bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct access colonoscopy in primary care: is it a safe and practical approach?
Authors: Ahmed J , Mehmood S , Khan SA , Rao MM
Published: August 2013

Background

Implementation of colorectal cancer screening programme and provision of cancer service within certain timeframe has significantly increased the workload on endoscopy services. Direct access colonoscopy in primary care centers helps offload burden on conventional colonoscopy in secondary care, thereby reducing waiting times. The aim of this study was to assess the safety and efficacy of direct access colonoscopy service.

Materials and methods

Provision of colonoscopy service in our healthcare trust was analysed retrospectively during a two-year period. Safety and feasibility of direct access colonoscopy was analysed against conventional colonoscopy. The groups were compared for findings at colonoscopy, procedural outcomes, and complications.

Results

A total of 3468 colonoscopies were analysed. Of those, 1189(34.3%) were performed as direct access colonoscopy and 2279(65.7%) as conventional colonoscopy. No abnormality was detected in 408/1189(34.3%) and 825/2279(36.2%) patients in the direct access colonoscopy and conventional colonoscopy groups, respectively ( p = 0.52). Colorectal cancer detection rate was similar between the groups; conventional colonoscopy vs direct access colonoscopy, 3.1% (68/2279) vs 3.2% (39/1189) ( p = 0.85). However, there was significantly higher detection rate of polyps greater than 1 cm in conventional colonoscopy group compared to direct access colonoscopy group, 22.6%(518/2289) vs 12.6% (150/1189) ( p = 0.02). Complication rates were comparable between the groups.

Conclusion

Direct access colonoscopy in primary care centers is safe and feasible. Colorectal cancer detection remains comparable to that of conventional colonoscopy in secondary care despite relatively lower polyp detection rate.
Hepatitis E: the West of Scotland experience
Authors: Deshpande A , Gunson R , Bradley A , Cameron S
Published: August 2013

Background and aims

Hepatitis E virus is traditionally regarded as a virus of the developing world and is emerging as a leading cause of non-A/B/C hepatitis. We wished to investigate locally acquired transmission of hepatitis E in the West of Scotland and compare our use of traditional serology versus polymerase chain reaction since the introduction of polymerase chain reaction in 2007.

Methods

Clinical details provided on specimens of blood positive for hepatitis E virus by serology or polymerase chain reaction were collated and analysed.

Results

Since 2007, 30 samples were hepatitis E virus-positive by serology or polymerase chain reaction. Polymerase chain reaction positivity was generally associated with positive serology although four samples were polymerase chain reaction-negative and strongly positive by serology. Interestingly, one-quarter of cases were likely to represent endogenous transmission of the infection.

Conclusions

Polymerase chain reaction is valuable in reliably diagnosing hepatitis E virus. However, serology is valuable for diagnosing resolved infection. There may be a high level of undiagnosed locally acquired hepatitis E virus in Scotland.
A New Kitchen for the World — Women, Politics and Religion
Authors: Gerle Elisabeth
Published: August 2013

Kitchen is also an image for a biblical generosity to the stranger, an expression of the ‘Hearthold of God’ and of mercy. A round table can be solid in a way that prevents hugging as well as fighting, yet a place where gestures of love can be expressed. My kitchen metaphor may also be read as claiming the sacrament of the kitchen table, of bread and wine in ordinary life.
‘And Truth—So Manifold!’—Transfeminist Entanglements
Authors: Keller Catherine
Published: August 2013

How are we theologically imagining feminism’s further becomings at this juncture of multiple intertwined uncertainties? Aided by a poem by Emily Dickinson, this meditation on a transfeminist (not postfeminist) potentiality within and beyond Christianity plies a trinity of entanglement (relationality), mystery (apophasis), and multiplicity (polydoxy).
Identification of a cellular ligand for the natural cytotoxicity receptor NKp44
Authors: Baychelier Florence , Sennepin Alexis , Ermonval Myriam , Dorgham Karim , Debré Patrice , Vieillard Vincent
Published: August 2013

Key Points

The cellular ligand of the NKp44L is a novel isoform of the mixed-lineage leukemia-5 protein. NKp44L is not expressed on healthy cells, but on tumor and transformed cells, rendering them more sensitive for the NK cytotoxicity.
De novo transcriptome assembly of drought tolerant CAM plants, Agave deserti and Agave tequilana
Authors: Gross Stephen M , Martin Jeffrey A , Simpson June , Abraham-Juarez María Jazmín , Wang Zhong , Visel Axel
Published: August 2013

Background

Agaves are succulent monocotyledonous plants native to xeric environments of North America. Because of their adaptations to their environment, including crassulacean acid metabolism (CAM, a water-efficient form of photosynthesis), and existing technologies for ethanol production, agaves have gained attention both as potential lignocellulosic bioenergy feedstocks and models for exploring plant responses to abiotic stress. However, the lack of comprehensiveAgavesequence datasets limits the scope of investigations into the molecular-genetic basis ofAgavetraits.

Results

Here, we present comprehensive, high qualityde novotranscriptome assemblies of twoAgavespecies,A. tequilanaandA. deserti,built from short-read RNA-seq data. Our analyses support completeness and accuracy of thede novotranscriptome assemblies, with each species having a minimum of approximately 35,000 protein-coding genes. Comparison of agave proteomes to those of additional plant species identifies biological functions of gene families displaying sequence divergence in agave species. Additionally, a focus on the transcriptomics of theA. desertijuvenile leaf confirms evolutionary conservation of monocotyledonous leaf physiology and development along the proximal-distal axis.

Conclusions

Our work presents a comprehensive transcriptome resource for twoAgavespecies and provides insight into their biology and physiology. These resources are a foundation for further investigation of agave biology and their improvement for bioenergy development.
The root transcriptome for North American ginseng assembled and profiled across seasonal development
Authors: Wu Di , Austin Ryan S , Zhou Sijun , Brown Dan
Published: August 2013

Background

Ginseng including North American ginseng (Panax quinquefolius L.) is one of the most widely used medicinal plants. Its success is thought to be due to a diverse collection of ginsenosides that serve as its major bioactive compounds. However, few genomic resources exist and the details concerning its various biosynthetic pathways remain poorly understood. As the root is the primary tissue harvested commercially for ginsenosides, next generation sequencing was applied to the characterization and assembly of the root transcriptome throughout seasonal development. Transcripts showing homology to ginsenoside biosynthesis enzymes were profiled in greater detail.

Results

RNA extracts from root samples from seven development stages of North American ginseng were subjected to 454 sequencing, filtered for quality and used in the de novo assembly of a collective root reference transcriptome consisting of 41,623 transcripts. Annotation efforts using a number of public databases resulted in detailed annotation information for 34,801 (84%) transcripts. In addition, 3,955 genes were assigned to metabolic pathways using the Kyoto Encyclopedia of Genes and Genomes. Among our results, we found all of the known enzymes involved in the ginsenoside backbone biosynthesis and used co-expression analysis to identify a number of candidate sequences involved in the latter stages ginsenoside biosynthesis pathway. Transcript profiles suggest ginsenoside biosynthesis occurs at distinct stages of development.

Conclusions

The assembly generated provides a comprehensive annotated reference for future transcriptomic study of North American ginseng. A collection of putative ginsenoside biosynthesis genes were identified and candidate genes predicted from the lesser understood downstream stages of biosynthesis. Transcript expression profiles across seasonal development suggest a primary dammarane-type ginsenoside biosynthesis occurs just prior to plant senescence, with secondary ginsenoside production occurring throughout development. Data from the study provide a valuable resource for conducting future ginsenoside biosynthesis research in this important medicinal plant.
Visit complexity, diagnostic uncertainty, and antibiotic prescribing for acute cough in primary care: a retrospective study
Authors: Whaley Lauren E , Businger Alexandra C , Dempsey Patrick P , Linder Jeffrey A
Published: August 2013

Background

Guidelines and performance measures recommend avoiding antibiotics for acute cough/acute bronchitis and presume visits are straightforward with simple diagnostic decision-making. We evaluated clinician-assigned diagnoses, diagnostic uncertainty, and antibiotic prescribing for acute cough visits in primary care.

Methods

We conducted a retrospective analysis of acute cough visits – cough lasting ≤21 days in adults 18–64 years old without chronic lung disease – in a primary care practice from March 2011 through June 2012.

Results

Of 56,301 visits, 962 (2%) were for acute cough. Clinicians diagnosed patients with 1, 2, or ≥ 3 cough-related diagnoses in 54%, 35%, and 11% of visits, respectively. The most common principal diagnoses were upper respiratory infection (46%), sinusitis (10%), acute bronchitis (9%), and pneumonia (8%). Clinicians prescribed antibiotics in 22% of all visits: 65% of visits with antibiotic-appropriate diagnoses and 4% of visits with non-antibiotic-appropriate diagnoses. Clinicians expressed diagnostic uncertainty in 16% of all visits: 43% of visits with antibiotic-appropriate diagnoses and 5% of visits with non-antibiotic-appropriate diagnoses. Clinicians expressed uncertainty more often when prescribing antibiotics than when not prescribing antibiotics (30% vs. 12%; p < 0.001). As the number of visit diagnoses increased from 1 to 2 to ≥ 3, clinicians were more likely to express diagnostic uncertainty (5%, 25%, 40%, respectively; p < 0.001) and prescribe antibiotics (16%, 25%, 41%, respectively; p < 0.001).

Conclusions

Acute cough may be more complex and have more diagnostic uncertainty than guidelines and performance measures presume. Efforts to reduce antibiotic prescribing for acute cough should address diagnostic complexity and uncertainty that clinicians face.
Preoperative core needle biopsy is accurate in determining molecular subtypes in invasive breast cancer
Authors: Chen Xiaosong , Sun Long , Mao Yan , Zhu Siji , Wu Jiayi , Huang Ou , Li Yafen , Chen Weiguo , Wang Jianhua , Yuan Ying , Fei Xiaochun , Jin Xiaolong , Shen Kunwei
Published: August 2013

Background

Estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki67 have been increasingly evaluated by core needle biopsy (CNB) and are recommended for classifying breast cancer into molecular subtypes. However, the concordance rate between CNB and open excision biopsy (OEB) has not been well documented.

Methods

Patients with paired CNB and OEB samples from Oct. 2009 to Feb. 2012 in Ruijin Hospital were included. ER, PgR, HER2, and Ki67 were determined by immunohistochemistry (IHC). Patients with HER2 IHC 2+ were further examined by FISH. Cutoff value for Ki67 high expression was 14%. Molecular subtypes were constructed as follows: Luminal A, Luminal B, Triple Negative, and HER2 positive.

Results

There were 298 invasive breast cancer patients analyzed. Concordance rates for ER, PgR, and HER2 were 93.6%, 85.9%, and 96.3%, respectively. Ki67 expression was slightly higher in OEB than in CNB samples (29.3% vs. 26.8%, P = 0.046). Good agreement (κ = 0.658) was demonstrated in evaluating molecular subtypes between CNB and OEB, with a concordance rate of 77.2%. We also used a different Ki67 cutoff value (20%) for determining Luminal A and B subtypes in HR (hormone receptor) +/HER2- diseases and the overall concordance rate was 79.2%. However, using a cut-point of Ki67 either 14% or 20% for both specimens, there will be about 14% of HR+/HER2- specimens that are called Luminal A on CNB and Luminal B on OEB.

Conclusion

CNB was accurate in determining ER, PgR, and HER2 status as well as non-Luminal molecular subtypes in invasive breast cancer. Ki67 should be retested on OEB samples in HR+/HER2- patients to accurately distinguish Luminal A from B tumors.
No correlation between slip reduction in low-grade spondylolisthesis or change in neuroforaminal morphology and clinical outcome
Authors: Hagenmaier HS Femke , Delawi Diyar , Verschoor Nico , Oner F Cumhur , van Susante Job LC
Published: August 2013

Background

In instrumented posterolateral fusion reduction of a spondylolisthesis is appealing on theoretical grounds since this may lead to indirect decompression of the entrapped nerve roots. However, there is no consensus in the literature whether a beneficial effect of reduction on outcome can be expected. The objective of the current study was to evaluate whether a correlation between the extent of listhesis reduction and clinical improvement could be established.

Methods

From two ongoing prospective studies 72 patients with a single-level instrumented posterolateral lumbar fusion for low-grade spondylolisthesis (isthmic/degenerative 51/21) were evaluated. Radiographs and clinical outcome scores were available at baseline, 6 weeks and 1 year after surgery. Changes in neuroforaminal morphology were measured on calibrated radiographs. These changes in radiographic parameters were correlated to clinical outcome (Visual Analogue Score (VAS) leg pain, Oswestry Disability Index (ODI)). Fusion status was assessed on Computed Tomography-scan at one year.

Results

A mean spondylolisthesis of 25 percent was reduced to 15 percent at 6 weeks with some loss of reduction to 17 percent at one year. The VAS and ODI significantly improved at both time intervals after surgery (p < 0.001). No significant correlations could be established between the extent of slip reduction and improvement in VAS or ODI (Pearson’s correlation −0.2 and 0.07 respectively at one year); this also accounted for the other radiographic parameters. A fusion rate of 64 percent was seen on CT-scan.

Conclusions

Clinical outcome was not related to the obtained radiographic reduction of the slipped vertebra in patients with a lumbar fusion for low grade spondylolisthesis. Loss of reduction or non-union on CT-scans had no effect on the clinical outcome. Reduction of a low-grade spondylolisthesis in spinal fusion is appealing, however, there is no evidence that it positively affects clinical outcome on the short term.

Trial registration

ISRCTN43648350
Treatment and referral patterns for psoriasis in United Kingdom primary care: a retrospective cohort study
Authors: Khalid Javaria Mona , Globe Gary , Fox Kathleen M , Chau Dina , Maguire Andrew , Chiou Chio-Fang
Published: August 2013

Background

In the UK, referrals to specialists are initiated by general practitioners (GPs). Study objectives were to estimate the incidence of diagnosed psoriasis in the UK and identify factors associated with GP referrals to dermatologists.

Methods

Newly diagnosed patients with psoriasis were identified in The Health Improvement Network (THIN) database between 01 July 2007-31 Oct 2009. Incidence of diagnosed psoriasis was calculated using the number of new psoriasis patients in 2008 and the mid-year total patient count for THIN in 2008. A nested case–control design and conditional logistic regression were used to identify factors associated with referral.

Results

Incidence rate of diagnosed adult psoriasis in 2008 was 28/10,000 person-years. Referral rate to dermatologists was 18.1 (17.3-18.9) per 100 person-years. In the referred cohort (N=1,950), 61% were referred within 30 days of diagnosis and their median time to referral was 0 days from diagnosis. For those referred after 30 days (39%, median time to referral: 5.6 months), an increase in the number of GP visits prior to referral increased the likelihood of referral (OR=1.87 95% CI:1.73-2.01). A prescription of topical agents such as vitamin D3 analogues 30 days before referral increased the likelihood of being referred (OR=4.67 95% CI: 2.78-7.84), as did corticosteroids (OR=2.45 95% CI: 1.45-4.07) and tar products (OR=1.95 95% CI: 1.02-3.75).

Conclusions

Estimates of the incidence of diagnosed adult psoriasis, referral rates to dermatologists, and characteristics of referred patients may assist in understanding the burden on the UK healthcare system and managing this population in primary and secondary care.
Risk indicators of oral health status among young adults aged 18 years analyzed by negative binomial regression
Authors: Lu Hai-Xia , Wong May Chun Mei , Lo Edward Chin Man , McGrath Colman
Published: August 2013

Background

Limited information on oral health status for young adults aged 18 year-olds is known, and no available data exists in Hong Kong. The aims of this study were to investigate the oral health status and its risk indicators among young adults in Hong Kong using negative binomial regression.

Methods

A survey was conducted in a representative sample of Hong Kong young adults aged 18 years. Clinical examinations were taken to assess oral health status using DMFT index and Community Periodontal Index (CPI) according to WHO criteria. Negative binomial regressions for DMFT score and the number of sextants with healthy gums were performed to identify the risk indicators of oral health status.

Results

A total of 324 young adults were examined. Prevalence of dental caries experience among the subjects was 59% and the overall mean DMFT score was 1.4. Most subjects (95%) had a score of 2 as their highest CPI score. Negative binomial regression analyses revealed that subjects who had a dental visit within 3 years had significantly higher DMFT scores (IRR = 1.68, p < 0.001). Subjects who brushed their teeth more frequently (IRR = 1.93, p < 0.001) and those with better dental knowledge (IRR = 1.09, p = 0.002) had significantly more sextants with healthy gums.

Conclusions

Dental caries experience of the young adults aged 18 years in Hong Kong was not high but their periodontal condition was unsatisfactory. Their oral health status was related to their dental visit behavior, oral hygiene habit, and oral health knowledge.
Moringa Oleifera aqueous leaf extract down-regulates nuclear factor-kappaB and increases cytotoxic effect of chemotherapy in pancreatic cancer cells
Authors: Berkovich Liron , Earon Gideon , Ron Ilan , Rimmon Adam , Vexler Akiva , Lev-Ari Shahar
Published: August 2013

Background

Fewer than 6% patients with adenocarcinoma of the pancreas live up to five years after diagnosis. Chemotherapy is currently the standard treatment, however, these tumors often develop drug resistance over time. Agents for increasing the cytotoxic effects of chemotherapy or reducing the cancer cells’ chemo-resistance to the drugs are required to improve treatment outcome. Nuclear factor kappa B (NF-kB), a pro-inflammatory transcription factor, reportedly plays a significant role in the resistance of pancreatic cancer cells to apoptosis-based chemotherapy. This study investigated the effect of aqueous Moringa Oleifera leaf extract on cultured human pancreatic cancer cells - Panc-1, p34, and COLO 357, and whether it can potentiates the effect of cisplatin chemotherapy on these cells.

Methods

The effect of Moringa Oleifera leaf extract alone and in combination with cisplatin on the survival of cultured human pancreatic cancer cells was evaluated by XTT-based colorimetric assay. The distribution of Panc-1 cells in the cell cycle following treatment with Moringa leaf extract was evaluated by flow cytometry, and evaluations of protein levels were via immunoblotting. Data of cell survival following combined treatments were analyzed with Calcusyn software.

Results

Moringa Oleifera leaf extract inhibited the growth of all pancreatic cell lines tested. This effect was significant in all cells following exposure to ≥0.75 mg/ml of the extract. Exposure of Panc-1 cells to Moringa leaf extract induced an elevation in the sub-G1 cell population of the cell-cycle, and reduced the expression of p65, p-IkBα and IkBα proteins in crude cell extracts. Lastly, Moringa Oleifera leaf extract synergistically enhanced the cytotoxic effect of cisplatin on Panc-1 cells.

Conclusion

Moringa Oleifera leaf extract inhibits the growth of pancreatic cancer cells, the cells NF-κB signaling pathway, and increases the efficacy of chemotherapy in human pancreatic cancer cells.
The Care Process Self-Evaluation Tool: a valid and reliable instrument for measuring care process organization of health care teams
Authors: Seys Deborah , Deneckere Svin , Sermeus Walter , Gerven Eva Van , Panella Massimiliano , Bruyneel Luk , Mutsvari Timothy , Bejarano Rafaela Camacho , Kul Seval , Vanhaecht Kris
Published: August 2013

Background

Patient safety can be increased by improving the organization of care. A tool that evaluates the actual organization of care, as perceived by multidisciplinary teams, is the Care Process Self-Evaluation Tool (CPSET). CPSET was developed in 2007 and includes 29 items in five subscales: (a) patient-focused organization, (b) coordination of the care process, (c) collaboration with primary care, (d) communication with patients and family, and (e) follow-up of the care process. The goal of the present study was to further evaluate the psychometric properties of the CPSET at the team and hospital levels and to compile a cutoff score table.

Methods

The psychometric properties of the CPSET were assessed in a multicenter study in Belgium and the Netherlands. In total, 3139 team members from 114 hospitals participated. Psychometric properties were evaluated by using confirmatory factor analysis (CFA), Cronbach’s alpha, interclass correlation coefficients (ICCs), Kruskall-Wallis test, and Mann–Whitney test. For the cutoff score table, percentiles were used. Demographic variables were also evaluated.

Results

CFA showed a good model fit: a normed fit index of 0.93, a comparative fit index of 0.94, an adjusted goodness-of-fit index of 0.87, and a root mean square error of approximation of 0.06. Cronbach’s alpha values were between 0.869 and 0.950. The team-level ICCs varied between 0.127 and 0.232 and were higher than those at the hospital level (0.071-0.151). Male team members scored significantly higher than females on 2 of the 5 subscales and on the overall CPSET. There were also significant differences among age groups. Medical doctors scored significantly higher on 4 of the 5 subscales and on the overall CPSET. Coordinators of care processes scored significantly lower on 2 of the 5 subscales and on the overall CPSET. Cutoff scores for all subscales and the overall CPSET were calculated.

Conclusions

The CPSET is a valid and reliable instrument for health care teams to measure the extent care processes are organized. The cutoff table permits teams to compare how they perceive the organization of their care process relative to other teams.
Early innate immunity determines outcome of Mycobacterium tuberculosis pulmonary infection in rabbits
Authors: Subbian Selvakumar , Bandyopadhyay Nirmalya , Tsenova Liana , O’Brien Paul , Khetani Viraj , Kushner Nicole L , Peixoto Blas , Soteropoulos Patricia , Bader Joel S , Karakousis Petros C , Fallows Dorothy , Kaplan Gilla
Published: August 2013

Background

Pulmonary infection of humans byMycobacterium tuberculosis(Mtb), the causative agent of tuberculosis (TB), results in active disease in 5-10% of individuals, while asymptomatic latent Mtb infection (LTBI) is established in the remainder. The host immune responses that determine this differential outcome following Mtb infection are not fully understood. Using a rabbit model of pulmonary TB, we have shown that infection with the Mtb clinical isolate HN878 (a hyper-virulent W-Beijing lineage strain) leads to progressive cavitary disease similar to what is seen in humans with active TB. In contrast, infection with Mtb CDC1551 (a hyper-immunogenic clinical isolate) is efficiently controlled in rabbit lungs, with establishment of LTBI, which can be reactivated upon treatment with immune-suppressive drugs. We hypothesize that the initial interaction of Mtb with the cells of the host response in the lungs determine later outcome of infection.

Results

To test this hypothesis, we used our rabbit model of pulmonary TB and infected the animals with Mtb HN878 or CDC1551. At 3 hours, with similar lung bacillary loads, HN878 infection caused greater accumulation of mononuclear and polymorphonuclear leukocytes (PMN) in the lungs, compared to animals infected with CDC1551. Using whole-genome microarray gene expression analysis, we delineated the early transcriptional changes in the lungs of HN878- or CDC1551-infected rabbits at this time and compared them to the differential response at 4 weeks of Mtb-infection. Our gene network and pathway analysis showed that the most significantly differentially expressed genes involved in the host response to HN878, compared to CDC1551, at 3 hours of infection, were components of the inflammatory response and STAT1 activation, recruitment and activation of macrophages, PMN, and fMLP (N-formyl-Methionyl-Leucyl-Phenylalanine)-stimulation. At 4 weeks, the CDC1551 bacillary load was significantly lower and the granulomatous response reduced compared to HN878 infection. Moreover, although inflammation was dampened in both Mtb infections at 4 weeks, the majority of the differentially expressed gene networks were similar to those seen at 3 hours.

Conclusions

We propose that differential regulation of the inflammation-associated innate immune response and related gene expression changes seen at 3 hours determine the long term outcome of Mtb infection in rabbit lungs.
Anterior cruciate ligament surgery in the rabbit
Authors: Bachy Manon , Sherifi Ines , Zadegan Fréderic , Petrover David , Petite Hervé , Hannouche Didier
Published: August 2013

Background

Various methods regarding allograft knee replacements have been described. The animal models, which are generally used for this purpose include sheep, dogs, goats, and pigs, and accrue significant costs for study protocols. The authors herein describe an efficient and cost-effective model to study either native or tissue-engineered allografts for anterior cruciate ligament (ACL) replacement in a New Zealand rabbit model with the potential for transgenic and cell migration studies.

Methods

ACL reconstructions were performed in rabbits under general anesthesia. For fresh allograft implantations, two animals were operated in parallel. Each right extensor digitorum longus tendon was harvested and prepared for implantation. After excision of the ACL, tibial and femoral bone tunnels were created to implant each graft in the native ACL position.

Results

During a 2-year period, the authors have successfully undertaken this surgery in 61 rabbits and have not noticed any major complications attributed to this surgical technique. In addition, the authors have observed fast recovery in the animals postoperatively.

Conclusion

The authors recommend this surgical procedure as an excellent model for the study of knee surgery.
Ibrutinib and novel BTK inhibitors in clinical development
Authors: Akinleye Akintunde , Chen Yamei , Mukhi Nikhil , Song Yongping , Liu Delong
Published: August 2013

Small molecule inhibitors targeting dysregulated pathways (RAS/RAF/MEK, PI3K/AKT/mTOR, JAK/STAT) have significantly improved clinical outcomes in cancer patients. Recently Bruton’s tyrosine kinase (BTK), a crucial terminal kinase enzyme in the B-cell antigen receptor (BCR) signaling pathway, has emerged as an attractive target for therapeutic intervention in human malignancies and autoimmune disorders. Ibrutinib, a novel first-in-human BTK-inhibitor, has demonstrated clinical effectiveness and tolerability in early clinical trials and has progressed into phase III trials. However, additional research is necessary to identify the optimal dosing schedule, as well as patients most likely to benefit from BTK inhibition. This review summarizes preclinical and clinical development of ibrutinib and other novel BTK inhibitors (GDC-0834, CGI-560, CGI-1746, HM-71224, CC-292, and ONO-4059, CNX-774, LFM-A13) in the treatment of B-cell malignancies and autoimmune disorders.
PAX8: a sensitive and specific marker to identify cancer cells of ovarian origin for patients prior to neoadjuvant chemotherapy
Authors: Wang Yue , Wang Yiying , Li Jie , Yuan Zeng , Yuan Bingbing , Zhang Tingguo , Cragun Janiel M , Kong Beihua , Zheng Wenxin
Published: August 2013

Background

Neoadjuvant chemotherapy followed by cytoreduction surgery has been used where an accurate cytologic or pathologic diagnosis is usually required before the initiation of neoadjuvant chemotherapy. However, it is difficult to make definitive diagnosis of presence of cancer cells, particularly gynecologic versus non-gynecologic origin, from those ascites specimens due to the absence of specific biomarkers of gynecologic cancers. In the present study, we evaluated if, in addition to the routine morphologic diagnosis, the biomarker PAX8 could be useful in recognition of ovarian epithelial cancer cells prior to the neoadjuvant chemotherapy.

Methods

Two hundred and two cytology specimens including 120 pretreatment ovarian cancer samples, 60 benign controls, and 22 malignant non-gynecologic cases were studied. All cytology slides were morphologically reviewed in a blinded fashion without knowing corresponding pathology diagnosis, if present. A total of 168 cytology specimens with a cell block were stained with PAX8 and Calretinin. These included patients with potential for ovarian cancer neoadjuvant chemotherapy (n = 96), metastatic cancers (n = 22), and benign controls (n = 50).

Results

Among the 96 ascitic samples prior to neoadjuvant chemotherapy, 76 (79%) showing morphologic features consistent with cancers of ovarian primary were all PAX+/Calretinin-. The remaining 20 (21%) cases were positive for adenocarcinoma, but morphologically unable to be further classified. Among the 22 metastatic cancers into the pelvis, one case with PAX8+/Calretinin- represented a renal cell carcinoma and the remaining 21 PAX8-/Calretinin- metastatic cancers were either breast metastasis (n = 4) and the metastasis from gastrointestinal tract (n = 17). Among the 50 benign control pelvic washing cases, 5 PAX8+/Calretinin-cases represented endosalpingiosis (n = 4) and endometriosis (n = 1), 25 PAX8-/Calretinin + cases showed reactive mesothelial cells, and the remaining 20 specimens with PAX8-/Calretinin- phenotype typically contained inflammatory or blood cells without noticeable diagnostic epithelia.

Conclusions

PAX8 identifies all Müllerian derived benign or malignant epithelia. When combining with Calretinin, PAX8 is a sensitive marker to diagnose the carcinomas of ovarian origin, which will be ideal to be used for those patients with a possible advanced ovarian cancer prior to receiving neoadjuvant chemotherapy.
Inhibitory activities of acteoside, isoacteoside, and its structural constituents against protein glycation in vitro
Authors: Liu Yuh-Hwa , Lu Yeh-Lin , Han Chuan-Hsiao , Hou Wen-Chi
Published: August 2013

Background

Advanced glycation end products (AGE) are substances that can induce insulin resistance in adipocyte, hepatocyte and muscle cells. This resistance correlates highly with cardiovascular disease and diabetic complications. Acteoside (A), a phenylethanoid glycoside, is an active compound in several plants and traditional herbal medicines. Acteoside, its structural isomer, isoacteoside (I), and their constituents, caffeic acid (C) and 3,4-dihydroxyphenylethanol (D), were used in the study to investigate the inhibitory activity against AGE formations in vitro.

Results

AGE formations were detected by anti-(Nϵ-(carboxymethyl)lysine (anti-CML), using bovine serum albumin (BSA)/glucose (glc) and BSA/galactose (gal) as models, or by anti-argpyrimidine (anti-AP), using BSA/methylglyoxal (MGO) as models. It was found that A, I, C, or D, each at 5 mM, could attenuate the CML formations detected by ELISA in the BSA/gal model of a 3-day or 5-day reaction, and showed significant differences (P < 0.01 or P < 0.001) compared to the control. However, these compounds showed a minor effect after a 7-day incubation. It was also found that C or D could lower the CML formations in the BSA/glc model and showed significant differences (P < 0.05 or P < 0.01) compared to the control after a 3-day, 5-day and 7-day reaction. It was found that A, I, C, or D, each at 0.5 mM or 5 mM, could attenuate the AP formations in the BSA/MGO model of a 3-day reaction and showed significant differences (P < 0.001) compared to the control.

Conclusions

The results suggest the potential anti-glycation activities of A and I in vitro may apply to cell models at higher glucose concentrations or to diabetic animal models, and need further investigation.
Factors associated with wait times across the breast cancer treatment pathway in Ontario
Authors: Plotogea Amalia , Chiarelli Anna M , Mirea Lucia , Prummel Maegan V , Chong Nelson , Shumak Rene S , O’Malley Frances P , Holloway Claire M B ,   the Breast Screening Study Group
Published: August 2013

Background

Longer times from diagnosis to breast cancer treatment are associated with poorer prognosis. This study examined factors associated with wait times by phase in the breast cancer treatment pathway.

Methods

There were 1760 women eligible for the study, aged 50–69 diagnosed in Ontario with invasive breast cancer from 1995–2003. Multivariate logistic regression examined factors associated with greater than median wait times for each phase of the treatment pathway; from diagnosis to definitive surgery; from final surgery to radiotherapy without chemotherapy and from final surgery to chemotherapy.

Results

The median wait times were 17 days (Inter Quartile Range (IQR) = 0–31) from diagnosis to definitive surgery, 44 days (IQR = 34–56) from final surgery to postoperative chemotherapy and 75 days (IQR = 57–97) from final surgery to postoperative radiotherapy. Diagnosis during 2000–2003 compared to 1995–1999 was associated with significantly longer wait times for each phase of the treatment pathway. Higher income quintile was associated with longer wait time from diagnosis to surgery (OR = 1.47, 95% CI = 1.05-2.06) and shorter wait times from final surgery to radiotherapy (OR = 0.60, 95% CI = 0.37-0.96). Greater stage at diagnosis was associated with shorter wait times from diagnosis to definitive surgery (stage III vs I: OR = 0.49, 95% CI = 0.34-0.71).

Conclusions

While diagnosis during the latter part of the study period was associated with significantly longer wait times for all phases of the treatment pathway, there were variations in the associations of stage and income quintile with wait times by treatment phase. Continued assessment of factors associated with wait times across the breast cancer treatment pathway is important, as they indicate areas to be targeted for quality improvement with the ultimate goal of improving prognosis.
Fixed point results on subgraphs of directed graphs
Authors: Aleomraninejad SMA , Rezapour Sh , Shahzad N
Published: August 2013

In this paper, we obtain some fixed point results on subgraphs of directed graphs. We show that the Caristi fixed point theorem and a version of Knaster-Tarski fixed point theorem are special cases of our results.

2010 MSC

47H10; 05C20; 54H25
Hyperoxemia and long-term outcome after traumatic brain injury
Authors: Raj Rahul , Bendel Stepani , Reinikainen Matti , Kivisaari Riku , Siironen Jari , Lång Maarit , Skrifvars Markus
Published: August 2013

Introduction

The relationship between hyperoxemia and outcome in patients with traumatic brain injury (TBI) is controversial. We sought to investigate the independent relationship between hyperoxemia and long-term mortality in patients with moderate-to-severe traumatic brain injury.

Methods

The Finnish Intensive Care Consortium database was screened for mechanically ventilated patients with a moderate-to-severe TBI. Patients were categorized, according to the highest measured alveolar-arterial O2 gradient or the lowest measured PaO2 value during the first 24 hours of ICU admission, to hypoxemia (<10.0 kPa), normoxemia (10.0 to 13.3 kPa) and hyperoxemia (>13.3 kPa). We adjusted for markers of illness severity to evaluate the independent relationship between hyperoxemia and 6-month mortality.

Results

A total of 1,116 patients were included in the study, of which 16% (n = 174) were hypoxemic, 51% (n = 567) normoxemic and 33% (n = 375) hyperoxemic. The total 6-month mortality was 39% (n = 435). A significant association between hyperoxemia and a decreased risk of mortality was found in univariate analysis (P = 0.012). However, after adjusting for markers of illness severity in a multivariate logistic regression model hyperoxemia showed no independent relationship with 6-month mortality (hyperoxemia vs. normoxemia OR 0.88, 95% CI 0. 63 to 1.22, P = 0.43; hyperoxemia vs. hypoxemia OR 0.97, 95% CI 0.63 to 1.50, P = 0.90).

Conclusion

Hyperoxemia in the first 24 hours of ICU admission after a moderate-to-severe TBI is not predictive of 6-month mortality.
Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function
Authors: Ivanov Maxim , Kals Mart , Kacevska Marina , Barragan Isabel , Kasuga Kie , Rane Anders , Metspalu Andres , Milani Lili , Ingelman-Sundberg Magnus
Published: August 2013

Background

Interindividual differences in liver functions such as protein synthesis, lipid and carbohydrate metabolism and drug metabolism are influenced by epigenetic factors. The role of the epigenetic machinery in such processes has, however, been barely investigated. 5-hydroxymethylcytosine (5hmC) is a recently re-discovered epigenetic DNA modification that plays an important role in the control of gene expression.

Results

In this study, we investigate 5hmC occurrence and genomic distribution in 8 fetal and 7 adult human liver samples in relation to ontogeny and function. LC-MS analysis shows that in the adult liver samples 5hmC comprises up to 1% of the total cytosine content, whereas in all fetal livers it is below 0.125%. Immunohistostaining of liver sections with a polyclonal anti-5hmC antibody shows that 5hmC is detected in most of the hepatocytes. Genome-wide mapping of the distribution of 5hmC in human liver samples by next-generation sequencing shows significant differences between fetal and adult livers. In adult livers, 5hmC occupancy is overrepresented in genes involved in active catabolic and metabolic processes, whereas 5hmC elements which are found in genes exclusively in fetal livers and disappear in the adult state, are more specific to pathways for differentiation and development.

Conclusions

Our findings suggest that 5-hydroxymethylcytosine plays an important role in the development and function of the human liver and might be an important determinant for development of liver diseases as well as of the interindividual differences in drug metabolism and toxicity.
The CCN family acting throughout the body: recent research developments
Authors: Kubota Satoshi , Takigawa Masaharu
Published: August 2013

The animal body is composed of a variety of cells and extracellular matrices that are organized and orchestrated in a harmonized manner to support life. Therefore, the critical importance of a comprehensive understanding of the molecular network surrounding and integrating the cells is now emphasized. The CCN family is a novel group of matricellular proteins that interact with and orchestrate a number of extracellular signaling and matrix molecules to construct and maintain living tissues. This family comprises six distinct members in mammals, which are characterized by a unique and conserved modular structure. These proteins are not targeted to limited and specific receptors to execute specific missions, but manipulate a vast number of biomolecules in the network by serving as a molecular hub at the center. The unified nomenclature, CCN, originates from a simple acronym of the three classical members, which helps us to avoid having any preconception about their pleiotropic and anonymous functional nature. In this review, after a brief summary of the general molecular concepts regarding the CCN family, new aspects of each member uncovered by recent research are introduced, which represent, nevertheless, only the tip of the iceberg of the profound functionality of these molecules.
The relationship between oxidative stress and exercise
Authors: Finkler Maya , Lichtenberg Dov , Pinchuk Ilya
Published: August 2013

Physical exercise has many benefits, but it might also have a negative impact on the body, depending on the training level, length of workout, gender, age and fitness. The negative effects of physical exercise are commonly attributed to an imbalance between the levels of antioxidants (both low molecular weight antioxidants and antioxidant enzymes) and reactive oxygen and nitrogen species due to excessive production of free radicals during physical exercise. In this critical review, we look for answers for three specific questions regarding the interrelationship between physical exercise and oxidative stress (OS), namely, (i) the dependence of the steady-state level of OS on fitness, (ii) the effect of intensive exercise on the OS and (iii) the dependence of the effect of the intense exercise on the individual fitness. All these questions have been raised, investigated and answered, but the answers given on the basis of different studies are different. In the present review, we try to explain the reason(s) for the inconsistencies between the conclusions of different investigations, commonly based on the concentrations of specific biomarkers in body fluids. We think that most of the inconsistencies can be attributed to the difference between the criteria of the ill-defined term denoted OS, the methods used to test them and in some cases, between the qualities of the applied assays. On the basis of our interpretation of the differences between different criteria of OS, we consider possible answers to three well-defined questions. Possible partial answers are given, all of which lend strong support to the conclusion that the network responsible for homeostasis of the redox status is very effective. However, much more data are required to address the association between exercise and OS and its dependence on various relevant factors.
Lab-on-a-chip devices for gold nanoparticle synthesis and their role as a catalyst support for continuous flow catalysis
Authors: Navin Chelliah V. , Krishna Katla Sai , Theegala Chandra S. , Kumar Challa S.S.R.
Published: August 2013

Lab-on-a-chip (LOC) systems are extensively used in recent times for applications in nanotechnology ranging from synthesis of nanomaterials to their utilization in catalysis, biomedicine, and drug delivery. A variety of nanomaterials – inorganic materials such as metal, metal oxide, quantum dots, and organic materials based on polymers and biological molecules – have been synthesized and their applications explored based on LOC devices. Among several inorganic nanomaterials, the applications of LOC devices for gold-based nanomaterials have been widely investigated over the past couple of decades. Though the synthesis and applications of inorganic nanomaterials using these systems have been thoroughly reviewed earlier, including those from our group, there are only a few recent review articles that cover gold-based nanomaterials. As the promise of supported gold nanoparticles (NPs) as exceptionally effective catalysts is beginning to be realized, LOC-based approach for continuous flow gold catalysis has begun to be exploited. Here, in this review, we focus on synthesis and catalysis applications of nanostructured gold using the LOC systems. With millifluidics-based LOCs gaining traction, this review fulfills the need for a comprehensive analysis covering both traditional microfluidics as well as recent millifluidics for catalysis applications utilizing gold nanomaterials.
Three-dimensional viscoelastic simulation of the effect of wall slip on encapsulation in the coextrusion process
Authors: Liu Hesheng , Deng Xiaozhen , Huang Yibin , Huang Xingyuan , Li Mengshan
Published: August 2013

A three-dimensional viscoelastic numerical simulation was developed for a two-layer coextrusion through a rectangular channel by using the finite element method. The Phan-Thien and Tanner model was considered as viscoelastic constitutive equations. The generalized Navier’s law was adopted to found the slip boundary condition. The numerical results of the effects of the wall slip coefficient and the flow rate on the interface profile and the degree of encapsulation were compared with the experimental results of previous researchers. It was found that the interfacial offset and the degree of encapsulation increased with the increase of the wall slip coefficient and the flow rate, and the growing rate was large when the wall slip coefficient was between 106 and 108. We were able to control the interface shape and the degree of encapsulation at the die exit by varying the wall slip coefficient and the magnitude of the melt flow rate.
Foraging activity of the snail kite, Rostrhamus sociabilis (Aves: Accipitridae) in wetlands of southern Brazil
Authors: Bergmann FB , Amaral HLC , Pinto DP , Chivittz CC , Tozetti AM
Published: August 2013

The snail kite (Rostrhamus sociabilis) is widely distributed in the American continent. Its specialised diet consists mostly of the gastropod mollusk Pomacea sp and its foraging strategy probably varies depending on the season, prey availability, and climate factors, which can be reflected in its semi-nomad behaviour. This study was aimed at examining the hunting strategy of the snail kite, and its association with climate factors and habitat heterogeneity. Direct observations of birds between January 2010 and March 2011 in southernmost Brazil revealed that hunting was still the predominant foraging strategy (79% of records) to capture mollusks. Despite morphological specialisations to extract mollusks from the shells, the handling time (average = 92.4 s) was twice as much the time between prey search and capture (average = 55 s). The increase in the number of mollusks ingested apparently occurs when the resting time on perches or any other substrates near the hunting sites decreases between successive unsuccessful attempts. The correlation between the number of consumed preys and the climatic variables examined was low. Regarding habitat heterogeneity, our findings suggest that birds forage preferentially in marshes with low vegetation, which may increase the access to mollusks. The hunting efficiency of the snail kite was high (76 % successful attempts) compared to those of other birds of prey.
Effects of recurrent disturbances on the periphyton community downstream of a dammed watercourse
Authors: Zanon JE , Simões NR , Rodrigues L
Published: August 2013

We evaluate experimentally the effect of a sequential disturbance—desiccation—on the structure and dynamics of a periphytic algal community in a semilotic environment of the Upper Paraná River floodplain. We tested the hypothesis that the presence of recurrent disturbances have a direct negative effect on the attributes of the periphyton community. The sequential effect of desiccation on the periphytic community promoted its significant decrease in density, while the same was not observed in species richness. When desiccation was induced in a mature community, there was no difference in the community compared to control. The sequential disturbances on the community of periphytic algae in a mature stage, was characterised by greater stability. It is believed that the effects of variation in water levels caused by upstream reservoirs can likewise also modify the structure and stability of periphytic algae in the Upper Paraná River floodplain.