bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of 9-month angiographic outcomes of Resolute zotarolimus-eluting and everolimus-eluting stents in a real world setting of coronary intervention in Korea
Authors: Lee Joo Myung , Youn Tae-Jin , Park Jin Joo , Oh Il-Young , Yoon Chang-Hwan , Suh Jung-Won , Cho Young-Seok , Cho Goo-Yeong , Chae In-Ho , Choi Dong-Ju
Published: September 2013

Background

Clinical outcomes of new-generation drug-eluting stents (DES), Everolimus-eluting stent (EES) or Resolute zotarolimus-eluting stent (R-ZES), have been reported. However, angiographic follow-up data of new-generation DES are limited, especially in Asians. We investigated the angiographic and clinical outcomes of EES and R-ZES in a real-world setting of Korean patients.

Methods

Angiographic and clinical outcomes of 679 patients (866 lesions) who had been treated with EES or R-ZES from Jun 2008 to May 2010 were evaluated. The primary analysis was to compare in-segment late loss at 9 months and the secondary analyses were to compare the clinical outcomes.

Results

In-segment late loss at 9-month follow-up angiography was 0.23 ± 0.52 mm for EES and 0.29 ± 0.64 mm for R-ZES (p = 0.248). In addition, the rate of binary restenosis did not show between-group differences (5.8%vs.6.8% for EES and R-ZES, respectively, p = 0.716). During a median follow-up of 33 months, there were no significant differences in Kaplan-Meier estimates of target lesion failure (TLF) (7.5% vs. 7.9% for EES and R-ZES, respectively, p = 0.578) and patient-oriented composite outcomes (POCO including all-cause death, any myocardial infarction, and any revascularization, 22.8% vs. 20.1%, p = 0.888). The adjusted hazard ratios for TLF and POCO were 0.875 (95% CI 0.427 - 1.793; p = 0.715) and 1.029 (95% CI 0.642 - 1.650; p = 0.904), respectively, for EES over R-ZES in the propensity score matched group analysis.

Conclusions

In Korean patients undergoing new-generation DES implantation for coronary artery disease, EES and R-ZES showed similar angiographic outcomes at 9 months and comparable clinical outcomes during 2.8 years of median follow-up.
Molecular characterization of T cell receptor beta variable in the peripheral blood T cell repertoire in subjects with active tuberculosis or latent tuberculosis infection
Authors: Yang Jiezuan , He Jianqin , Huang Haijun , Ji Zhongkang , Wei Li , Ye Ping , Xu Kaijin , Li Lanjuan
Published: September 2013

Background

T cells are closely linked to the clinical manifestations of subjects with Mycobacterium tuberculosis (MTB) infection. T cell receptor beta variable (TCRBV) is a signal and indicative molecule on the membrane of T lymphocytes, reflecting the composition and specificity of T cells. The molecular profiles of TCRBV in peripheral blood mononuclear cells (PBMCs) and their subpopulations (CD4+ and CD8+ T cells) from subjects with active tuberculosis (TB) or latent TB infection (LTBI) have not been well described.

Methods

In 42 subjects with active TB or LTBI, PMBCs and their subsets were separated and sorted. The molecular profiles of the TCRBV complementarity determining region 3 (CDR3) in the three cell populations were investigated using our recently developed gene melting spectral pattern (GMSP) assay. The TCRBV members were then cloned and sequenced when their GMSP image profiles showed a single-peak.

Results

The average number of skewed TCRBV molecules in the CD4+ cell subset was significantly higher than that in PBMCs and CD8+ T cells. TCRBV12, BV13.1, BV13.2, and BV24 were expressed more prevalently than other TCRBV gene families in the three cell populations. In addition, relatively conserved amino acid motifs were identified in TCRBV5.1 and BV20 CDR3 in PBMCs and its subsets. The monoclonal TCRBV14 and BV23 expressed were different between active TB and LTBI subjects.

Conclusions

These results indicate that the T cell immune response is complex and multi-specific in active TB and LTBI subjects. Analysis of TCRBV expression in CD4+ T cells suggest that it could be useful in assessing the composition and status of circulating T cells. Furthermore, the expression of TCRBV14, BV23 and the sequencing of CDR3 amino acid motifs of TCRBV5.1, BV20 could be used in the differential diagnosis and treatment of subjects with active TB or LTBI.
Clinical utility of gray scale renal ultrasound in acute kidney injury
Authors: Podoll Amber , Walther Carl , Finkel Kevin
Published: September 2013

Background

Acute kidney injury occurs commonly in hospitalized patients and is associated with significant morbidity and mortality. Although renal ultrasound is often performed, its clinical utility in determining of the cause of acute kidney injury, particularly the detection of urinary tract obstruction, is not established.

Methods

Retrospective cohort study of all adult inpatients that underwent renal ultrasound for acute kidney injury over a 3-year period at a large university teaching hospital. The frequency of renal ultrasound abnormalities and clinical characteristics that predicted the finding of urinary tract obstruction was determined.

Results

Over the 3-year period, 1471 renal ultrasounds were performed of which 55% (810) were for evaluation of acute kidney injury. Renal ultrasound was normal in 62% (500 of 810) of patients. Hydronephrosis was detected in only 5% (42 of 810) of studies and in only 2.3% (19 of 810) of the cases was obstructive uropathy considered the cause of acute kidney injury. The majority of these patients (14 of 19) had a medical history suggestive of urinary tract obstruction. Less than 1% of patients (5 of 810) had urinary tract obstruction on ultrasound without a suggestive medical history. Most other ultrasound findings were incidental and did not establish an etiology for the acute kidney injury.

Conclusions

Renal ultrasound for evaluation of acute kidney injury is indicated if there is medical history suggestive of urinary tract obstruction. Otherwise, renal ultrasound is unlikely to yield useful results and should be used more selectively based on patients’ medical history.
Molecular analysis of a consanguineous Iranian polycystic kidney disease family identifies a PKD2mutation that aids diagnostics
Authors: Vazifehmand Reza , Rossetti Sandro , Saber Sassan , Khorshid Hamid Reza Khorram , Harris Peter C
Published: September 2013

Background

Polycystic kidney diseases (PKD) are a group of monogenic disorders that are inherited dominantly (autosomal dominant PKD; ADPKD) or recessively, including, autosomal recessive PKD (ARPKD). A number of recessive, syndromic disorders also involve PKD but have a range of pleiotropic phenotypes beyond the kidney, and are enriched in consanguineous families.

Case presentation

We describe here a consanguineous Iranian pedigree in which PKD was diagnosed in four generations, but also included cases with additional abnormalities, including mental retardation. We employed molecular screening to reveal the etiology of the PKD. Since the PKD seemed to be dominantly inherited, molecular diagnostics was performed by direct sequencing of the ADPKD genes, PKD1 and PKD2. Clinical and imaging data was collected on family members. The sequence analysis revealed a PKD2 single base-pair deletion, c.1142delG, and segregation was demonstrated in 16 PKD patients from different branches of the family. In keeping with other reports, the PKD2 phenotype in this family was overall mild, and characterized by conserved kidney function, although 12 cases had some evidence of renal insufficiency. Several younger mutation carriers had borderline or no clinical characteristics of ADPKD, while a patient that required a renal transplant at 14 y did not have the PKD2 mutation.

Conclusions

The molecular analysis of an Iranian family showed that the PKD was due to a PKD2 mutation. The identification of the causative mutation allowed an accurate diagnosis in a number of individuals with equivocal imaging data. Consequently, these patients could be followed appropriately as at-risk individuals. In addition, the PKD2 diagnosis ruled out a syndromic form of PKD as the cause of the additional phenotypes in the family.
Recommendation by a law body to ban infant male circumcision has serious worldwide implications for pediatric practice and human rights
Authors: Bates Michael J , Ziegler John B , Kennedy Sean E , Mindel Adrian , Wodak Alex D , Zoloth Laurie S , Tobian Aaron AR , Morris Brian J
Published: September 2013

Background

Recent attempts in the USA and Europe to ban the circumcision of male children have been unsuccessful. Of current concern is a report by the Tasmanian Law Reform Institute (TLRI) recommending that non-therapeutic circumcision be prohibited, with parents and doctors risking criminal sanctions except where the parents have strong religious and ethnic ties to circumcision. The acceptance of this recommendation would create a precedent for legislation elsewhere in the world, thereby posing a threat to pediatric practice, parental responsibilities and freedoms, and public health.

Discussion

The TLRI report ignores the scientific consensus within medical literature about circumcision. It contains legal and ethical arguments that are seriously flawed. Dispassionate ethical arguments and the United Nations Convention on the Rights of the Child are consistent with parents being permitted to authorize circumcision for their male child. Uncritical acceptance of the TLRI report’s recommendations would strengthen and legitimize efforts to ban childhood male circumcision not just in Australia, but in other countries as well. The medical profession should be concerned about any attempt to criminalize a well-accepted and evidence-based medical procedure. The recommendations are illogical, pose potential dangers and seem unworkable in practice. There is no explanation of how the State could impose criminal charges against doctors and parents, nor of how such a punitive apparatus could be structured, nor how strength of ethnic or religious ties could be determined. The proposal could easily be used inappropriately, and discriminates against parents not tied to the religions specified. With time, religious exemptions could subsequently be overturned. The law, governments and the medical profession should reject the TLRI recommendations, especially since the recent affirmative infant male circumcision policy statement by the American Academy of Pediatrics attests to the significant individual and public health benefits and low risk of infant male circumcision.

Doctors should be allowed to perform medical procedures based on sound evidence of effectiveness and safety with guaranteed protection. Parents should be free to act in the best interests of the health of their infant son by having him circumcised should they choose.
Female genital mutilation among Iraqi Kurdish women: a cross-sectional study from Erbil city
Authors: Yasin Berivan A , Al-Tawil Namir G , Shabila Nazar P , Al-Hadithi Tariq S
Published: September 2013

Background

Iraqi Kurdistan region is one of the areas where female genital mutilation is reportedly widely practiced but inadequately studied. The aim of this study was to determine (i) the prevalence of female genital mutilation among Muslim Kurdish women in Erbil city, (ii) the patterns and types of female genital mutilation, (iii) the factors associated with this practice and (iv) women’s knowledge and attitudes towards this practice.

Methods

A cross-sectional study was conducted in the primary health care centers and the Maternity Teaching Hospital in Erbil city, involving 1987 women aged 15–49 years. Data were obtained about female genital mutilation status and knowledge and perception towards this practice. The participants were clinically examined to verify the self-reported female genital mutilation status.

Results

The self-reported prevalence of female genital mutilation was 70.3%, while it was 58.6% according to clinical examination of the women’s genitalia. The most common type of female genital mutilation was type I (99.6%) and the most common age at which mutilation was performed was 4–7 years (60.2%). This practice was mostly performed by traditional birth attendants (72.5%). Only 6.4% of mutilated women reported having complications after mutilation, most commonly bleeding (3.6%). The practice was more reported among housewives (OR = 3.3), those women whose mothers were mutilated (OR = 15.1) or with unknown mutilation status (OR = 7.3) and those women whose fathers were illiterate (OR = 1.4) or could only read and write (OR = 1.6). The common reasons for practicing female genital mutilation were cultural tradition (46.7%) and dictate of religion (38.9%). Only 30% of the participants were aware about the health consequences of female genital mutilation. More than one third (36.6%) of the women support the practice and 34.5% have intention to mutilate their daughters.

Conclusions

Prevalence of female genital mutilation among Muslim Kurdish women in Erbil city is very high; although, most cases are of type I. There is clear lack of knowledge about the health consequences of female genital mutilation and a relatively important segment of women support this practice. Custom or tradition and dictate of religion are the main reasons for this practice that need further in-depth exploration.
The possible impact of an alcohol welfare surcharge on consumption of alcoholic beverages in Taiwan
Authors: Yeh Chun-Yuan , Ho Li-Ming , Lee Jie-Min , Hwang Jhe-Yo
Published: September 2013

Background

The abuse of alcoholic beverages leads to numerous negative consequences in Taiwan, as around the world. Alcohol abuse not only contributes to cardiovascular disease, hypertension, diabetes and cancer, but it is also an underlying cause of many other serious problems, such as traffic accidents, lost productivity, and domestic violence. International leaders in health policy are increasingly using taxation as an effective tool with which to lower alcohol consumption. In this study, we assessed how consumption patterns in Taiwan would be affected by levying a welfare surcharge on alcoholic beverages of 20%, 40% or 60% in accordance with the current excise tax. We also assessed the medical savings Taiwan would experience if consumption of alcoholic beverages were to decrease and how much additional revenue a welfare surcharge would generate.

Methods

We estimated the elasticity of four types of alcoholic beverages (beer, wine, whisky and brandy) using the Central Bureau of Statistics (CBS) Demand Model. Specifically, we estimated alcohol’s price elasticity by analyzing the sales prices and time statistics of these products from 1974 to 2009.

Results

Alcoholic beverages in Taiwan have the following price elasticities: beer (−0.820), wine (−0.955), whisky (−0.587), brandy (−0.958). A welfare surcharge tax of 40% in accordance with the excise tax would decrease overall consumption of beer, wine, whisky and brandy between 16.24% and 16.42%. It would also generate New Taiwan Dollar (NT$) revenues of 5.782 billion to 5.993 billion. Savings in medical costs would range from NT$871.07 million to NT$897.46 million annually.

Conclusions

A social and welfare surcharge of 40% on alcoholic beverages in Taiwan would successfully lower consumption rates, decrease medical costs, and generate revenue that could be used to educate consumers and further decrease consumption rates. Consequently, we strongly recommend that such a tax be imposed in Taiwan.
Surface-associated MUC5B mucins promote protease activity in Lactobacillus fermentum biofilms
Authors: Wickström Claes , Chávez de Paz Luis , Davies Julia R , Svensäter Gunnel
Published: September 2013

Background

Mucosal surfaces are coated with layers of mucus gel that protect the underlying tissues and promote colonization by members of the commensal microflora.Lactobacillus fermentumis a common inhabitant of the oral cavity, gastrointestinal and reproductive tracts and is one of the most important lactic acid bacteria contributing to the formation of a healthy intestinal microflora. We have investigated the proteolytic activity inL. fermentumin response to interactions with the MUC5B mucin, which is a major component of mucus gels at sites colonized by this micro-organism.

Methods

Biofilms ofLactobacillus fermentumwere established in mini-flow cells in the presence or absence of human salivary MUC5B. The proteolytic activity of biofilm cells was examined in a confocal scanning laser microscope with a fluorescent protease substrate. Degradation of MUC5B byL. fermentumwas analysed using SDS-PAGE followed by Western blotting with antisera raised against the MUC5B peptide. Cell surface proteins differentialy expressed in a MUC5B-rich environment were identified with the aid of comparative two-dimensional electrophoresis followed by LC-MS/MS.

Results

Lactobacillus fermentumadhered well to surfaces coated with MUC5B mucin and in biofilms ofL. fermentumformed in a MUC5B environment, the proportion of proteolytically-active cells (47±0.6% of the population), as shown by cleavage of a fluorescent casein substrate, was significantly greater (p<0.01) than that in biofilms formed in nutrient broth (0.4±0.04% of the population). Thus, the presence of MUC5B mucins enhanced bacterial protease activity. This effect was mainly attributable to contact with surface-associated mucins rather than those present in the fluid phase. Biofilms ofL. fermentumwere capable of degrading MUC5B mucins suggesting that this complex glycoprotein can be exploited as a nutrient source by the bacteria.

Comparison of the surface proteomes of biofilm cells ofL. fermentumin a MUC5B environment with those in nutrient broth using two-dimensional electrophoresis and mass spectroscopy, showed that the enhanced proteolytic activity was associated with increased expression of a glycoprotease;O-sialoglycoprotein endopeptidase, as well as chaperone proteins such as DnaK and trigger factor.

Conclusions

Adhesion to mucin-coated surfaces leads to a shift towards a more protease-active phenotype withinL. fermentumbiofilms and proteases produced within the biofilms can degrade MUC5B mucins. The enhanced proteolytic activity was associated with an increase inO-sialoglycoprotein endopeptidase on the cell surface. We propose that the upregulation of chaperone proteins in the mucin environment may contribute to the protease-active phenotype through activation of the glycopeptidase. This would represent one way for commensal lactobacillie.g. L. fermentumto exploit complex substrates in their local environment in order to survive on mucosal surfaces.
The effect of Shenmai injection on the proliferation of Rat airway smooth muscle cells in asthma and underlying mechanism
Authors: Zhao Limin , Wu Jizhen , Zhang Xiaoyu , Kuang Hongyan , Guo Yali , Ma Lijun
Published: September 2013

Background

Over-proliferation of airway smooth muscle cell (ASMC) is one of the important contributors to airway remodeling in asthma. The aim of this study was to investigate the effect of Shenmai injection (SMI) on the proliferation of the rat ASMC in asthma.

Methods

Rats were randomly divided into three groups: the control group, the asthma group, and the SMI treatment group. Reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry staining were used to detect the mRNA and protein expression of transient receptor potential vanilloid 1 (TRPV1) and proliferating cell nuclear antigen (PCNA) in rat ASMC respectively. Intracellular Ca2+ concentration ( [Ca2+]i ) in rat ASMC were measured with Fluo-3/AM by confocal microscopy. The proliferation was detected by MTT assay.

Results

Compared with the control group, the asthma group showed an increased expression of TRPV1 and [Ca2+]i in rat ASMC. The expression of PCNA and absorbance of MTT assay in asthma rat ASMC was also significantly increased. SMI could significantly decrease the expression of TRPV1 channel and [Ca2+]i in the asthmatic rat ASMC. Furthermore, the expression of PCNA and absorbance of MTT assay in asthmatic rat ASMC was significantly reduced after SMI treatment.

Conclusions

SMI may prevent asthma-induced ASMC over-proliferation probably by inhibiting the expression of TRPV1 channel, which regulates the intracellular calcium concentration.
The use of microblog-based case studies in a pharmacotherapy introduction class in China
Authors: Wang Tiansheng , Wang Fei , Shi Luwen
Published: September 2013

Background

Microblog is a Web 2.0 technology that provides an online social networking platform for communicating and sharing information among web users. Pharmacy educators have previously used microblog to promote active engagement of students. However, there is very little research to demonstrate how to use microblogging effectively to enhance pedagogy in a blended or face-to-face classroom environment. We used the most popular microblog website in China to create a “space” within the classroom to evaluate an interactive microblogging forum for the integration of pharmacotherapy case studies. This study is aimed to determine students’ attitudes toward microblog-based case studies (MBC) in a pharmacotherapy class.

Methods

We created a group on Sina Weibo, the most popular microblog website in China, to explore the possibilities of using microblog-based case discussions in pharmacy education to promote and motivate student learning. The class teaching activities began in November 2011; individual group assignments to a single case study were administered to 21 groups with a total of 126 participating pharmacy students. Each group was required to share a discussion care plan on the microblogging platform. Individual students were expected to participate in an online discussion related to at least two other group cases by posting their comments on the microblog platform. All postings were tracked and analyzed, and then a post MBC survey was administered anonymously to determine students’ opinions towards MBC.

Results

A total of 126 students posted 592 messages and 112 students (89%) completed the survey. More than 80% of students agreed that MBC improved communication; nearly 70% agreed that MBC increased the amount of interaction, and over 50% found value in reading other students’ messages. However, 25% students believed the collaborative learning was not effective and 22% indicated the quality of interaction was low.

Conclusions

MBC appears to be well-accepted learning method to students in this study. Educators who wish to use MBC for pharmacy courses should balance the potential advantages, such as improving communication and the amount of interaction, with potential disadvantages, such as inefficient collaborative learning and the low quality of interaction.
Comparison of expression systems for the extracellular production of mannanase Man23 originated from Bacillus subtilis B23
Authors: Zhou Haiyan , Yang Yong , Nie Xu , Yang Wenjiao , Wu Yongyao
Published: September 2013

Background

Mannanase is an enzyme that can catalyze random hydrolysis of beta-1,4-mannosidic linkages in the main chain of mannans, glucomannans and galactomannans which are the key polymers in hemicellulose. It has been used in a number of different industrial applications including food, feed, pharmaceutical, pulp/paper industries, and second generation biofuel. To optimize the expression system of mannanase Man23 gene, two kinds of vectors and host bacteria were determined and compared.

Results

Recombinants pHY-p43-man23 and pBPS-man23 were constructed and transferred into Bacillus subtilis WB600 and Brevibacillus brevis respectively. For mannanase Man23 gene, recombinant pHY-p43-man23 expressed in Brevibacillus brevis had higher production and activity. Compared to the wild-type Bacillus subtilis B23, the production of recombinant pHY-p43-man23 in B. brevis increased by 10 times and activity increased by 21.3%. pHY-p43-man23 in B. brevis had activity at the range of 20 ~ 70°C but its optimum temperature was 50°C and had activity from pH 4 ~ 10 but its optimum pH was around 7. This demonstrated the recombinant had improved stability as well.

Conclusions

Mannanase is an important industrial enzyme and combination of vector pHY-p43 and host Brevibacillus brevis is a novel expression system for a mannanase decoding gene. This work aims at exploring a better expression system of mannanase Man23 decoding gene for industrial application.
Effect of DNA methylation inhibitor on RASSF1A genes expression in non-small cell lung cancer cell line A549 and A549DDP
Authors: Mengxi Duan , Qian Wang , Nan Wang , Xiaoguang Xiao , Shijun Li
Published: September 2013

Background

Ras association domain family 1A gene (RASSFlA) is a candidate suppressor gene, Lack of RASSF1A expression was found in lung cancer. High DNA methylation at the promoter region is the main reason for inactivating RASSF1A transcription.

Methods

In this study, we examined RASSF1A’s methylation status and its mRNA expression level between non-small cell lung cancer cell line A549 and anti-Cisplatin cell strain A549DDP, Furthermore, methylation of A549DDP was reversed by treatment of 5-Aza-2′ - deoxycytidine (5-Aza-cdR),a DNA methyltransferase inhibitor.

Results

We found that RASSF1A’s methylation status and its mRNA expression were obvious differences between A549 and A549DDP. 5-Aza-CdR treatment remarkablly reduced cell vability of A549DDP. Moreover, 5-Aza-CdR treatment induced A549DDP cell apoptosis in a dose dependent manner with declining cell percentage in S and G2/M stage, and increasing proportion in G0/G1 stage. Cell motility was blocked in G0/G1 stage. All of A549DDP cells showed unmethylated expression, its high methylation status was reversed in a dose-dependent manner within a certain range.

Conclusions

The abnormal gene methylation status of RASSF1A is a molecular biomarker in lung cancer diagnosis, treatment and prognosis.
Phenotypic alterations in human saphenous vein culture induced by tumor necrosis factor-alpha and lipoproteins: a preliminary development of an initial atherosclerotic plaque model
Authors: Prasongsukarn Kriengchai , Chaisri Urai , Chartburus Peenutchanee , Wetchabut Kamolwan , Benjathummarak Surachet , Khachansaksumet Vasant , Maneerat Yaowapa
Published: September 2013

Background

Atherosclerosis is a chronic progressive inflammatory disease of blood vessels particularly the arteries. The development of atherosclerotic plaques or atherogenesis is a complex process that is influenced by cardiovascular risk factors such as vascular inflammation and dyslipidemia. This study demonstrates the ability of tumor necrosis factor-alpha (TNF-α) and low density lipoproteins (LDL) to induce atherosclerotic plaque in human saphenous vein (HSV) organ culture.

Methods

Normal HSV segments, from male patients who had coronary bypass graft, were cultured in DMEM containing 5% heat inactivated fetal bovine serum. TNF-α (5 ng/ml) was applied in combination with native LDL (nLDL) or oxidized LDL (oxLDL) at the dose of 50 μg/ml for 14 days. The phenotypic changes of the organ cultures characteristic of initial atherosclerotic plaques were evaluated. The effect of anti-atherogenic agent, 17-β estradiol (E2), was also determined.

Results

Histologic, histomorphometric, and immunohistochemical examinations revealed that HSV rings stimulated with TNF-α + nLDL or TNF-α + oxLDL can exhibit the essential morphological features of atherogenesis, including fibrous cap formation, cholesterol clefts, evident thickening of the intimal layer, increased proliferation of smooth muscle cells (SMC) and migration to the subendothelial layer, significant SMC foam cell formation, and increased expression of adhesion molecules in the vascular wall. Addition of E2 (50 nM) to the culture significantly modulated the critical changes. Consistently, mRNA profiling of the HSV model revealed that 50 of 84 genes of atherosclerosis were up-regulated.

Conclusions

Phenotypic changes characteristic of the initial development of atherosclerotic plaques can be induced in HSV organ culture.
Biological constraints limit the use of rapamycin-inducible FKBP12-Inp54p for depleting PIP2 in dorsal root ganglia neurons
Authors: Coutinho-Budd Jaeda C , Snider Samuel B , Fitzpatrick Brendan J , Rittiner Joseph E , Zylka Mark J
Published: September 2013

Background

Rapamycin-induced translocation systems can be used to manipulate biological processes with precise temporal control. These systems are based on rapamycin-induced dimerization of FK506 Binding Protein 12 (FKBP12) with the FKBP Rapamycin Binding (FRB) domain of mammalian target of rapamycin (mTOR). Here, we sought to adapt a rapamycin-inducible phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phosphatase (Inp54p) system to deplete PIP2 in nociceptive dorsal root ganglia (DRG) neurons.

Results

We genetically targeted membrane-tethered CFP-FRBPLF (a destabilized FRB mutant) to the ubiquitously expressed Rosa26 locus, generating a Rosa26-FRBPLF knockin mouse. In a second knockin mouse line, we targeted Venus-FKBP12-Inp54p to the Calcitonin gene-related peptide-alpha (CGRPα) locus. We hypothesized that after intercrossing these mice, rapamycin treatment would induce translocation of Venus-FKBP12-Inp54p to the plasma membrane in CGRP+ DRG neurons. In control experiments with cell lines, rapamycin induced translocation of Venus-FKBP12-Inp54p to the plasma membrane, and subsequent depletion of PIP2, as measured with a PIP2 biosensor. However, rapamycin did not induce translocation of Venus-FKBP12-Inp54p to the plasma membrane in FRBPLF-expressing DRG neurons (in vitro or in vivo). Moreover, rapamycin treatment did not alter PIP2-dependent thermosensation in vivo. Instead, rapamycin treatment stabilized FRBPLF in cultured DRG neurons, suggesting that rapamycin promoted dimerization of FRBPLF with endogenous FKBP12.

Conclusions

Taken together, our data indicate that these knockin mice cannot be used to inducibly deplete PIP2 in DRG neurons. Moreover, our data suggest that high levels of endogenous FKBP12 could compete for binding to FRBPLF, hence limiting the use of rapamycin-inducible systems to cells with low levels of endogenous FKBP12.
Solitary intracranial osteoma with attachment to the falx: a case report
Authors: Chen Shu-Mei , Chuang Chi-Cheng , Toh Cheng-Hong , Jung Shih-Ming , Lui Tai-Ngar
Published: September 2013

Background

Intracranial osteomas are uncommon lesions that usually arise from the inner table of the cranium. There are few reports in the literature of intracranial osteomas with meninges attachment and without direct relation with the skull bone; these osteomas were mostly attached with dura. We report a rare osteoma with falx attachment.

Case

A 64-year-old woman presented with a 3-month history of intermittent tinnitus and dizziness. The scout film of petrous bone computed tomography scan revealed a high-density lesion in the frontal area. Magnetic resonance imaging showed a 2.5-cm mass attached to the surface of the falx in the right frontal parasagittal area. The patient underwent right frontal craniotomy, and a bony hard mass was found located in the right frontal parasagittal region extra-axially, with its medial surface attached to the falx. It could not be broken down by the cavitron ultrasonic surgical aspirator or even the cutting loop and was detached from the falx and removed in one piece. Histopathological examination showed a nodule with bony trabeculae and bone marrow tissue, compatible with osteoma. The postoperative course was uneventful, and the patient was discharged from the hospital with no neurological deficits one week after operation.

Conclusions

This is the first case report in the English literature of an intracranial osteoma arising from the falx. Because of their slow growth and their locations in silent brain areas, intracranial osteomas are usually diagnosed incidentally. Surgical resection is the primary treatment choice.
Vitamin D deficiency and prognostics among patients with pancreatic adenocarcinoma
Authors: Cho May , Peddi Parvin F , Ding Kevin , Chen Ling , Thomas Denise , Wang Jian , Lockhart Albert C , Tan Benjamin , Wang-Gillam Andrea
Published: September 2013

Background

The prevalence of vitamin D deficiency among patients with cancer has been previously reported. Because vitamin D is fat soluble, patients with pancreatic adenocarcinoma may have an especially high risk of vitamin D deficiency in association with ongoing and varying degrees of malabsorption. However, little is known about the correlation between vitamin D status and prognosis in these patients.

Methods

We conducted a retrospective review of vitamin D status in patients with pancreatic adenocarcinoma who were treated at Siteman Cancer Center. Patients’ demographic information, clinical staging at the time of vitamin D assessment, vitamin D levels, and survival data were collected. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25[OH]D) level of less than 20 ng/mL, and vitamin D insufficiency was defined as a 25(OH)D level of between 20 ng/mL and 30 ng/mL.

Results

Between December 2007 and June 2011, 178 patients with pancreatic adenocarcinoma had their vitamin D levels checked at the time of initial visit at this center. Of these 178 patients, 87 (49%) had vitamin D deficiency, and 44 (25%) had vitamin D insufficiency. The median 25(OH)D level was significantly lower among nonwhite patients and among patients with stage I and II disease. A 25(OH)D level of less than 20 ng/mL was found to be associated with poor prognosis (p = 0.0019) in patients with stage III and IV disease.

Conclusions

Vitamin D insufficiency and deficiency were prevalent among patients with pancreatic adenocarcinoma. The vitamin D level appears to be prognostic for patients with advanced pancreatic adenocarcinoma, and its effects should be further examined in a prospective study.
Cone-like graphene nanostructures: electronic and optical properties
Authors: Ulloa Pablo , Latgé Andrea , Oliveira Luiz E , Pacheco Monica
Published: September 2013

A theoretical study of electronic and optical properties of graphene nanodisks and nanocones is presented within the framework of a tight-binding scheme. The electronic densities of states and absorption coefficients are calculated for such structures with different sizes and topologies. A discrete position approximation is used to describe the electronic states taking into account the effect of the overlap integral to first order. For small finite systems, both total and local densities of states depend sensitively on the number of atoms and characteristic geometry of the structures. Results for the local densities of charge reveal a finite charge distribution around some atoms at the apices and borders of the cone structures. For structures with more than 5,000 atoms, the contribution to the total density of states near the Fermi level essentially comes from states localized at the edges. For other energies, the average density of states exhibits similar features to the case of a graphene lattice. Results for the absorption spectra of nanocones show a peculiar dependence on the photon polarization in the infrared range for all investigated structures.
Complexities of gender assignment in 17β-hydroxysteroid dehydrogenase type 3 deficiency: is there a role for early orchiectomy?
Authors: Chuang Janet , Vallerie Amy , Breech Lesley , Saal Howard M , Alam Shumyle , Crawford Peggy , Rutter Meilan M
Published: September 2013

Background

17β-Hydroxysteroid dehydrogenase type-3 (17βHSD-3) deficiency is a rare cause of 46,XY disorders of sex development. The enzyme converts androstenedione to testosterone, necessary for masculinization of male genitalia in utero. 17βHSD-3 deficiency is frequently diagnosed late, at puberty, following virilization, with consequent female-to-male gender reassignment in 39-64%. The decision for sex of rearing is difficult, especially if diagnosed in early childhood. Consensus guidelines are equivocal or support male gender assignment. Long-term outcomes data to guide decisions are also lacking; however, in the few cases of early diagnosis and orchiectomy, female gender retention appears more likely.

We report two patients with 17βHSD-3 deficiency, who presented at unusual ages, in whom female gender was chosen. We performed a focused literature review and summary of gender outcomes in 17βHSD-3 deficiency following early orchiectomy.

Cases

Patient A was a phenotypic female who presented at one year of age with bilateral inguinal hernias and external female genitalia. Testes were identified at surgery. The karyotype was 46,XY. She was initially diagnosed with complete androgen insensitivity syndrome; however, androgen receptor mutation analysis was negative. Human chorionic gonadotropin stimulation yielded a low testosterone: androstenedione ratio (0.6, normal >0.8). Genetic testing demonstrated compound heterozygosity for two known mutations of the HSD17B3 gene. She underwent bilateral orchiectomy at two years of age.

Patient B was born with female genitalia and virilized at 13 years of age. She did not seek evaluation until 22 years of age. Her karyotype was 46,XY. She had bilateral inguinal testes and low testosterone: androstenedione ratio (0.3). HSD17B3 gene sequencing showed her to be a compound heterozygote for two known mutations. She identified herself as female and underwent bilateral orchiectomy and estrogen replacement therapy.

Conclusions

These two patients highlight the complexities of diagnosis and management in 17βHSD-3 deficiency. Although existing data are limited, early orchiectomy is likely to result in retention of female gender identity, avoiding the complications related to virilization in adolescence. As such, it is important to pursue a definitive diagnosis to guide clinical decisions, and to have the support and long term follow up with an inter-disciplinary disorders of sex development team.
Peanut Allergen Threshold Study (PATS): validation of eliciting doses using a novel single-dose challenge protocol
Authors: Zurzolo Giovanni A , Allen Katrina J , Taylor Steve L , Shreffler Wayne G , Baumert Joseph L , Tang Mimi L K , Gurrin Lyle C , Mathai Michael L , Nordlee Julie A , DunnGalvin Audrey , Hourihane Jonathan O’B
Published: September 2013

Background

The eliciting dose (ED) for a peanut allergic reaction in 5% of the peanut allergic population, the ED05, is 1.5 mg of peanut protein. This ED05 was derived from oral food challenges (OFC) that use graded, incremental doses administered at fixed time intervals. Individual patients’ threshold doses were used to generate population dose-distribution curves using probability distributions from which the ED05 was then determined. It is important to clinically validate that this dose is predictive of the allergenic response in a further unselected group of peanut-allergic individuals.

Methods/Aims

This is a multi-centre study involving three national level referral and teaching centres. (Cork University Hospital, Ireland, Royal Children’s Hospital Melbourne, Australia and Massachusetts General Hospital, Boston, U.S.A.) The study is now in process and will continue to run until all centres have recruited 125 participates in each respective centre.

A total of 375 participants, aged 1–18 years will be recruited during routine Allergy appointments in the centres. The aim is to assess the precision of the predicted ED05 using a single dose (6 mg peanut = 1.5 mg of peanut protein) in the form of a cookie. Validated Food Allergy related Quality of Life Questionnaires-(FAQLQ) will be self-administered prior to OFC and 1 month after challenge to assess the impact of a single dose OFC on FAQL. Serological and cell based in vitro studies will be performed.

Conclusion

The validation of the ED05 threshold for allergic reactions in peanut allergic subjects has potential value for public health measures. The single dose OFC, based upon the statistical dose-distribution analysis of past challenge trials, promises an efficient approach to identify the most highly sensitive patients within any given food-allergic population.
Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial
Authors: Bucur Roxana C , Reid Lauren S , Hamilton Celeste J , Cummings Steven R , Jamal Sophie A
Published: September 2013

Background

Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study.

Methods and design

This will be an open-label randomized, controlled trial conducted at Women’s College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the ‘multiple comparisons with the best’ approach for data analyses, as this strategy allows practical considerations of ease of use and tolerability to guide selection of the preparation for future studies.

Discussion

Data from this protocol will be used to develop a randomized, controlled trial of nitrates to prevent osteoporotic fractures.

Trial registration

ClinicalTrials.gov Identifier: NCT01387672. Controlled-Trials.com: ISRCTN08860742.
A realist review of interventions and strategies to promote evidence-informed healthcare: a focus on change agency
Authors: McCormack Brendan , Rycroft-Malone Joanne , DeCorby Kara , Hutchinson Alison M , Bucknall Tracey , Kent Bridie , Schultz Alyce , Snelgrove-Clarke Erna , Stetler Cheyl , Titler Marita , Wallin Lars , Wilson Valerie
Published: September 2013

Background

Change agency in its various forms is one intervention aimed at improving the effectiveness of the uptake of evidence. Facilitators, knowledge brokers and opinion leaders are examples of change agency strategies used to promote knowledge utilization. This review adopts a realist approach and addresses the following question: What change agency characteristics work, for whom do they work, in what circumstances and why?

Methods

The literature reviewed spanned the period 1997-2007. Change agency was operationalized as roles that are aimed at effecting successful change in individuals and organizations. A theoretical framework, developed through stakeholder consultation formed the basis for a search for relevant literature. Team members, working in sub groups, independently themed the data and developed chains of inference to form a series of hypotheses regarding change agency and the role of change agency in knowledge use.

Results

24, 478 electronic references were initially returned from search strategies. Preliminary screening of the article titles reduced the list of potentially relevant papers to 196. A review of full document versions of potentially relevant papers resulted in a final list of 52 papers. The findings add to the knowledge of change agency as they raise issues pertaining to how change agents’ function, how individual change agent characteristics effect evidence-informed health care, the influence of interaction between the change agent and the setting and the overall effect of change agency on knowledge utilization. Particular issues are raised such as how accessibility of the change agent, their cultural compatibility and their attitude mediate overall effectiveness. Findings also indicate the importance of promoting reflection on practice and role modeling. The findings of this study are limited by the complexity and diversity of the change agency literature, poor indexing of literature and a lack of theory-driven approaches.

Conclusion

This is the first realist review of change agency. Though effectiveness evidence is weak, change agent roles are evolving, as is the literature, which requires more detailed description of interventions, outcomes measures, the context, intensity, and levels at which interventions are implemented in order to understand how change agent interventions effect evidence-informed health care.
Phase II randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases
Authors: Rojas-Puentes Luis L , Gonzalez-Pinedo Marcelino , Crismatt Alejando , Ortega-Gomez Alette , Gamboa-Vignolle Carlos , Nuñez-Gomez Rodrigo , Dorantes-Gallareta Yusmiren , Arce-Salinas Claudia , Arrieta Oscar
Published: September 2013

Background and purpose

Chloroquine (CLQ), an antimalarial drug, has a lysosomotropic effect associated with increased radiationsensibility, which is mediated by the leakage of hydrolytic enzymes, increased apoptosis, autophagy and increased oxidative stress in vitro. In this phase II study, we evaluated the efficacy and safety of radiosensibilization using CLQ concomitant with 30 Gray (Gy) of whole-brain irradiation (WBI) to treat patients with brain metastases (BM) from solid tumors.

Methods

Seventy-three eligible patients were randomized. Thirty-nine patients received WBI (30 Gy in 10 fractions over 2 weeks) concomitant with 150 mg of CLQ for 4 weeks (the CLQ arm). Thirty-four patients received the same schedule of WBI concomitant with a placebo for 4 weeks (the control arm). All the patients were evaluated for quality of life (QoL) using the EORTC Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) (Mexican version) before beginning radiotherapy and one month later.

Results

The overall response rate (ORR) was 54% for the CLQ arm and 55% for the control arm (p=0.92). The progression-free survival of brain metastases (BMPFS) rates at one year were 83.9% (95% CI 69.4-98.4) for the CLQ arm and 55.1% (95% CI 33.6-77.6) for the control arm. Treatment with CLQ was independently associated with increased BMPFS (RR 0.31,95% CI [0.1-0.9], p=0.046).The only factor that was independently associated with increased overall survival (OS) was the presence of< 4 brain metastases (RR 1.9, 95% CI [1.12-3.3], p=0.017). WBI was associated with improvements in cognitive and emotional function but also with worsened nausea in both patients groups. No differences in QoL or toxicity were found between the study arms.

Conclusion

Treatment with CLQ plus WBI improved the control of BM (compared with the control arm) with no increase in toxicity; however, CLQ did not improve the RR or OS. A phase III clinical trial is warranted to confirm these findings.