bluuebunny/crossref_metadata_2025 huggingface dataset:
Parental subsidies: The argument from insurance
Authors: Bou-Habib Paul
Published: June 2012

This article develops the argument that the state must provide parental subsidies if, and to the extent that, individuals would, under certain specified hypothetical conditions, purchase ‘insurance cover’ that would provide the funds they need for adequate childrearing. I argue that most citizens would sign up to an insurance scheme, in which they receive a guarantee of a means-tested parental subsidy in return for an obligation to pay a progressive income tax to fund the scheme. This argument from insurance bolsters the weaker case that proponents of parental subsidies might offer were they to rely exclusively on arguments from fair play and efficiency.
On waves propagating over two submerged closely spaced poroelastic breakwaters
Authors: Lan Yuan-Jyh , Kuo Yu-Shu , Hsu Tai-Wen , Chen Ching-Yu
Published: June 2012

In this paper, the problem of wave interactions created by two submerged closely spaced poroelastic breakwaters is investigated theoretically. An existing analytical solution is extended so as to be able to consider the problem subject to appropriate boundary conditions. The study domain is divided into seven sub-regions. Using general solutions for each region and matching kinematic and dynamic boundary conditions combined with an orthogonality condition, a set of simultaneous equations is developed; the individual equations being solved numerically. The analytical solutions are in agreement with the simplified cases of a submerged rigid breakwater, submerged permeable rigid breakwater and submerged poroelastic breakwater. Changes in the width of the two adjacent breakwaters, the effect of the permeability coefficient on wave profile, and the effect of materials and configurations of the breakwater on wave variation are the focus of the present paper. The presented results show that a large amount of energy is lost when the adjacent structures both have the same widths for a layer of a soft material with a high permeability. Different materials and shapes of structures can significantly influence the reflection coefficient.
Caregiver characteristics and economic cost of home-based care: a case study of Maun and Gumare villages in North West District, Botswana
Authors: Mmopelwa G , Ngwenya BN , Sinha N , Sanders JBP
Published: June 2012

The home-based care programme in Botswana was initiated partly to augment hospital or clinical care by reducing the healthcare costs associated with chronic illnesses such as HIV/AIDS. A number of studies have pointed to the psyco-social impacts of home based care, however there has been few attempts to quantify the direct and indirect costs associated with home based care. This study was carried out in the North West District of Botswana, which is noted for a relatively larger proportion of households with critically ill persons. The objectives of the study were to identify the characteristics of the caregivers and their patients; to estimate the direct and indirect costs of home-based care; and to estimate caregivers’ willingness to pay for care services. Data was collected using a structured questionnaire addressed to 120 primary caregivers and analyzed using SPSS. The economic cost of caregiving was estimated using the replacement cost method. The annual value per caregiver was estimated at P31 320 (US$4818.46). The study also revealed that more often than not, women are involved in caregiving activities.
Abiraterone and other novel androgen-directed strategies for the treatment of prostate cancer: a new era of hormonal therapies is born
Authors: Schweizer Michael T. , Antonarakis Emmanuel S.
Published: June 2012

The number of life-prolonging therapies proven effective in the treatment of metastatic castrate-resistant prostate cancer (CRPC) has been limited until recently. In the past 2 years several such therapies have come to market. In 2010, the autologous immunotherapy sipuleucel-T and the next-generation taxane cabazitaxel were approved in this setting. However, abundant evidence has shown that CRPC growth continues to be driven through androgen-dependent signaling. Both of these drugs fail to take advantage of this targetable oncogenic pathway. Potent specific inhibitors of cytochrome P450-17 have been engineered with the aim of suppressing androgen synthesis beyond that seen with the luteinizing hormone-releasing hormone agonists/antagonists. Abiraterone acetate was developed by rational design based on a pregnenolone parent structure. Its approval by the US Food and Drug Administration (FDA) was granted in 2011 based on phase III data demonstrating an overall survival advantage compared with placebo. More recently, other drugs that act along the androgen signaling pathway, such as orteronel (TAK-700), galeterone (TOK-001), enzalutamide (MDV3100) and ARN-509, have shown promise in clinical trials. Some of these are expected to gain FDA approval in the near future. Here, we review abiraterone and other novel androgen-directed therapeutic strategies for the management of advanced prostate cancer.
Effects of Cold Modality Application With Static and Intermittent Pneumatic Compression on Tissue Temperature and Systemic Cardiovascular Responses
Authors: Holwerda Seth W. , Trowbridge Cynthia A. , Womochel Kathryn S. , Keller David M.
Published: June 2012

Background:

In the therapeutic setting, cryotherapy with varying levels of intermittent cyclical compression often replaces an ice bag and elastic wrap. However, little is known about the cardiovascular strain and tissue temperature decreases associated with cooling and intermittent compression.

Hypothesis:

The authors hypothesized that higher levels of intermittent compression will result in greater reductions of tissue temperature and that all cold modalities will cause acute increases in cardiovascular strain.

Design:

Experimental crossover repeated measure design.

Methods:

Ten healthy subjects (23 ± 3 years) volunteered for 4 cryotherapy sessions (30-minute treatments with 30-minute passive recovery). Treatments included ice with elastic wrap and Game Ready (GR) with no, medium (5-50 mmHg), and high compression (5-75 mmHg). Throughout the experiment, oral, skin surface, and intramuscular quadriceps temperatures were measured along with mean arterial pressure, heart rate, rate pressure product, forearm blood flow, and forearm vascular conductance.

Results:

Mean arterial pressure increased up to 5 minutes ( P < 0.05). Forearm blood flow and forearm vascular conductance decreased after baseline ( P < 0.05), but there were no differences between treatments. Peak intramuscular changes from baseline were −14 ± 2°C (ice), −11 ± 6°C (GRHIGH), −10 ± 5°C (GRMED), and −7 ± 3°C (GRNO). Ice cooled the muscle the most, while GR with medium and high compression cooled more than GR without compression ( P < 0.05).

Conclusions:

The application of cold and intermittent pneumatic compression using GR did not produce acute cardiovascular strain that exceeded the strain produced by standard ice bags/elastic wrap treatment. Greater temperature decreases are achieved with medium- and high-pressure settings when using the GR system.

Clinical Relevance:

Type of cold and amount of compression affect tissue cooling in healthy lean subjects. All tested cold modalities caused acute increases in cardiovascular strain; however, these increases are no more than what healthy subjects experience with the onset of exercise.
Grade III Liver Laceration in a Female Volleyball Player
Authors: Milton Abby E. , Hansen Pamela J. , Miller Kevin C. , Rhee Yeong S.
Published: June 2012

A 20-year-old female collegiate volleyball athlete (body mass, 74.8 kg; height, 177.8 cm), with no previous history of abdominal injury, dove for a ball during a match and was struck in the anterolateral abdominal region by a teammate’s knee. She experienced a solar plexus spasm, shortness of breath, and nausea. On-site evaluation revealed sharp pain in the right upper quadrant and epigastric area, pallor, continued nausea, and excessive sweating. Upon arrival to the emergency department, an abdominal/pelvic computed tomography (CT) scan with intravenous contrast showed a small amount of fluid along the posteromedial surface of the liver indicating a subcapsular hematoma. A trace amount of free fluid in the right paracolic gutter and pelvis was also noted, suggesting a hemoperitoneum. The athlete was diagnosed with a grade III laceration (> 3 cm parenchymal depth) on the right lobe of the liver. She was hemodynamically stable and vital sign values were normal ~2.5 hours postinjury (blood pressure, 118/76 mm Hg; heart rate, 68 beats per minute; respiratory rate, 16 breaths per minute; tympanic temperature, 36.3°C). The athlete was admitted into the intensive care unit for observation, and the attending physician decided on a conservative, nonoperative approach to treatment. Forty-eight hours postinjury, a second abdominal/pelvic CT scan was ordered and revealed no increased bleeding or extensive damage to the liver. Two days later, after being discharged from the hospital, she was prohibited from practicing until a third abdominal/pelvic CT scan was performed and showed no residual injury to the liver (5 weeks postinjury). The athlete returned to play 6 weeks postinjury without complications; however, she continued performing rehabilitation focusing on cardiorespiratory endurance.
L-leucine improves the anemia and developmental defects associated with Diamond-Blackfan anemia and del(5q) MDS by activating the mTOR pathway
Authors: Payne Elspeth M. , Virgilio Maria , Narla Anupama , Sun Hong , Levine Michelle , Paw Barry H. , Berliner Nancy , Look A. Thomas , Ebert Benjamin L. , Khanna-Gupta Arati
Published: June 2012

Haploinsufficiency of ribosomal proteins (RPs) has been proposed to be the common basis for the anemia observed in Diamond-Blackfan anemia (DBA) and myelodysplastic syndrome with loss of chromosome 5q [del(5q) MDS]. We have modeled DBA and del(5q) MDS in zebrafish using antisense morpholinos to rps19 and rps14, respectively, and have demonstrated that, as in humans, haploinsufficient levels of these proteins lead to a profound anemia. To address the hypothesis that RP loss results in impaired mRNA translation, we treated Rps19 and Rps14-deficient embryos with the amino acid L-leucine, a known activator of mRNA translation. This resulted in a striking improvement of the anemia associated with RP loss. We confirmed our findings in primary human CD34+ cells, after shRNA knockdown of RPS19 and RPS14. Furthermore, we showed that loss of Rps19 or Rps14 activates the mTOR pathway, and this is accentuated by L-leucine in both Rps19 and Rps14 morphants. This effect could be abrogated by rapamycin suggesting that mTOR signaling may be responsible for the improvement in anemia associated with L-leucine. Our studies support the rationale for ongoing clinical trials of L-leucine as a therapeutic agent for DBA, and potentially for patients with del(5q) MDS.
Combined gene expression and DNA occupancy profiling identifies potential therapeutic targets of t(8;21) AML
Authors: Lo Miao-Chia , Peterson Luke F. , Yan Ming , Cong Xiuli , Jin Fulai , Shia Wei-Jong , Matsuura Shinobu , Ahn Eun-Young , Komeno Yukiko , Ly Minh , Ommen Hans B. , Chen I-Ming , Hokland Peter , Willman Cheryl L. , Ren Bing , Zhang Dong-Er
Published: June 2012

Chromosome translocation 8q22;21q22 [t(8;21)] is commonly associated with acute myeloid leukemia (AML), and the resulting AML1-ETO fusion proteins are involved in the pathogenesis of AML. To identify novel molecular and therapeutic targets, we performed combined gene expression microarray and promoter occupancy (ChIP-chip) profiling using Lin−/Sca1−/cKit+ cells, the major leukemia cell population, from an AML mouse model induced by AML1-ETO9a (AE9a). Approximately 30% of the identified common targets of microarray and ChIP-chip assays overlap with the human t(8;21)–gene expression molecular signature. CD45, a protein tyrosine phosphatase and a negative regulator of cytokine/growth factor receptor and JAK/STAT signaling, is among those targets. Its expression is substantially down-regulated in leukemia cells. Consequently, JAK/STAT signaling is enhanced. Re-expression of CD45 suppresses JAK/STAT activation, delays leukemia development, and promotes apoptosis of t(8;21)–positive cells. This study demonstrates the benefit of combining gene expression and promoter occupancy profiling assays to identify molecular and potential therapeutic targets in human cancers and describes a previously unappreciated signaling pathway involving t(8;21) fusion proteins, CD45, and JAK/STAT, which could be a potential novel target for treating t(8;21) AML.
A phase 2 trial of standard-dose cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab plus bevacizumab for patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: SWOG 0515
Authors: Stopeck Alison T. , Unger Joseph M. , Rimsza Lisa M. , LeBlanc Michael , Farnsworth Brent , Iannone Maria , Glenn Martha J. , Fisher Richard I. , Miller Thomas P.
Published: June 2012

S0515 was a phase 2 trial to determine whether the addition of bevacizumab to cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) plus rituximab (R-CHOP) would improve progression-free survival (PFS) without adding significant toxicity in patients with newly diagnosed advanced diffuse large B-cell lymphoma. A total of 73 patients were enrolled. For the 64 eligible patients, median age was 68 years, and 60% had International Prognostic Index scores more than or equal to 3. The observed 1- and 2-year PFS estimates were 77% and 69%, respectively. These PFS estimates were not statistically different from the expected PFS for this population if treated with R-CHOP alone. Grade 3 or higher toxicities were observed in 81% of patients, including 2 grade 5 events. The majority of serious toxicities were hematologic but also included 5 patients with gastrointestinal perforations, 4 patients with thrombotic events, and 11 patients who developed grade 2 or 3 left ventricular dysfunction. Higher baseline urine VEGF and plasma VCAM levels correlated with worse PFS and overall survival. In conclusion, the addition of bevacizumab to R-CHOP chemotherapy was not promising in terms of PFS and resulted in increased serious toxicities, especially cardiac and gastrointestinal perforations. This study is registered at www.clinicaltrials.gov as #NCT00121199.
A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma
Authors: Perry Anamarija M. , Cardesa-Salzmann Teresa M. , Meyer Paul N. , Colomo Luis , Smith Lynette M. , Fu Kai , Greiner Timothy C. , Delabie Jan , Gascoyne Randy D. , Rimsza Lisa , Jaffe Elaine S. , Ott German , Rosenwald Andreas , Braziel Rita M. , Tubbs Raymond , Cook James R. , Staudt Louis M. , Connors Joseph M. , Sehn Laurie H. , Vose Julie M. , López-Guillermo Armando , Campo Elias , Chan Wing C. , Weisenburger Dennis D.
Published: June 2012

Biologic factors that predict the survival of patients with a diffuse large B-cell lymphoma, such as cell of origin and stromal signatures, have been discovered by gene expression profiling. We attempted to simulate these gene expression profiling findings and create a new biologic prognostic model based on immunohistochemistry. We studied 199 patients (125 in the training set, 74 in the validation set) with de novo diffuse large B-cell lymphoma treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like therapies, and immunohistochemical stains were performed on paraffin-embedded tissue microarrays. In the model, 1 point was awarded for each adverse prognostic factor: nongerminal center B cell–like subtype, SPARC (secreted protein, acidic, and rich in cysteine) < 5%, and microvascular density quartile 4. The model using these 3 biologic markers was highly predictive of overall survival and event-free survival in multivariate analysis after adjusting for the International Prognostic Index in both the training and validation sets. This new model delineates 2 groups of patients, 1 with a low biologic score (0-1) and good survival and the other with a high score (2-3) and poor survival. This new biologic prognostic model could be used with the International Prognostic Index to stratify patients for novel or risk-adapted therapies.
Genome-wide SNP scan of pooled DNA reveals nonsense mutation in FGF20 in the scaleless line of featherless chickens
Authors: Wells Kirsty L , Hadad Yair , Ben-Avraham Danny , Hillel Jossi , Cahaner Avigdor , Headon Denis J
Published: June 2012

Background

Scaleless (sc/sc) chickens carry a single recessive mutation that causes a lack of almost all body feathers, as well as foot scales and spurs, due to a failure of skin patterning during embryogenesis. This spontaneous mutant line, first described in the 1950s, has been used extensively to explore the tissue interactions involved in ectodermal appendage formation in embryonic skin. Moreover, the trait is potentially useful in tropical agriculture due to the ability of featherless chickens to tolerate heat, which is at present a major constraint to efficient poultry meat production in hot climates. In the interests of enhancing our understanding of feather placode development, and to provide the poultry industry with a strategy to breed heat-tolerant meat-type chickens (broilers), we mapped and identified the sc mutation.

Results

Through a cost-effective and labour-efficient SNP array mapping approach using DNA from sc/sc and sc/+ blood sample pools, we map the sc trait to chromosome 4 and show that a nonsense mutation in FGF20 is completely associated with the sc/sc phenotype. This mutation, common to all sc/sc individuals and absent from wild type, is predicted to lead to loss of a highly conserved region of the FGF20 protein important for FGF signalling. In situ hybridisation and quantitative RT-PCR studies reveal that FGF20 is epidermally expressed during the early stages of feather placode patterning. In addition, we describe a dCAPS genotyping assay based on the mutation, developed to facilitate discrimination between wild type and sc alleles.

Conclusions

This work represents the first loss of function genetic evidence supporting a role for FGF ligand signalling in feather development, and suggests FGF20 as a novel central player in the development of vertebrate skin appendages, including hair follicles and exocrine glands. In addition, this is to our knowledge the first report describing the use of the chicken SNP array to map genes based on genotyping of DNA samples from pooled whole blood. The identification of the sc mutation has important implications for the future breeding of this potentially useful trait for the poultry industry, and our genotyping assay can facilitate its rapid introgression into production lines.
Molecular analysis of volatile metabolites released specifically by staphylococcus aureus and pseudomonas aeruginosa
Authors: Filipiak Wojciech , Sponring Andreas , Baur Maria Magdalena , Filipiak Anna , Ager Clemens , Wiesenhofer Helmut , Nagl Markus , Troppmair Jakob , Amann Anton
Published: June 2012

Background

The routinely used microbiological diagnosis of ventilator associated pneumonia (VAP) is time consuming and often requires invasive methods for collection of human specimens (e.g. bronchoscopy). Therefore, it is of utmost interest to develop a non-invasive method for the early detection of bacterial infection in ventilated patients, preferably allowing the identification of the specific pathogens. The present work is an attempt to identify pathogen-derived volatile biomarkers in breath that can be used for early and non- invasive diagnosis of ventilator associated pneumonia (VAP). For this purpose, in vitro experiments with bacteria most frequently found in VAP patients, i.e. Staphylococcus aureus and Pseudomonas aeruginosa, were performed to investigate the release or consumption of volatile organic compounds (VOCs).

Results

Headspace samples were collected and preconcentrated on multibed sorption tubes at different time points and subsequently analyzed with gas chromatography mass spectrometry (GC-MS). As many as 32 and 37 volatile metabolites were released by S. aureus and P. aeruginosa, respectively. Distinct differences in the bacteria-specific VOC profiles were found, especially with regard to aldehydes (e.g. acetaldehyde, 3-methylbutanal), which were taken up only by P. aeruginosa but released by S. aureus. Differences in concentration profiles were also found for acids (e.g. isovaleric acid), ketones (e.g. acetoin, 2-nonanone), hydrocarbons (e.g. 2-butene, 1,10-undecadiene), alcohols (e.g. 2-methyl-1-propanol, 2-butanol), esters (e.g. ethyl formate, methyl 2-methylbutyrate), volatile sulfur compounds (VSCs, e.g. dimethylsulfide) and volatile nitrogen compounds (VNCs, e.g. 3-methylpyrrole).

Importantly, a significant VOC release was found already 1.5 hours after culture start, corresponding to cell numbers of ~8*106 [CFUs/ml].

Conclusions

The results obtained provide strong evidence that the detection and perhaps even identification of bacteria could be achieved by determination of characteristic volatile metabolites, supporting the clinical use of breath-gas analysis as non-invasive method for early detection of bacterial lung infections.
Transcriptome analysis of amoeboid and ramified microglia isolated from the corpus callosum of rat brain
Authors: Parakalan Rangarajan , Jiang Boran , Nimmi Baby , Janani Manivannan , Jayapal Manikandan , Lu Jia , Tay Samuel SW , Ling Eng-Ang , Dheen S Thameem
Published: June 2012

Background

Microglia, the resident immune cells of the central nervous system (CNS), have two distinct phenotypes in the developing brain: amoeboid form, known to be amoeboid microglial cells (AMC) and ramified form, known to be ramified microglial cells (RMC). The AMC are characterized by being proliferative, phagocytic and migratory whereas the RMC are quiescent and exhibit a slow turnover rate. The AMC transform into RMC with advancing age, and this transformation is indicative of the gradual shift in the microglial functions. Both AMC and RMC respond to CNS inflammation, and they become hypertrophic when activated by trauma, infection or neurodegenerative stimuli. The molecular mechanisms and functional significance of morphological transformation of microglia during normal development and in disease conditions is not clear. It is hypothesized that AMC and RMC are functionally regulated by a specific set of genes encoding various signaling molecules and transcription factors.

Results

To address this, we carried out cDNA microarray analysis using lectin-labeled AMC and RMC isolated from frozen tissue sections of the corpus callosum of 5-day and 4-week old rat brain respectively, by laser capture microdissection. The global gene expression profiles of both microglial phenotypes were compared and the differentially expressed genes in AMC and RMC were clustered based on their functional annotations. This genome wide comparative analysis identified genes that are specific to AMC and RMC.

Conclusions

The novel and specific molecules identified from the trancriptome explains the quiescent state functioning of microglia in its two distinct morphological states.
Role of adventitious roots in water relations of tamarack (Larix laricina) seedlings exposed to flooding
Authors: Calvo-Polanco Mónica , Señorans Jorge , Zwiazek Janusz J
Published: June 2012

Background

Flooding reduces supply of oxygen to the roots affecting plant water uptake. Some flooding-tolerant tree species including tamarack (Larix laricina(Du Roi) K. Koch) produce adventitious roots in response to flooding. These roots were reported to have higher hydraulic conductivity under flooding conditions compared with non-adventitious roots. In the present study, we examined structural and functional modifications in adventitious roots of tamarack seedlings to explain their flooding tolerance.

Results

Seedlings were subjected to the flooding treatment for six months, which resulted in an almost complete disintegration of the existing root system and its replacement with adventitious roots. We compared gas exchange parameters and water relations of flooded plants with the plants growing in well-drained soil and examined the root structures and root water transport properties. Although flooded seedlings had lower needle chlorophyll concentrations, their stomatal conductance, net photosynthesis rates and shoot water potentials were similar to non-flooded plants, indicative of flooding tolerance. Flooded adventitious roots had higher activation energy and a higher ratio of apoplastic to cell-to-cell water flow compared with non-flooded control roots as determined with the 1-hydroxypirene 3,6,8-trisulfonic acid apoplastic tracer dye. The adventitious roots in flooded plants also exhibited retarded xylem and endodermal development and accumulated numerous starch grains in the cortex. Microscopic examination of root sections treated with the PIP1 and PIP2 antibodies revealed high immunoreactivity in the cortex of non-flooded roots, as compared with flooded roots.

Conclusions

Structural modifications of adventitious roots suggest increased contribution of apoplastic bypass to water flow. The reduced dependence of roots on the hypoxia-sensitive aquaporin-mediated water transport is likely among the main mechanisms allowing tamarack seedlings to maintain water balance and gas exchange under flooding conditions.
The role of TGFBI in mesothelioma and breast cancer: association with tumor suppression
Authors: Li Bingyan , Wen Gengyun , Zhao Yongliang , Tong Jian , Hei Tom K
Published: June 2012

Background

Transforming growth factor β induced (TGFBI) product, an extracellular matrix (ECM) protein, has been implicated as a putative tumor suppressor in recent studies. Our previous findings revealed that expression of TGFBI gene is down-regulated in a variety of cancer cell lines and clinical tissue samples. In this study, ectopic expression of TGFBI was used to ascertain its role as a tumor suppressor and to determine the underlying mechanism of mesothelioma and breast cancer.

Methods

Cells were stably transfected with pRc/CMV2-TGFBI and pRc/CMV2-empty vector with Lipofectamine Plus. Ectopic expression of TGFBI was quantified by using quantitative PCR and Western-blotting. Characterization of cell viability was assessed using growth curve, clonogenic survival and soft agar growth. The potential of tumor formation was evaluated by an in vivo mouse model. Cell cycle was analyzed via flow cytometry. Expressions of p21, p53, p16 and p14 were examined using Western-blotting. Senescent cells were sorted by using a Senescence β-Galactosidase Staining Kit. Telomerase activity was measured using quantitative telomerase detection kit.

Results

In this study, an ectopic expression of TGFBI in two types of cancer cell lines, a mesothelioma cell line NCI-H28 and a breast cancer cell line MDA-MB-231 was found to have reduced the cellular growth, plating efficiency, and anchorage-independent growth. The tumorigenicity of these cancer cell lines as determined by subcutaneous inoculation in nude mice was similarly suppressed by TGFBI expression. Likewise, TGFBI expression reduced the proportion of S-phase while increased the proportion of G1 phase in these cells. The redistribution of cell cycle phase after re-expression of TGFBI was correspondent with transiently elevated expression of p21 and p53. The activities of senescence-associated β-galactosidase and telomerase were enhanced in TGFBI-transfected cells.

Conclusion

Collectively, these results imply that TGFBI plays a suppressive role in the development of mesothelioma and breast cancer cells, possibly through inhibitions of cell proliferation, delaying of G1-S phase transition, and induction of senescence.
Effect of epimedium pubescen flavonoid on bone mineral status and bone turnover in male rats chronically exposed to cigarette smoke
Authors: Gao Shu-guang , Cheng Ling , Li Kang-hua , Liu Wen-He , Xu Mai , Jiang Wei , Wei Li-Cheng , Zhang Fang-jie , Xiao Wen-feng , Xiong Yi-lin , Tian Jian , Zeng Chao , Sun Jin-peng , Xie Qiang , Lei Guang-hua
Published: June 2012

Background

Epimedii herba is one of the most frequently used herbs in formulas that are prescribed for the treatment of osteoporosis in China and its main constituent is Epimedium pubescen flavonoid (EPF). However, it is unclear whether EPF during chronic exposure to cigarette smoke may have a protective influence on the skeleton. The present study investigated the effect of EPF on bone mineral status and bone turnover in a rat model of human relatively high exposure to cigarette smoke.

Methods

Fifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months. A rat model of passive smoking was prepared by breeding male rats in a cigarette-smoking box. Bone mineral content (BMC), bone mineral density (BMD), bone turnover markers, bone histomorphometric parameters and biomechanical properties were examined.

Results

Smoke exposure decreased BMC and BMD, increased bone turnover (inhibited bone formation and stimulated its resorption), affected bone histomorphometry (increased trabecular separation and osteoclast surface per bone surface; decreased trabecular bone volume, trabecular thickness, trabecular number, cortical thickness, bone formation rate and osteoblast surface per bone surface), and reduced mechanical properties. EPF supplementation during cigarette smoke exposure prevented smoke-induced changes in bone mineral status and bone turnover.

Conclusion

The results suggest that EPF can prevent the adverse effects of smoke exposure on bone by stimulating bone formation and inhibiting bone turnover and bone resorption.
Home and community based care program assessment for people living with HIV/AIDS in Arba Minch, Southern Ethiopia
Authors: Zerfu Taddese Alemu , Yaya Yaliso , Dagne Selamawit , Deribe Kebede , Ruiseñor-Escudero Horacio , Biadgilign Sibhatu
Published: June 2012

Background

People Living with HIV/AIDS (PLWHA) require significant care and support; however, most care needs are still unmet. To our knowledge, no studies have described the activities and challenges of care services in Ethiopia. Our objective was to assess the status, shortcomings and prospects of care and support services provided to PLWHA in the town of Arba Minch, Ethiopia, and surrounding areas.

Methods

A cross-sectional quantitative study combined with qualitative methods was conducted in Southern Ethiopia among 226 randomly selected PLWHAs and 10 service providers who were purposively selected. Data was collected using a pre-tested structured interview questionnaire and in-depth interview guideline. Quantitative data was analyzed using SPSS windows based statistical software while qualitative data was analyzed manually using thematic framework analysis.

Results

A total of 226 PLWHAs were interviewed. Socio-economic support (material and income generating activities) was being received by 108 (47.8%) of the respondents, counseling services (e.g. psychological support) were being received 128(56.6%), 144 (63.7%) alleviation of stigma and discrimination as human right and legal support for study participants. Inadequate external financial support, lack of proper referral systems between different care providers were among the reasons identified for the low quality and redundancy of care and support activities. Nonetheless, many opportunities and prospects, including easily accessible care receivers (PLWHA), good political and societal will were also implicated.

Conclusion

Care and support services provided to PLWHAs in the study area are by far lower in terms of coverage and quantity. Strategies for improvement could be facilitated given the observed political will, social support and access to care givers.
In vitro antimicrobial activity of ethanolic fractions of Cryptolepis sanguinolenta
Authors: Mills-Robertson Felix C , Tay Samuel CK , Duker-Eshun Goerge , Walana Williams , Badu Kingsley
Published: June 2012

Background

Following claims that some plants have antimicrobial activities against infectious microbes, the in vitro antimicrobial activities of different solvent fractions of ethanolic extract of Cryptolepis sanguinolenta were evaluated against eight standard bacteria and clinical isolates.

Methods

The solvent partitioning protocol involving ethanol, petroleum ether, chloroform, ethyl acetate and water, was used to extract various fractions of dried pulverized Cryptolepis sanguinolenta roots. Qualitative phyto-constituents screening was performed on the ethanol extract, chloroform fraction and the water fraction. The Kirby Bauer disk diffusion method was employed to ascertain the antibiogram of the test organisms while the agar diffusion method was used to investigate the antimicrobial properties of the crude plant extracts. The microplate dilution method aided in finding the MICs while the MBCs were obtained by the method of Nester and friends. The SPSS 16.0 version was used to analyze the percentages of inhibitions and bactericidal activities.

Results

The phytochemical screening revealed the presence of alkaloids, reducing sugars, polyuronides, anthocyanosides and triterpenes. The ethanol extract inhibited 5 out of 8 (62.5%) of the standard organisms and 6 out of 8 (75%) clinical isolates. The petroleum ether fraction inhibited 4 out of 8 (50%) of the standard microbes and 1 out of 8 (12.5%) clinical isolates. It was also observed that the chloroform fraction inhibited the growth of all the organisms (100%). Average inhibition zones of 14.0 ± 1.0 mm to 24.67 ± 0.58 mm was seen in the ethyl acetate fraction which halted the growth of 3 (37.5%) of the standard organisms. Inhibition of 7 (87.5%) of standard strains and 6 (75%) of clinical isolates were observed in the water fraction. The chloroform fraction exhibited bactericidal activity against all the test organisms while the remaining fractions showed varying degrees of bacteriostatic activity.

Conclusion

The study confirmed that fractions of Cryptolepis sanguinolenta have antimicrobial activity. The chloroform fraction had the highest activity, followed by water, ethanol, petroleum ether and ethyl acetate respectively. Only the chloroform fraction exhibited bactericidal activity and further investigations are needed to ascertain its safety and prospects of drug development.
Distance saturation product predicts health–related quality of life among sarcoidosis patients
Authors: Bourbonnais Julie M , Malaisamy Subramanian , Dalal Bhavinkumar D , Samarakoon Priyan C , Parikh Swapna R , Samavati Lobelia
Published: June 2012

Background

Sarcoidosis is a chronic disease with different phenotypic manifestations. Health-related quality of life is an important aspect in sarcoidosis, yet difficult to measure. The objective of this study was to identify clinical markers predictive of poor quality of life in sarcoidosis patients that can be followed over time and targeted for intervention.

Methods

We assessed the quality of life of 162 patients with confirmed sarcoidosis in a prospective, cross-sectional study using the Sarcoidosis Health Questionnaire (SHQ) and Short Form-36 Health Survey (SF-36). We evaluated the validity of these questionnaires and sought to identify variables that would best explain the performance scores of the patients.

Results

On multivariate regression analyses, the very best composite model to predict total scores from both surveys was a model containing the distance-saturation product and Borg Dyspnea Scale score at the end of a 6-min walk test. This model could better predict SF-36 scores (R2 = 0.33) than SHQ scores (R2 = 0.24). Substitution of distanced walked in 6 min for the distance-saturation product in this model resulted in a lesser ability to predict both scores (R2 = 0.26 for SF-36; R2 = 0.22 for SHQ).

Conclusions

Both the SHQ and SF-36 surveys are valuable tools in the assessment of health-related quality of life in sarcoidosis patients. The best model to predict quality of life among these patients, as determined by regression analyses, included the distance-saturation product and Borg score after the 6-min walk test. Both variables represent easily obtainable clinical parameters that can be followed over time and targeted for intervention.
Fluorescent magnetic nanoparticle-labeled mesenchymal stem cells for targeted imaging and hyperthermia therapy of in vivo gastric cancer
Authors: Ruan Jing , Ji Jiajia , Song Hua , Qian Qirong , Wang Kan , Wang Can , Cui Daxiang
Published: June 2012

How to find early gastric cancer cellsin vivois a great challenge for the diagnosis and therapy of gastric cancer. This study is aimed at investigating the feasibility of using fluorescent magnetic nanoparticle (FMNP)-labeled mesenchymal stem cells (MSCs) to realize targeted imaging and hyperthermia therapy ofin vivogastric cancer. The primary cultured mouse marrow MSCs were labeled with amino-modified FMNPs then intravenously injected into mouse model with subcutaneous gastric tumor, and then, thein vivodistribution of FMNP-labeled MSCs was observed by using fluorescence imaging system and magnetic resonance imaging system. After FMNP-labeled MSCs arrived in local tumor tissues, subcutaneous tumor tissues in nude mice were treated under external alternating magnetic field. The possible mechanism of MSCs targeting gastric cancer was investigated by using a micro-multiwell chemotaxis chamber assay. Results show that MSCs were labeled with FMNPs efficiently and kept stable fluorescent signal and magnetic properties within 14 days, FMNP-labeled MSCs could target and imagein vivogastric cancer cells after being intravenously injected for 14 days, FMNP-labeled MSCs could significantly inhibit the growth ofin vivogastric cancer because of hyperthermia effects, and CCL19/CCR7 and CXCL12/CXCR4 axis loops may play key roles in the targeting of MSCs toin vivogastric cancer. In conclusion, FMNP-labeled MSCs could targetin vivogastric cancer cells and have great potential in applications such as imaging, diagnosis, and hyperthermia therapy of early gastric cancer in the near future.
A single cidofovir treatment rescues animals at progressive stages of lethal orthopoxvirus disease
Authors: Israely Tomer , Paran Nir , Lustig Shlomo , Erez Noam , Politi Boaz , Shafferman Avigdor , Melamed Sharon
Published: June 2012

Background

In an event of a smallpox outbreak in humans, the window for efficacious treatment by vaccination with vaccinia viruses (VACV) is believed to be limited to the first few days post-exposure (p.e.). We recently demonstrated in a mouse model for human smallpox, that active immunization 2–3 days p.e. with either VACV-Lister or modified VACV Ankara (MVA) vaccines, can rescue animals from lethal challenge of ectromelia virus (ECTV), the causative agent of mousepox. The present study was carried out in order to determine whether a single dose of the anti-viral cidofovir (CDV), administered at different times and doses p.e. either alone or in conjunction with active vaccination, can rescue ECTV infected mice.

Methods

Animals were infected intranasally with ECTV, treated on different days with various single CDV doses and monitored for morbidity, mortality and humoral response. In addition, in order to determine the influence of CDV on the immune response following vaccination, both the "clinical take”, IFN-gamma and IgG Ab levels in the serum were evaluated as well as the ability of the mice to withstand a lethal challenge of ECTV. Finally the efficacy of a combined treatment regime of CDV and vaccination p.e. was determined.

Results

A single p.e. CDV treatment is sufficient for protection depending on the initiation time and dose (2.5 – 100 mg/kg) of treatment. Solid protection was achieved by a low dose (5 mg/kg) CDV treatment even if given at day 6 p.e., approximately 4 days before death of the control infected untreated mice (mean time to death (MTTD) 10.2). At the same time point complete protection was achieved by single treatment with higher doses of CDV (25 or 100 mg/kg). Irrespective of treatment dose, all surviving animals developed a protective immune response even when the CDV treatment was initiated one day p.e.. After seven days post treatment with the highest dose (100 mg/kg), virus was still detected in some organs (e.g. lung and liver) yet all animals survived, suggesting that efficacious single CDV treatment requires a potent immune system. The combination of CDV and vaccination provided no additional protection over CDV alone. Yet, combining CDV and vaccination maintained vaccination efficacy.

Conclusions

Altogether, our data substantiate the feasibility of single post-exposure antiviral treatment to face orthopoxvirus infection.
Prediction of response to pegylated-interferon-α and ribavirin therapy in Chinese patients infected with different hepatitis C virus genotype
Authors: Guo Xiaoyan , Zhao Zhixin , Xie Junqiang , Cai Qingxian , Zhang Xiaohong , Peng Liang , Gao Zhiliang
Published: June 2012

Background

The standard treatment for patients with chronic hepatitis C (CHC), pegylated interferon-α (PEG-IFN) plus ribavirin (RBV) does not provide a sustained virological response (SVR) in all patients. Genetic variations at the interleukin 28B (IL-28B) locus are important in predicting outcome following therapy in CHC patients.

Results

We investigated the role of IL28B variations (rs8099917) in response to PEG-IFN-α/RBV treatment and evaluated its association with the risk of the null virological response (NVR) and relapse (REL) in different viral genotypes. We found that the overall distributions of the genotype among the SVR, NVR, and REL groups were significantly different (P<0.001). Patients with the TG genotype had an increased risk of NVR and REL (OR=6.45 95% CI =2.88–14.47, P<0.001 for NVR; OR=2.51, 95% CI =1.29–4.86, P=0.006 for REL, respectively), and patients with the GG genotype had a further increased risk of NVR and REL (OR=12.04, 95% CI =3.21–45.13, P<0.001 for NVR; ,OR=4.30, 95% CI =1.21–15.13, P=0.017 for REL, respectively). G variant genotypes (TG+GG) also had an increased risk of NVR and REL, and there was a significant trend for a dose-effect of G allele on the risk of NVR and REL (P<0.05). The SVR rate in TT higher than in TG+GG was more pronounced in those patients infected with non-G1 compared to the patients infected with G1. The treatment response did differ based on the rs8099917 genotype in patients with different viral genotypes, compared with patients infected with the non-G1, the G1 infected patients had an increased risk of NVR and REL (OR=2.03 95% CI =1.03–4.01, P=0.04 for NVR and OR=2.58, 95% CI =1.35–4.94, P=0.004 for REL, respectively). Moreover, multivariate regression analysis show that the rs8099917 G allele was the only independent factor significantly associated with a NVR and REL.

Conclusion

This study suggests that host genetic polymorphisms rs8099917 in the vicinity of IL-28B is the most important predictor of treatment response of PEG-IFN-α/RBV for HCV patients in China.
Stimulation of the autonomic nervous system in colorectal surgery: a study protocol for a randomized controlled trial
Authors: Berghmans Tim MP , Hulsewé Karel WE , Buurman Wim A , Luyer Misha DP
Published: June 2012

Background

Postoperative ileus (POI) is a well-known complication of abdominal surgery and is considered to be caused by a local inflammation in the gut. Previously it has been shown that both local and systemic inflammation can be reduced by stimulation of the autonomic nervous system via lipid rich nutrition. Stimulation of the autonomic nervous system releases acetylcholine from efferent vagal nerve endings that binds to nicotinic receptors located on the inflammatory cells leading to a decrease of pro-inflammatory mediators. Besides administration of nutrition there are other ways of stimulating the autonomic nervous system such as gum chewing.

Methods/design

This prospective, placebo-controlled randomized trial will include 120 patients undergoing colorectal surgery which are randomized for gum chewing preoperatively and in the direct postoperative phase or a placebo. Postoperative ileus will be assessed both clinically by time to first flatus and time to first defecation and by determination of gastric motility using ultrasound to measure dimensions of the antrum. Furthermore the inflammatory response is quantified by analyzing pro-inflammatory mediators. Finally, markers of gut barrier integrity will be measured as well as occurrence of postoperative complications.

Discussion

We hypothesize that chewing gum preoperatively and in the direct postoperative phase in patients undergoing colorectal surgery dampens local and systematic inflammation, via activation of the autonomic nervous system. Down-regulation of the inflammatory cascade via stimulation of the vagus nerve will ameleriote POI and enhance postoperative recovery.

Trial registration

NTR2867
Oncogenic reg IV is a novel prognostic marker for glioma patient survival
Authors: Wang Qi , Deng Jianping , Yuan Jun , Wang Liang , Zhao Zhenwei , He Shiming , Zhang Yongsheng , Tu Yanyang
Published: June 2012

Aim

The aberrant expression of regenerating islet-derived family member, 4 (Reg IV) has been found in various human cancers. However, the roles of Reg IV gene and its encoding product in human glioma have not been clearly understood. Therefore, the aim of this study was to investigate the clinicopathological significance of Reg IV expression in glioma.

Methods

Reg IV mRNA and protein expression in human gliomas and non-neoplastic brain tissues were respectively detected by real-time quantitative RT-PCR assay, Western blot, and immunohistochemistry. The association of Reg IV immunostaining with clinicopathological factors and prognosis of glioma patients was also statistically analyzed.

Results

Reg IV mRNA and protein expression levels in glioma tissues were both significantly higher than those in the corresponding non-neoplastic brain tissues (both P < 0.001). Additionally, the increased Reg IV immunostaining in glioma tissues was significantly associated with advanced pathological grade (P = 0.008). Reg IV protein up-regulation was also significantly correlated with low Karnofsky performance score (KPS) (P = 0.02). Moreover, the overall survival of patients with high Reg IV protein expression was dramatically shorter than those with low Reg IV protein expression (P < 0.001). Multivariate Cox regression analysis further confirmed that Reg IV expression was an independent prognostic factor for patients with gliomas (P = 0.008).

Conclusions

These convinced evidences suggest for the first time that Reg IV might accelerate disease progression and act as a candidate prognostic marker for gliomas.

Virtual slides

The virtual slide(s) for this article can be found here:

http://www.diagnosticpathology.diagnomx.eu/vs/2145344361720706