bluuebunny/crossref_metadata_2025 huggingface dataset:
Demystifying Mixers
Authors: Thompson Douglas Earl
Published: August 2012

Using music technology is a daily reality for music educators. The task may be as simple as readying a CD player for use in an elementary classroom or as complex as setting up a complete sound system—including microphones, mixer, amplifier, and speakers—for a live music production. One piece of music technology music educators constantly encounter is the audio mixer, usually referred to as “mixer.” Mixers, found everywhere sound is recorded or reproduced, are vital to the sound recording and reproduction process. Yet few teachers are prepared for making more than rudimentary sense of the mixer’s multiple knobs, buttons, and sliders. In this column, a framework is provided for understanding how music educators can better understand mixers by describing a mixer’s essential sections: the input, channel strip, buss, and output sections. This article also offers tips to better enable educators to use mixers.
Human Rights Engagement and Exposure
Authors: McPherson Jane , Abell Neil
Published: August 2012

Objectives: Advancing human rights is a core competency of U.S. social work education; yet, human rights attitudes and behaviors have never been measured in the social work literature. Thus, this article describes the development and initial validation of two scales, Human Rights Engagement in Social Work (HRESW) and Human Rights Exposure in Social Work (HRXSW). Method: The scales were validated using a purposive sample of 287 social work students. Results: Factor analysis supported a 25-item HRESW and an independent 11-item HRXSW. Reliability was assessed: HRESW (α = .894) and HRXSW (α = .734). Conclusions: The HRESW and the HRXSW have direct applicability to social work education. Through measuring exposure and engagement, we can begin assessing the quality of human rights education in social work.
Promoting Successful Aging Through Competitive Sports Participation
Authors: Heo Jinmoo , Culp Brian , Yamada Naoko , Won Youngshin
Published: August 2012

In this study we explored the experience of competing in the Senior Games and the resultant contributions to the successful aging of older adults. We used in-depth interviews with older adults who participated in the National Senior Games. Analysis of the data produced five central themes: (a) perseverance, (b) career development and significant effort, (c) personal and social benefits, (d) unique ethos, and (e) identification as a senior athlete. We found that participating in the Senior Games as a form of serious leisure enhanced the well-being of older adults and could be utilized as a means by which to maintain a healthy lifestyle.
Telmisartan Prevents Excess-Salt-Induced Exacerbated (Malignant) Hypertension in Spontaneously Hypertensive Rats
Authors: Susic Dinko , Fares Hassan , Frohlich Edward D.
Published: August 2012

The effects of angiotensin receptor blocker, diuretic, a calcium antagonist, and their combination were evaluated on the progression of cardiovascular and renal damage in spontaneously hypertensive rats (SHRs) given excess salt. To this end, 8-week male SHRs were divided into 7 groups. The control group (C) received normal NaCl (0.6%) diet. All other groups were given 8% NaCl rat chow. In addition, group 2 was given placebo (tap water alone), group 3 the angiotensin receptor antagonist telmisartan (10 mg/kg per d), group 4 received the diuretic chlorothiazide (80 mg/kg per d), group 5 was given telmisartan plus the diuretic, group 6 was given the calcium antagonist amlodipine (10 mg/kg per d), and group 7 was given telmisartan plus amlodipine. All treatments lasted for 8 weeks. Compared with controls, mean arterial pressure (MAP), renal blood flow, coronary flow reserve, minimal coronary vascular resistance, diastolic time constant, and maximal rate of ventricular pressure fall were all adversely affected by salt loading. Increased left ventricular mass with marked cardiac fibrosis was also found in the salt-overloaded SHR group. Telmisartan normalized all indices except MAP, whereas diuretic and amlodipine only partially restored cardiac functional and mass indexes. Combination therapy with telmisartan and either diuretic or amlodipine also normalized all indices including arterial pressure. These data suggest that (1) cardiovascular  damage induced by excess salt in the SHRs was not pressure dependent; (2) compared with the calcium antagonist and diuretic, blockade of angiotensin receptors  was extremely effective in this model.
The US Military Experience With Fresh Whole Blood During the Conflicts in Iraq and Afghanistan
Authors: Chandler Mark H. , Roberts Matthew , Sawyer Mike , Myers Greg
Published: August 2012

Since its introduction in the early part of the last century, fresh whole blood (FWB) has been used by the US military as a battlefield expedient resuscitation method, even after the development of component therapy in the 1960s. In the recent conflicts in Iraq and Afghanistan, FWB was used once more, often collected in the setting of a walking blood bank (WBB). Considerable research and opinion from military circles has cited these experiences and sparked renewed interest in FWB as an effective resuscitation tool in the setting of trauma. Despite efforts by the US military to improve the effectiveness and safety of FWB through a series of widely published guidelines, transfusion transmitted infections (TTI) remain a vexing challenge. These experiences in Iraq and Afghanistan will help inform a larger discussion regarding the reintroduction of FWB in civilian trauma resuscitation.
A search for specificity in understanding CA and context
Authors: Waring Hansun Zhang , Creider Sarah , Tarpey Tara , Black Rebecca
Published: August 2012

The conversation analytic view of context is often critiqued as being too narrow. In this article, we join the ongoing debate regarding conversation analysis (CA) and context by 1) synthesizing existing scholarly attempts at either conceptualizing or exploring the possibilities of combining CA and ethnography and 2) giving further considerations to whether or how resorting to talk-extrinsic data may be beneficial. We do so by providing four illustrative cases, with increasing complexity, from four different settings. In each case, an initial CA analysis is followed up with an informal ethnographic interview with the participants. By offering some specificity to this ongoing methodological controversy regarding talk-extrinsic data, we aim to begin building a useful framework within which further discussions on analysis, context, and cross-fertilization may proceed.
Thalidomide-Associated Thrombosis in the Treatment of HIV-Associated Severe Aphthous Disease
Authors: Hodowanec Aimee C. , Han Alice , Barker David E. , Rubinstein Paul G. , Max Blake
Published: August 2012

Venous thrombosis is a well-described complication of thalidomide therapy in patients with multiple myeloma (MM). However, an association between thalidomide use and thrombosis in HIV-positive patients has not been previously described. We present the case of a 48-year-old HIV-positive man who developed a deep venous thrombosis while on thalidomide for the treatment of severe aphthous ulcers. We review the management of severe aphthous disease and the potential adverse effects of thalidomide therapy. We examine the association between thalidomide and thrombosis in patients with MM and discuss how the same relationship may or may not exist in HIV-positive patients. Although the strength of the association between thalidomide use and thrombosis in HIV-positive patients being treated for aphthous disease remains unclear, HIV providers should be aware of the potential risk of thrombosis in all patients receiving thalidomide.
Once-Daily Nevirapine XR
Authors: Bhatti Laveeza , Gladstein Jay
Published: August 2012

Nevirapine (NVP) was the first nonnucleoside reverse transcriptase inhibitor (NNRTI) approved by the US Food and Drug Administration (FDA) in 1996, for the treatment of HIV infection. Current treatment guidelines include NVP as a component of a recommended alternative NNRTI regimen, which may be the preferred regimen for patients with established cardiovascular risk factors since NVP has minimal untoward effects on serum lipids. Two randomized and controlled clinical trials established the noninferior virologic efficacy of twice-daily NVP versus ritonavir-boosted atazanavir (ATV/r), a protease inhibitor with limited effects on serum lipids, each drug on a background regimen of once-daily (QD) tenofovir (TDF)/emtricitabine (FTC). An extended-release (XR) formulation of NVP was developed since QD dosing and reduced pill burdens have been shown to improve regimen adherence. This formulation (Viramune XR 400 mg) was recently FDA approved based on the results of 2 randomized, controlled clinical trials. The XR formulation will provide additional treatment options for patients who may benefit from NVP-based regimens.
Processing of Al/304 stainless steel composite by roll bonding
Authors: Tayyebi M , Eghbali B
Published: August 2012

In the present study, a new technique, mesh reinforcing by roll bonding (MRRB), is proposed to manufacture metal matrix composites. An aluminium matrix composite reinforced with 304 stainless steel (304SS) mesh was fabricated via the MRRB process. Structure and mechanical properties of these composites were studied within different stages of the MRRB process. Tensile tests were used to evaluate the mechanical properties of the MRRB processed 304SS/Al composites. Microstructural studies show that passes of MRRB that preceded 304SS meshes were necked and fractured. After four cycles of MRRB, an aluminium matrix composite with excellent distribution of two different types of 304SS particles was achieved. It reveals that the strength and elongation of these composites increase with increasing MRRB cycles. The tensile strength of the Al/304SS composite becomes ∼3·6 times greater than that of the annealed aluminium used as the starting material.
Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjögren syndrome
Authors: Xu Junji , Wang Dandan , Liu Dayong , Fan Zhipeng , Zhang Huayong , Liu Ousheng , Ding Gang , Gao Runtao , Zhang Chunmei , Ding Yaozhong , Bromberg Jonathan S. , Chen Wanjun , Sun Lingyun , Wang Songlin
Published: August 2012

Sjögren syndrome (SS) is a systemic autoimmune disease characterized by dry mouth and eyes, and the cellular and molecular mechanisms for its pathogenesis are complex. Here we reveal, for the first time, that bone marrow mesenchymal stem cells in SS-like NOD/Ltj mice and human patients were defective in immunoregulatory functions. Importantly, treatment with mesenchymal stem cells (MSCs) suppressed autoimmunity and restored salivary gland secretory function in both mouse models and SS patients. MSC treatment directed T cells toward Treg and Th2, while suppressing Th17 and Tfh responses, and alleviated disease symptoms. Infused MSCs migrated toward the inflammatory regions in a stromal cell–derived factor-1–dependent manner, as neutralization of stromal cell–derived factor-1 ligand CXCR4 abolished the effectiveness of bone marrow mesenchymal stem cell treatment. Collectively, our study suggests that immunologic regulatory functions of MSCs play an important role in SS pathogenesis, and allogeneic MSC treatment may provide a novel, effective, and safe therapy for patients with SS. This study was registered at www.clinicaltrials.gov as NCT00953485.
Loss of p53 accelerates the complications of myelodysplastic syndrome in a NUP98-HOXD13–driven mouse model
Authors: Xu Haiming , Menendez Silvia , Schlegelberger Brigitte , Bae Narae , Aplan Peter D. , Göhring Gudrun , Deblasio Tony R. , Nimer Stephen D.
Published: August 2012

The nucleoporin gene NUP98 is fused to several genes including HOXD13 in patients with myelodysplastic syndromes (MDS), acute myeloid leukemia, and chronic myeloid leukemia, blast crisis. Genetically engineered mice that express a NUP98-HOXD13 (NHD13) transgene (Tg) display the phenotypic features of MDS, including cytopenias, bone marrow dysplasia, and transformation to acute leukemia. Here we show that short-term treatment with the p53 inhibitor Pifithrin-α partially and transiently rescued the myeloid and lymphoid abnormalities found in NHD13+ Tg mice, with no improvement in the anemia, while the genetic deletion of 2 alleles of p53 rescued both the myeloid progenitor cell and long-term hematopoietic stem cell compartments. Nonetheless, loss of one or both alleles of p53 did not rescue the MDS phenotype, but instead exacerbated the MDS phenotype and accelerated the development of acute myeloid leukemia. Our studies suggest that while targeting p53 may transiently improve hematopoiesis in MDS, over the long-term, it has detrimental effects, raising caution about abrogating its function to treat the cytopenias that accompany this disease.
Process attributes in bio-ontologies
Authors: Andrade André Q , Blondé Ward , Hastings Janna , Schulz Stefan
Published: August 2012

Background

Biomedical processes can provide essential information about the (mal-) functioning of an organism and are thus frequently represented in biomedical terminologies and ontologies, including the GO Biological Process branch. These processes often need to be described and categorised in terms of their attributes, such as rates or regularities. The adequate representation of such process attributes has been a contentious issue in bio-ontologies recently; and domain ontologies have correspondingly developed ad hoc workarounds that compromise interoperability and logical consistency.

Results

We present a design pattern for the representation of process attributes that is compatible with upper ontology frameworks such as BFO and BioTop. Our solution rests on two key tenets: firstly, that many of the sorts of process attributes which are biomedically interesting can be characterised by the ways that repeated parts of such processes constitute, in combination, an overall process; secondly, that entities for which a full logical definition can be assigned do not need to be treated as primitive within a formal ontology framework. We apply this approach to the challenge of modelling and automatically classifying examples of normal and abnormal rates and patterns of heart beating processes, and discuss the expressivity required in the underlying ontology representation language. We provide full definitions for process attributes at increasing levels of domain complexity.

Conclusions

We show that a logical definition of process attributes is feasible, though limited by the expressivity of DL languages so that the creation of primitives is still necessary. This finding may endorse current formal upper-ontology frameworks as a way of ensuring consistency, interoperability and clarity.
Indehiscent sporangia enable the accumulation of local fern diversity at the Qinghai-Tibetan Plateau
Authors: Wang Li , Schneider Harald , Wu Zhiqiang , He Lijuan , Zhang Xianchun , Xiang Qiaoping
Published: August 2012

Background

Indehiscent sporangia are reported for only a few of derived leptosporangiate ferns. Their evolution has been likely caused by conditions in which promotion of self-fertilization is an evolutionary advantageous strategy such as the colonization of isolated regions and responds to stressful habitat conditions. The Lepisorus clathratus complex provides the opportunity to test this hypothesis because these derived ferns include specimens with regular dehiscent and irregular indehiscent sporangia. The latter occurs preferably in well-defined regions in the Himalaya. Previous studies have shown evidence for multiple origins of indehiscent sporangia and the persistence of populations with indehiscent sporangia at extreme altitudinal ranges of the Qinghai-Tibetan Plateau (QTP).

Results

Independent phylogenetic relationships reconstructed using DNA sequences of the uniparentally inherited chloroplast genome and two low-copy nuclear genes confirmed the hypothesis of multiple origins of indehiscent sporangia and the restriction of particular haplotypes to indehiscent sporangia populations in the Lhasa and Nyingchi regions of the QTP. In contrast, the Hengduan Mountains were characterized by high haplotype diversity and the occurrence of accessions with and without indehiscent sporangia. Evidence was found for polyploidy and reticulate evolution in this complex. The putative case of chloroplast capture in the Nyingchi populations provided further evidence for the promotion of isolated but persistent populations by indehiscent sporangia.

Conclusions

The presented results confirmed the hypothesis that indehiscent sporangia promote the establishment of persistent population in different regions of the QTP. These results are consistent with the expectations of reproductive reassurance by promotion of self-fertilization that played a critical role in the assembly of populations in isolated locations and/or extreme habitats.
Waved with open eyelids 2 (woe2) is a novel spontaneous mouse mutation in the protein phosphatase 1, regulatory (inhibitor) subunit 13 like (Ppp1r13l)gene
Authors: Toonen Joseph , Liang Lina , Sidjanin Duska J
Published: August 2012

Background

Waved with open eyelids 2 (woe2) is a novel autosomal recessive mouse mutation that arose spontaneously in our animal facility. Upon initial evaluation, mutant mice exhibited eyelids open at birth (EOB) and wavy fur phenotypes. The goals of this study were to phenotypically characterize the woe2 mice and to identify the gene harboring the mutation responsible for the woe2 phenotype.

Results

Histological analysis of woe2 embryos identified the failure of embryonic eyelid closure. Clinical and histological analysis of woe2 adult eyes identified severe corneal opacities, abnormalities of the anterior segment of the eye, and the absence of meibomian glands. Abnormalities in the fur texture and the absence of meibomian glands prompted us to evaluate other epidermal appendages: skin, teeth, and nails--as well as lacrimal, mammary, salivary, sebaceous and sweat glands. No obvious morphological differences between WT and woe2 mice were identified in these tissues. However, the analysis of woe2 identified cardiac abnormalities. Positional cloning of the woe2 locus identified a 1308 bp deletion in the Ppp1r13l gene. The deletion resulted in an aberrant Ppp1r13l

Δexon9-11
transcript that lacks exons 9, 10 and 11 resulting in a premature stop and a loss of 223 amino acids from the C-terminal end of the putative mutant PPP1R13L protein. Immunohistological analysis during eye development identified expression of PPP1R13L in the palpebral epidermis, palpebral and bulbar conjunctiva, corneal epithelium and meibomian glands.

Conclusions

The woe2 mouse harbors a novel deletion within the Ppp1r13l gene, likely resulting in a complete loss of PPP1R13L function. Results from this study provide evidence that PPP1R13L has an essential role in embryonic eyelid closure as well in development of meibomian glands and the anterior segment of the eye. The woe2 mice are a useful model for investigation of the role of PPP1R13L, especially during ocular and eyelid development.
Chromosomal differences between European and North American Atlantic salmon discovered by linkage mapping and supported by fluorescence in situ hybridization analysis
Authors: Brenna-Hansen Silje , Li Jieying , Kent Matthew P , Boulding Elizabeth G , Dominik Sonja , Davidson William S , Lien Sigbjørn
Published: August 2012

Background

Geographical isolation has generated a distinct difference between Atlantic salmon of European and North American Atlantic origin. The European Atlantic salmon generally has 29 pairs of chromosomes and 74 chromosome arms whereas it has been reported that the North American Atlantic salmon has 27 chromosome pairs and an NF of 72. In order to predict the major chromosomal rearrangements causing these differences, we constructed a dense linkage map for Atlantic salmon of North American origin and compared it with the well-developed map for European Atlantic salmon.

Results

The presented male and female genetic maps for the North American subspecies of Atlantic salmon, contains 3,662 SNPs located on 27 linkage groups. The total lengths of the female and male linkage maps were 2,153 cM and 968 cM respectively, with males characteristically showing recombination only at the telomeres. We compared these maps with recently published SNP maps from European Atlantic salmon, and predicted three chromosomal reorganization events that we then tested using fluorescence in situ hybridization (FISH) analysis. The proposed rearrangements, which define the differences in the karyotypes of the North American Atlantic salmon relative to the European Atlantic salmon, include the translocation of the p arm of ssa01 to ssa23 and polymorphic fusions: ssa26 with ssa28, and ssa08 with ssa29.

Conclusions

This study identified major chromosomal differences between European and North American Atlantic salmon. However, while gross structural differences were significant, the order of genetic markers at the fine-resolution scale was remarkably conserved. This is a good indication that information from the International Cooperation to Sequence the Atlantic salmon Genome, which is sequencing a European Atlantic salmon, can be transferred to Atlantic salmon from North America.
Learning from failure - rationale and design for a study about discontinuation of randomized trials (DISCO study)
Authors: Kasenda Benjamin , von Elm Erik B , You John , Blümle Anette , Tomonaga Yuki , Saccilotto Ramon , Amstutz Alain , Bengough Theresa , Meerpohl Jörg , Stegert Mihaela , Tikkinen Kari A O , Neumann Ignacio , Carrasco-Labra Alonso , Faulhaber Markus , Mulla Sohail , Mertz Dominik , Akl Elie A , Bassler Dirk , Busse Jason W , Ferreira-González Ignacio , Lamontagne Francois , Nordmann Alain , Rosenthal Rachel , Schandelmaier Stefan , Sun Xin , Vandvik Per O , Johnston Bradley C , Walter Martin A , Burnand Bernard , Schwenkglenks Matthias , Bucher Heiner C , Guyatt Gordon H , Briel Matthias
Published: August 2012

Background

Randomized controlled trials (RCTs) may be discontinued because of apparent harm, benefit, or futility. Other RCTs are discontinued early because of insufficient recruitment. Trial discontinuation has ethical implications, because participants consent on the premise of contributing to new medical knowledge, Research Ethics Committees (RECs) spend considerable effort reviewing study protocols, and limited resources for conducting research are wasted. Currently, little is known regarding the frequency and characteristics of discontinued RCTs.

Methods/Design

Our aims are, first, to determine the prevalence of RCT discontinuation for specific reasons; second, to determine whether the risk of RCT discontinuation for specific reasons differs between investigator- and industry-initiated RCTs; third, to identify risk factors for RCT discontinuation due to insufficient recruitment; fourth, to determine at what stage RCTs are discontinued; and fifth, to examine the publication history of discontinued RCTs.

We are currently assembling a multicenter cohort of RCTs based on protocols approved between 2000 and 2002/3 by 6 RECs in Switzerland, Germany, and Canada. We are extracting data on RCT characteristics and planned recruitment for all included protocols. Completion and publication status is determined using information from correspondence between investigators and RECs, publications identified through literature searches, or by contacting the investigators. We will use multivariable regression models to identify risk factors for trial discontinuation due to insufficient recruitment. We aim to include over 1000 RCTs of which an anticipated 150 will have been discontinued due to insufficient recruitment.

Discussion

Our study will provide insights into the prevalence and characteristics of RCTs that were discontinued. Effective recruitment strategies and the anticipation of problems are key issues in the planning and evaluation of trials by investigators, Clinical Trial Units, RECs and funding agencies. Identification and modification of barriers to successful study completion at an early stage could help to reduce the risk of trial discontinuation, save limited resources, and enable RCTs to better meet their ethical requirements.
Study of the effect of antiviral therapy on homocysteinemia in hepatitis C virus- infected patients
Authors: Mustafa Mubin , Hussain Sofia , Qureshi Saleem , Malik Salman Akbar , Kazmi Ali Raza , Naeem Muhammad
Published: August 2012

Background

Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver disease (CLD). About 80% of those exposed to the virus develop a chronic infection. Hyperhomocysteinemia, which is an independent risk factor for atherosclerotic vascular disease and thromboembolism, may develop in HCV-infected patients although altered alanine amino transferase (ALT) enzyme levels are generally associated with damage to liver cells. The gold standard therapy for chronic hepatitis C patients is pegylated interferon combined with an anti-viral drug (ribavirin). The current study aimed to investigate the effect of antiviral therapy on plasma homocysteine (Hcy) levels in HCV patients in addition to other parameters.

Methods

532 HCV-infected patients and 70 healthy controls were recruited for the study. All patients were subjected to laboratory investigations including HCV-RNA levels, complete blood cell counts, serum levels of homocysteine, ALT, alkaline phosphatase (ALP), lipid profile and liver ultrasonographic examination. The outcome of treatment with pegylated interferon α plus ribavirin treatment and sustained virologic response (SVR) was determined 6–9 months post-therapy.

Results

Hyperhomocysteinemia was found in 91.35% of HCV-infected patients. The difference in plasma Hcy concentrations reached statistical significance between the patient and control groups. ALT, cholesterol and triglycerides (TGs) levels were found higher than normal in the patients group. After receiving a combined therapy for 24 weeks, 43.66% patients showed an SVR (responders); 30.98% patients were non-responders while 25.35% patients initially responded to therapy but again retrieved positive status of HCV infection six months post-therapy (relapse-cirrhotic patients). The mean levels of plasma Hcy, ALT and ALP were significantly reduced in responders within 10 weeks of therapy when compared with non-responders and relapse-cirrhotic patients.

Conclusion

Elevated homocysteine levels in serum due to HCV infection can be reduced to normal range with the standard interferon α plus ribavirin treatment. This study highlights the significance of the measurement of serum homocysteine levels in the diagnosis and monitoring of HCV infection treatment in addition to other laboratory parameters.
Influence of HTLV-1 on the clinical, microbiologic and immunologic presentation of tuberculosis
Authors: Bastos Maria de Lourdes , Santos Silvane B , Souza Anselmo , Finkmoore Brooke , Bispo Ohana , Barreto Tasso , Cardoso Ingrid , Bispo Iana , Bastos Flávia , Pereira Daniele , Riley Lee , Carvalho Edgar M
Published: August 2012

Background

HTLV-1 is associated with increased susceptibility to Mycobacterium tuberculosis infection and severity of tuberculosis. Although previous studies have shown that HTLV-1 infected individuals have a low frequency of positive tuberculin skin test (TST) and decreasing in lymphoproliferative responses compared to HTLV-1 uninfected persons, these studies were not performed in individuals with history of tuberculosis or evidence of M. tuberculosis infection. Therefore the reasons why HTLV-1 infection increases susceptibility to infection and severity of tuberculosis are not understood.The aim of this study was to evaluate how HTLV-1 may influence the clinical, bacteriologic and immunologic presentation of tuberculosis.

Methods

The study prospectively enrolled and followed 13 new cases of tuberculosis associated with HTLV-1 (cases) and 25 patients with tuberculosis without HTLV-1 infection (controls). Clinical findings, bacterial load in the sputum, x-rays, immunological response and death were compared in the two groups.

Results

There were no differences in the demographic, clinical and TST response between the two study groups. IFN-γ and TNF-α production was higher in unstimulated cultures of mononuclear cells of case than in control patients (p < 0.01). While there was no difference in IFN-γ production in PPD stimulated cultures, TNF-α levels were lower in cases than in controls (p = 0.01). There was no difference in the bacterial load among the groups but sputum smear microscopy results became negative faster in cases than in controls. Death only occurred in two co-infected patients.

Conclusion

While the increased susceptibility for tuberculosis infection in HTLV-1 infected subjects may be related to impairment in TNF-α production, the severity of tuberculosis in co-infected patients may be due to the enhancement of the Th1 inflammatory response, rather than in their decreased ability to control bacterial growth.
Long-term effects of cranial irradiation and intrathecal chemotherapy in treatment of childhood leukemia: a MEG study of power spectrum and correlated cognitive dysfunction
Authors: Daams Marita , Schuitema Ilse , van Dijk Bob W , van Dulmen-den Broeder Eline , Veerman Anjo JP , van den Bos Cor , de Sonneville Leo MJ
Published: August 2012

Background

Prophylaxis to prevent relapses in the central nervous system after childhood acute lymphoblastic leukemia (ALL) used to consist of both intrathecal chemotherapy (CT) and cranial irradiation (CRT). CRT was mostly abolished in the eighties because of its neurotoxicity, and replaced with more intensive intrathecal CT. In this study, a group of survivors treated with CRT before 1983 and another group treated without CRT thereafter are investigated 20–25 years later, giving a much stronger perspective on long-term quality of life than previous studies. The outcomes will help to better understand these groups’ current needs and will aid in anticipating late effects of prophylactic CRT that is currently applied for other diseases. This study evaluates oscillatory neuronal activity in these long-term survivors. Power spectrum deviations are hypothesized to correlate with cognitive dysfunction.

Methods

Resting state eyes-closed magnetoencephalography (MEG) recordings were obtained from 14 ALL survivors treated with CT + CRT, 18 treated with CT alone and 35 controls. Relative spectral power was calculated in the δ, θ, α1, α2, β and γ frequency bands. The Amsterdam Neuropsychological Tasks (ANT) program was used to assess cognition in the executive functions domain. MEG data and ANT scores were correlated.

Results

In the CT + CRT group, relative θ power was slightly increased (p = 0.069) and α2 power was significantly decreased (p = 0.006). The CT + CRT group performed worse on various cognitive tests. A deficiency in visuomotor accuracy, especially of the right hand, could be clearly associated with the deviating regional θ and α2 powers (0.471 < r < 0.697). A significant association between decreased regional α2 power and less attentional fluctuations was found for CT + CRT patients as well as controls (0.078 < r < 0.666). Patients treated with CT alone displayed a power spectrum similar to controls, except for a significantly increased level of left frontal α2 power (p = 0.030).

Conclusions

The tendency towards global slowing of brain oscillatory activity, together with the fact that dementia has been reported as a late effect of CRT and the neuropsychological deficiencies currently present, suggest that the irradiated brain might be aging faster and could be at risk for early‐onset dementia. The CT group showed no signs of early aging.
High incidence of microsatellite instability and loss of heterozygosity in three loci in breast cancer patients receiving chemotherapy: a prospective study
Authors: Kamat Nasir , Khidhir Mohammed A , Jaloudi Mohammed , Hussain Sabir , Alashari Mouied M , Al Qawasmeh Khaled H , Rannug Ulf
Published: August 2012

Background

The aim of the study was to evaluate potential chemotherapy-induced microsatellite instability, loss of heterozygosity, loss of expression in mismatch repair proteins and associations with clinical findings in breast cancer patients, especially resistance to chemotherapy and/or development of other tumors in the four years following chemotherapy treatment.

Methods

A comprehensive study of chemotherapy-related effects with a follow-up period of 48 months post treatment was conducted. A total of 369 peripheral blood samples were collected from 123 de novo breast cancer patients. Microsatellite instability and loss of heterozygosity in five commonly used marker loci (including Tp53-Alu of the tumor suppressor gene TP53) were analyzed in blood samples. Sampling was conducted on three occasions; 4–5 weeks prior to the first chemotherapy session (pre-treatment), to serve as a baseline, followed by two consecutive draws at 12 weeks intervals from the first collection. Mismatch repair protein expression was evaluated in cancer tissues using immunohistochemistry for three mismatch-repair related proteins.

Results

A total of 70.7% of the patients showed microsatellite instability for at least one locus, including 18.6% marked as high-positive and 52.1% as low-positive; 35.8% showed loss of heterozygosity in addition to microsatellite instability, while 29.3% exhibited microsatellite stability. The following incidence rates for microsatellite instability and loss of heterozygosity were detected: 39.1% positive for Tp53-Alu, 31.1% for locus Mfd41, and 25.3% for locus Mfd28. A higher occurrence of loss of heterozygosity was noted with alleles 399 and 404 of Tp53-Alu. The mismatch repair protein expression analysis showed that the chemotherapy caused a loss of 29.3% in hMLH1 expression, and 18.7% and 25.2% loss in hMSH2 and P53 expression, respectively. A strong correlation between low or deficient hMSH2 protein expression and occurrence of mismatch repair/loss of heterozygosity events in Mfd41, Tp53-Alu, and Mfd28 was evident. A significant association between mismatch repair/loss of heterozygosity and incidence of secondary tumors was also established.

Conclusion

Our results suggest that microsatellite instability, loss of heterozygosity, and deficiency in mismatch repair may serve as early prognostic factors for potential chemotherapy-related side effects in breast cancer patients.
Does mentoring new peer reviewers improve review quality? A randomized trial
Authors: Houry Debra , Green Steven , Callaham Michael
Published: August 2012

Background

Prior efforts to train medical journal peer reviewers have not improved subsequent review quality, although such interventions were general and brief. We hypothesized that a manuscript-specific and more extended intervention pairing new reviewers with high-quality senior reviewers as mentors would improve subsequent review quality.

Methods

Over a four-year period we randomly assigned all new reviewers for Annals of Emergency Medicine to receive our standard written informational materials alone, or these materials plus a new mentoring intervention. For this program we paired new reviewers with a high-quality senior reviewer for each of their first three manuscript reviews, and asked mentees to discuss their review with their mentor by email or phone. We then compared the quality of subsequent reviews between the control and intervention groups, using linear mixed effects models of the slopes of review quality scores over time.

Results

We studied 490 manuscript reviews, with similar baseline characteristics between the 24 mentees who completed the trial and the 22 control reviewers. Mean quality scores for the first 3 reviews on our 1 to 5 point scale were similar between control and mentee groups (3.4 versus 3.5), as were slopes of change of review scores (-0.229 versus -0.549) and all other secondary measures of reviewer performance.

Conclusions

A structured training intervention of pairing newly recruited medical journal peer reviewers with senior reviewer mentors did not improve the quality of their subsequent reviews.
Burden of out-of-pocket expenditure for road traffic injuries in urban India
Authors: Kumar G Anil , Dilip T Ramachandran , Dandona Lalit , Dandona Rakhi
Published: August 2012

Background

Road traffic injuries (RTI) are an increasing public health problem in India where out-of-pocket (OOP) expenditures on health are among the highest in the world. We estimated the OOP expenses for RTI in a large city in India.

Methods

Information on medical and non-medical expenditure was documented for RTI cases of all ages that reported alive or dead to the emergency departments of two public hospitals and a large private hospital in Hyderabad. Differential risk of catastrophic OOP total expenditure (COPE-T) and medical expenditure (COPE-M), and distress financing was assessed for 723 RTI cases that arrived alive at the study hospitals with multiple logistic regression. Catastrophic expenditure was defined as expenditure > 25% of the RTI patient’s annual household income. Variation in intensity of COPE-M in RTI was assessed using multiple classification analysis (MCA).

Results

The median OOP medical and non-medical expenditure was USD 169 and USD 163, respectively. The prevalence of COPE-M and COPE-T was 21.9% (95% CI 18.8-24.9) and 46% (95% CI 42–49.3), respectively. Only 22% had access to medical insurance. Being admitted to a private hospital (OR 5.2, 95% CI 2.7–9.9) and not having access to insurance (OR 3.8, 95% CI 1.9–7.6) were significantly associated with risk of having COPE – M. Similar results were seen for COPE - T. MCA analysis showed that the burden of OOP medical expenditure was mainly associated with in-patient days in hospital (Eta =0.191). Prevalence of distress financing was 69% (95% CI 65.5-72.3) with it being significantly higher for those reporting to the public hospitals (OR 2.8, 95% CI 1.7-4.6), those belonging to the lowest per capita annual household income quartile (OR 7.0, 95% CI 3.7-13.3), and for those without insurance access (OR 3.4, 95% CI 2.0-5.7).

Conclusions

This paper has outlined the high burden of out-of-pocket medical and total expenditure associated with RTI in India. These data reinforce the need for implementing more effective financial protection mechanisms in India against the high out-of-pocket expenditure incurred on RTI.
Artemisinin resistance containment project in Thailand. II: responses to mefloquine-artesunate combination therapy among falciparum malaria patients in provinces bordering Cambodia
Authors: Satimai Wichai , Sudathip Prayuth , Vijaykadga Saowanit , Khamsiriwatchara Amnat , Sawang Surasak , Potithavoranan Thanapon , Sangvichean Aumnuyphan , Delacollette Charles , Singhasivanon Pratap , Kaewkungwal Jaranit , Lawpoolsri Saranath
Published: August 2012

Background

The area along the Thai-Cambodian border is considered an epicenter of anti-malarial drug resistance. Recently, parasite resistance to artemisinin-based therapies has been reported in the area. The artemisinin resistance containment project was initiated in November 2008, with the aim to limit resistant parasites and eliminate malaria in this region. This study describes the response to artemisinin-based therapy among falciparum malaria patients in the area, using data from the malaria surveillance programmed under the containment project.

Methods

The study was conducted in seven provinces of Thailand along the Thai-Cambodian border. Data of Plasmodium falciparum-positive patients during January 2009 to December 2011 were obtained from the electronic malaria information system (eMIS) Web-based reporting system. All P. falciparum cases were followed for 42 days, as the routine case follow-up protocol. The demographic characteristics of the patients were described. Statistical analysis was performed to determine the cure rate of the current standard anti-malarial drug regimen--mefloquine-artesunate combination therapy (MAS). The proportion of patients who remained parasite-positive at each follow-up day was calculated. In addition, factors related to the delayed parasite clearance on day-3 post-treatment, were explored.

Results

A total of 1,709 P. falciparum-positive cases were reported during the study period. Almost 70% of falciparum cases received MAS therapy (n = 1,174). The majority of cases were males, aged between 31 and 50 years. The overall MAS cure rate was >90% over the three-year period. Almost all patients were able to clear the parasite within 7 to 14 days post-treatment. Approximately 14% of patients undergoing MAS remained parasite-positive on day-3. Delayed parasite clearance was not significantly associated with patient gender, age, or citizenship. However, delayed parasite clearance varied across the study area.

Conclusion

Anti-malarial drug-resistant parasites should be closely monitored in the area along the Thai-Cambodian border. Although the MAS cure rate in this study area was above 90%, an increasing trend of treatment failure has been reported in neighboring parts. Effective malaria surveillance is an important component to monitor drug-resistance in the malaria containment project.
Prognosis of breast cancer is associated with one-carbon metabolism related nutrients among Korean women
Authors: Lee Yunhee , Lee Sang-Ah , Choi Ji-Yeob , Song Minkyo , Sung Hyuna , Jeon Sujee , Park Sue K , Yoo Keun-Young , Noh Dong-Young , Ahn Sei-Hyun , Kang Daehee
Published: August 2012

Background

The 5-year survival rate for breast cancer among Korean women has increased steadily; however, breast cancer remains the leading cause of cancer mortality among women. One-carbon metabolism, which requires an adequate supply of methyl group donors and B vitamins, may affect the prognosis of breast cancer. This aim of this study was to investigate the associations of dietary intake of vitamin B2, vitamin B6 and folate before diagnosis on the prognosis of breast cancer.

Methods

We assessed the dietary intake using a food frequency questionnaire with 980 women who were newly diagnosed and histopathologically confirmed to have primary breast cancer from hospitals in Korea, and 141 disease progression events occurred. Cox’s proportional hazard regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) adjusting for age, education, recruitment sites, TNM stage, hormone status, nuclear grade and total calorie.

Results

There was no significant association between any one-carbon metabolism related nutrients (vitamin B2, B6 and folate) and the progression of breast cancer overall. However, one-carbon metabolism related nutrients were associated with disease progression in breast cancer patients stratified by subtypes. In ER + and/or PR + breast cancers, no association was observed; however, in ER–/PR– breast cancers, a high intake of vitamin B2 and folate statistically elevated the HR of breast cancer progression (HR = 2.28; 95% CI, 1.20-4.35, HR = 1.84; 95% CI, 1.02-3.32, respectively) compared to a low intake. This positive association between the ER/PR status and progression of the disease was profound when the nutrient intakes were categorized in a combined score (Pinteraction = 0.018). In ER–/PR– breast cancers, high combined scores were associated with a significantly poor DFS compared to those belonging to the low score group (HR = 3.84; 95% CI, 1.70-8.71).

Conclusions

In conclusion, our results suggest that one-carbon related nutrients have a role in the prognosis of breast cancer depending on the ER/PR status.
Internalization of paramagnetic phosphatidylserine-containing liposomes by macrophages
Authors: Geelen Tessa , Yeo Sin Yuin , Paulis Leonie EM , Starmans Lucas WE , Nicolay Klaas , Strijkers Gustav J
Published: August 2012

Background

Inflammation plays an important role in many pathologies, including cardiovascular diseases, neurological conditions and oncology, and is considered an important predictor for disease progression and outcome.In vivoimaging of inflammatory cells will improve diagnosis and provide a read-out for therapy efficacy. Paramagnetic phosphatidylserine (PS)-containing liposomes were developed for magnetic resonance imaging (MRI) and confocal microscopy imaging of macrophages. These nanoparticles also provide a platform to combine imaging with targeted drug delivery.

Results

Incorporation of PS into liposomes did not affect liposomal size and morphology up to 12 mol% of PS. Liposomes containing 6 mol% of PS showed the highest uptake by murine macrophages, while only minor uptake was observed in endothelial cells. Uptake of liposomes containing 6 mol% of PS was dependent on the presence of Ca2+and Mg2+. Furthermore, these 6 mol% PS-containing liposomes were mainly internalized into macrophages, whereas liposomes without PS only bound to the macrophage cell membrane.

Conclusions

Paramagnetic liposomes containing 6 mol% of PS for MR imaging of macrophages have been developed.In vitrothese liposomes showed specific internalization by macrophages. Therefore, these liposomes might be suitable forin vivovisualization of macrophage content and for (visualization of) targeted drug delivery to inflammatory cells.
Clinical characteristics that distinguish eosinophilic organ infiltration from metastatic nodule development in cancer patients with eosinophilia
Authors: Lee Taehoon , Lee Yoon Su , Yoon Sun Young , Kim Su-Jeong , Bae Yun-Jeong , Kwon Hyouk-Soo , Cho You Sook , Moon Hee-Bom , Kim Tae-Bum
Published: August 2012

Background

When new space-occupying lesions are observed together with peripheral blood eosinophilia in patients diagnosed with cancer, the possibility of eosinophilic organ involvement should be differentiated from metastasis of primary cancer, since a misdiagnosis could lead to unnecessary chemotherapy. The aim of this study is to identify the clinical characteristics of eosinophilic organ involvement that distinguish it from distant metastasis in patients with primary cancer.

Methods

The medical records of 43 cancer patients who developed hepatic or pulmonary nodules with peripheral blood eosinophilia between January 2005 and February 2010 in the Asan Medical Center (Seoul) were reviewed. Eosinophilic infiltration and distant metastasis were identified on the basis of pathological findings and radiological features. Fisher’s exact test, χ
2 test or Mann-Whitney test were used for statistical analysis.

Results

In total, 33 patients (76%) were diagnosed with eosinophilic infiltration, 5 (12%) with cancer metastasis and 5 (12%) had undetermined diagnoses. Compared to the patients with metastases, the patients with eosinophilic infiltration were significantly more likely to have serology indicating a parasitic infection, a history of eating raw food, high serum levels of total IgE, normal liver function, normal C-reactive protein levels, a normal erythrocyte sedimentation rate, and fewer and smaller nodules. The most common underlying malignancy in the eosinophilic organ infiltration group was stomach cancer. Physicians tended to neglect the eosinophilia in patients with a history of cancer.

Conclusions

Several clinical characteristics of eosinophilic organ infiltration distinguish it from cancer metastasis. Physicians should make greater efforts to determine the causes of organ involvement with peripheral blood eosinophilia, especially in cancer patients.