tract in Świętokrzyskie Region is a consequence of several fac tors – most of inhabitants are professionally connected with agricultural and forest environment, what makes higher the risk of soil-transmitted helminthiasis. Moreover, it can be also connected with low sanitary conditions and the lack of appropriate environmental security against soil and water contamination with feces.
Effects of various naturally occurring compounds (arbutin, borneol, esculetin, esculin, ellagic acid, gallic acid, hesperidine, piperitol, piperonal, quercetin, thymoquinone and ursolic acid) against maximal electroshock-induced seizures in mice
Authors: Łuszczki Jarogniew J , Włodarczyk Maciej , Gleńsk Michał , Marzęda Ewa , Durmowicz Dariusz , Florek-Łuszczki Magdalena
Published: October 2013

The aim of this study was to perform the anticonvulsant screening test to select some naturally occurring substances isolated from herbs and medicinal plants that could offer a distinct protection against maximal electroshock (MES)-induced tonic seizures in mice. The screening test was performed for 12 substances (i.e., arbutin, borneol, esculetin, esculin, ellagic acid, gallic acid, hesperidine, piperitol, piperonal, quercetin, thymoquinone and ursolic acid) administered intraperitoneally in a constant dose of 300 mg/kg at various pretreatment times (i.e., 15, 30, 60 and 120 min.) before the MES test. Results indicate that only borneol produced a 75% protection against MES-induced tonic seizures in mice, when administered i.p. at 15 min. prior to the MES test. Borneol administered i.p. at 30 min before the MES test protected a 37.5% of animals tested, whereas the compound administered i.p. at 60 min. prior to the test exerted barely a 12.5% protection against MES-induced tonic seizures. In contrast, borneol administered i.p. at 120 min. prior to the test produced no anticonvulsant activity in mice subjected to the MES test. The remaining substances tested in the mouse MES model (i.e., arbutin, esculetin, esculin, ellagic acid, gallic acid, hesperidine, piperitol, piperonal, quercetin and ursolic acid) exerted no or negligible anti-seizure activity after their i.p. administration to mice. In conclusion, borneol is worthy of consideration as a potentially favorable compound in epileptology, if the results from this study could be extrapolated into clinical settings.
Caroli disease in magnetic resonance imagining
Authors: Burdan Franciszek , Mocarska Agnieszka , Kołodziej Lidia , Janczarek Marzena , Zymon Robert , Kiszka Joanna , Chruścicka Aneta , Żelazowska-Cieślińska Iwona , Starosławska Elżbieta
Published: October 2013

Caroli disease is a rare liver disorder, characterized by saccular or fusiform multifocal, segmental dilatation of the intrahepatic bile ducts. A new case of the disease diagnosed in a 38-years old male using magnetic resonance with virtual cholangiopancreatography is reported.
A comparison of the selectivity of nano-HPTLC systems used for determination of patulin in fruit juices from the internet stores and pharmacies
Authors: Przybylska Anna , Bazylak Grzegorz
Published: October 2013

The new nano-HPTLC method was proposed for improved separation of patulin from the admixture of the three naturally occurring natural components of fruit juices, which in last years could be often obtained from the internet functional food stores and pharmacies. Separation of patulin (P) from quercetin (Q), ascorbic acid (A) and 5-hydroxymethylfurfural (H) was performed using three different ready-for-use plates NanoAdamant (NA), Nano-SIL-20 (NSIL) and Nano-Durasil-20 (ND) covered with the non-modified silica gel layer. After development on the 8.0 cm distance, the nano-HPTLC plates were sprayed with 0.5% aqueous solution of the 3- methyl-benzothiazolinone hydrazone hydrochloride hydrate (MBTH). Most satisfactory separation of patulin from the each mentioned compounds was obtained using the Nano-SIL-20 plates and toluene-ethyl acetate-98% formic acid (25:20:5, v/v/v) as the mobile phase. In this best nano-HPLTC method the limit of detection of patulin was near 2.5 times lower (4 ng/spot) in comparison to other used here chromatographic systems. Thus, this optimized nano-HPTLC mode could be used for analysis of the solid-phase extracts of patulin from the fresh apples, clarified apple juices and other fruit products.
Determination of trace amounts of imazalil and thiabendazole in water- pipe “shisha” tobacco by UPLC-Q-TOF-MS
Authors: Szpot Paweł , Buszewicz Grzegorz
Published: October 2013

The paper presents a method for determination of trace amounts of imazalil and thiabendazole in water-pipe tobacco. Fungicides were isolated with diisopropyl ether and analyzed by ultra-performance liquid chromatograph coupled with quadrupole – time of flight mass spectrometer (UPLC-Q-TOF-MS). The method for determination of imazalil and thiabendazole is highly sensitive. The
lowest calibrated levels (LCL) were 0.2 ng/g and 10 ng/g respectively. Calibration curve was characterized by a very good linearity in the range for 0.2 – 100 ng/g for imazalil and 10 – 100 ng/g for thiabendazole (determination coefficient was 0.999 in both cases). The precisions (R.S.D.%) ranged from 1.56 % (imazalil) to 1.53 % (thiabendazole). Mean recovery was 129.44 % for imazalil and 84.73 % for thiabendazole. Usage of hybrid quadrupole coupled with time-of-flight analyzer characterized by a very high resolution allows to identify the investigated compounds and to apply the developed technique in routine quality control of fungicides in plant matrix.
Use of yeasts for prevention and therapy
Authors: Jach Monika Elżbieta , Sajnaga Ewa , Kozak Ewa , Malm Anna
Published: October 2013

Yeasts are a rich source of amino acids, proteins, several dietary minerals (e.g. chromium, selenium, zinc, iron, magnesium, cooper, manganese), and the B vitamins, particularly recommended for a vegan or vegetarian diet as well as for young people during maturation. One of the most well-known species of yeasts used in health and wellness is Saccharomyces cerevisiae (the common name is brewer’s yeast). They are often used as a source of B vitamins (B1, B2, B3, B5, B6, B7 and B9). Typically, brewer’s yeast is used as a protein, vitamin and mineral supplement, energy booster, immune enhancer, or vehicle where other compounds can be inserted to create a commercialized health product. The biomass of brewer’s yeast is also considered as an extensive source of bioavailable minerals, particularly chromium and selenium. Chromium is an essential trace mineral, since being part of glucose tolerance factor it helps the body maintain normal blood sugar levels, thereby decreasing appetite (especially for sweet foods). Another yeast species Yarrowia lipolytica contains high levels of many important nutrients, exogenous amino acids, proteins, different minerals, and lipid compounds as mainly unsaturated fatty acids (about 90%). This yeast species is a rich source of nutrients for vegans, vegetarians, athletes and a dietary supplement for people after recovery. Saccharomyces boulardii, a yeast species, has been found to be an effective probiotic. The clinical activity of S. boulardii is especially relevant to antibiotic-associated diarrhoea and recurrent Clostridium difficile intestinal infections. In conclusion, several studies indicate that nutritional yeasts as well as S. boulardii are important products for prophylactic and/or therapeutic purposes.
Methods of nanoliposomes preparation
Authors: Oksztulska Ewa
Published: October 2013

During the last decade, nanoliposomes have attracted great interest of many researchers. This was caused by unusual properties of these molecules, such us their nanosize, biocompatibility, and biodegradability. Due to these properties, they can be widely applied in many fields, especially as carriers of active substances in cosmetics, food technology, agriculture, and nanotherapy. The application of nanoliposomes as drug nanocarriers in medicine allows for more effective treatment of many diseases (e.g. cancers, atherosclerosis, ocular diseases) [1,6,7]. The advantage of these nanocarriers used in medicine is cell-specific targeting, which is indispensable to attain drug concentration, requisite for optimum therapeutic efficacy in the target site, with accompanying side effects limited to the minimum. Furthermore, the efficacy of treatment with these carriers comes from enhancing bioavailability, improving controlled release, and enabling precision targeting of the entrapped compounds, due to a larger increased surface area [7]. The aim of this paper is to present the current knowledge on the conventional methods of preparation of nanoliposomes, including microfluidization, extrusion, sonification technique, with particular emphasis on the advantages and disadvantages of each of these methods.