bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Comparability and Availability of Private Health Expenditure Data in Health Accounts in the Asia-Pacific Region: A Case of India
Authors: Rout Sarit Kumar
Published: August 2012

National Health Accounts is a well-designed and accepted tool used globally to track the flow of funds in the health sector. It systematically analyzes the sources of funds, their use by different providers and delivery of services in the health sector. Providing a framework to collect and analyze health spending and its use, this tool provides inputs in designing policy, monitoring and evaluation of various programmes. Producing national health accounts on a regular basis in India is fraught with many challenges and lack of accurate data for some components of private sector health expenditure is a major constraint. Accounting for more than 75 per cent of health expenditure by the private sector, this requires systematic sources of data for production of regular health accounts. As on date, estimation of expenditure by local bodies, firms, and NGOs is based upon some independent surveys. The last two health accounts provided some estimates based upon this. For strengthening the health accounts there should be appropriate mechanisms in place for production of private sector data on a regular basis. This article provides a systematic analysis of sources, estimation process and constraints in estimation of private sector health expenditure in India.
Optimal time-delayed boundary control of beams using wavelets
Authors: Kucuk Ismail , Sadek Ibrahim
Published: August 2012

Time delays exist in active control systems. Although a time delay in most cases is small, it results in the actuator applying energy to the control system with a time delay. This might cause instability of the dynamic systems and degrade the performance of the control systems. The objective of the present work is to propose a feasible methodology that can achieve good control performance for a dynamic beam structure system by time-delayed boundary torque actuators. The control problem is to determine optimal time-delayed boundary control by minimizing a given performance criterion. The performance criterion is specified as a weighted quadratic functional of the dynamic responses of the beam which is to be minimized at a specified terminal time using continuous time-delayed torque actuators. The modal expansion approach is used to convert the optimal control problem of a distributed parameter system into the optimal control problem of a linear lumped parameter system (LPS). A direct state-control parameterization approach is proposed where wavelets are employed to solve time-delayed LPS. The operational matrices of integration and delay are utilized to reduce the solution of linear time-varying delayed systems to the solution of algebraic equations. A numerical simulation is presented to illustrate the efficiency of the proposed control algorithm.
Drawing Lines in the Journalistic Sand
Authors: Berkowitz Dan , Gutsche Robert E.
Published: August 2012

In mid-December 2010, The Daily Show host Jon Stewart asked Congress to address the health care needs of 9/11 rescue workers—which it did. Shortly after, the New York Times published an analysis piece comparing Stewart to the legendary broadcaster Edward R. Murrow. This article explores how collective memory of Murrow was used by both mainstream media and the blogosphere to negotiate membership boundaries of journalism itself, with analysis conducted through textual analysis of online mainstream news texts and blog postings.
Disaster News
Authors: Houston J. Brian , Pfefferbaum Betty , Rosenholtz Cathy Ellen
Published: August 2012

This research examines mass media depictions of major American natural disasters that occurred between 2000 and 2010. Results indicate that mass media cover natural disasters for shorter periods of time than they do other issues; that media coverage tends to focus on the current impact of disasters on humans, the built environment, and the natural environment; that disaster economics is an important topic; that disaster media coverage generally focuses on the state and region related to the event; and that disaster news is largely about what is happening now.
Disintegration of chemotherapy tablets for oral administration in patients with swallowing difficulties
Authors: Siden Rivka , Wolf Matthew
Published: August 2012

Purpose:

The administration of oral chemotherapeutic drugs can be problematic in patients with swallowing difficulties. Inability to swallow solid dosage forms can compromise compliance and may lead to poor clinical outcome. The current technique of tablet crushing to aid in administration is considered an unsafe practice. By developing a technique to disintegrate tablets in an oral syringe, the risk associated with tablet crushing can be avoided. The purpose of this study was to determine the feasibility of using disintegration in an oral syringe for the administration of oral chemotherapeutic tablets. Eight commonly used oral chemotherapeutic drugs were tested.

Methods:

Tablets were placed in an oral syringe and allowed to disintegrate in tap water. Various volumes and temperatures were tested to identify which combination allows for complete disintegration of the tablet in the shortest amount of time. The oral syringe disintegration method was considered feasible if disintegration occurred in £≤15 min and in ≤£20 mL of water and the dispersion passed through an oral syringe tip.

Results:

The following tablets were shown to disintegrate within 15 min and in <20 mL of water: busulfan, cyclophosphamide 50 mg, dasatinib, imatinib, methotrexate, and thioguanine. For these drugs, drug-specific information pamphlets can be prepared for patient or caregiver use. Mercaptopurine, cyclophosphamide 25 mg, and mitotane tablets did not pass the disintegration test.

Conclusion:

Disintegrating oral chemotherapeutic tablets in a syringe provides a closed system to administer hazardous drugs and allows for the safe administration of oral chemotherapeutic drugs in a tablet form to patients with swallowing difficulties.
Hyperammonaemia due to cobalamin malabsorption in a cat with exocrine pancreatic insufficiency
Authors: Watanabe Takayuki , Hoshi Katsuichiro , Zhang Chunhua , Ishida Yuzuru , Sakata Ikuo
Published: August 2012

A 10-year-old domestic shorthair cat showed anorexia, lethargy and ptyalism with hyperammonaemia. Portosystemic shunts were not identified by computed tomography angiography. Biopsy results revealed mild interstinal nephritis and no lesion in the liver. Analysis of urine revealed the presence of a high methylmalonic acid (MMA) concentration. Serum cobalamin (vitamin B12) and serum feline trypsin-like immunoreactivity levels were also markedly low. The cat was diagnosed as having exocrine pancreatic insufficiency (EPI). After 5 weeks of parenteral cobalamin supplementation, serum cobalamin concentration had increased and urinary MMA concentration had decreased. This case suggests that hyperammonaemia may be caused by accumulation of MMA due to cobalamin malabsorption secondary to feline EPI.
The effect of nanoclay reinforcement on the rolling contact fatigue behaviour of polyamide
Authors: Charles D Finney , Gnanamoorthy R , Parag R
Published: August 2012

Polymer nanocomposite has received great research interest in design of engineering components owing to its remarkable improvement in tribological characteristics. Rolling contact fatigue is a predominant failure mode of the many functional components like gears, bearings, cams, ball screw rods and rail wheels. Nanosize clay fillers were dispersed into the polymer using melt intercalation method to produce polymer nanocomposite material. Injection-molded disc-type specimens were made to run against each other on twin-disc test rig designed in-house. To understand the behaviour of the materials, rolling contact fatigue behaviour against different contact loads under constant speed were studied. Rolling contact fatigue testing of polymer nanocomposite has revealed significant difference from the pristine PA6 behaviour in failure modality and temperature rise. Addition of nanoclay to polymer although improved the modulus and strength of the nanocomposite, deteriorated the rolling contact behaviour. Rolling contact fatigue performance of PA6 was better than that of the clay-reinforced polymer nanocomposite under all tested conditions. Polymer nanocomposite materials have shown poor wear resistance as the specific wear rate was calculated to be higher for PNC materials under rolling contact fatigue conditions. Difference in surface temperature rise in PA6 and polymer nanocomposite has led to the different failure mechanism and reduction in rolling contact fatigue life of polymer nanocomposite materials.
Walking speed, rather than Expanded Disability Status Scale, relates to long-term patient-reported impact in progressive MS
Authors: Bosma LVAE , Kragt JJ , Polman CH , Uitdehaag BMJ
Published: August 2012

Objective:

To study the relationships between 1–2 year changes in well-known physician-rated measurements (Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT)) and the long-term (≥ 5 years) outcome in patient-reported outcome (PRO) measures (Multiple Sclerosis Impact Scale (MSIS-29), Multiple Sclerosis Walking Scale (MSWS-12)) that reflect the patient-perceived impact of disease, in progressive MS.

Methods:

We selected all progressive patients having at least two complete visits within 1-2 years, from a larger cohort of prospectively-followed MS patients. These were invited for another visit, at least 5 years later, consisting of another series of similar examinations, plus 2 PRO scales: the MSIS-29 and MSWS-12. We explored associations between early changes in physician-rated measurements and the long-term outcome as per the PRO measures.

Results:

In this study,134 patients fulfilled the selection criteria. We found that early change in T25FW was the only physician-rated change that was significantly related to long-term physical impact experienced by the patient, as was assessed by MSIS-29 (Kruskal-Wallis test: χ2=7.8, p=0.020). Early T25FW change, and to a lesser degree early 9HPT change, were significantly related to the reported long-term walking limitations, as assessed by MSWS-12 (Kruskal-Wallis test: χ2=13.8 and p=0.001 for T25FW, χ2=6.5 and p=0.038 for 9HPT). None of the early physician-rated changes were related to the long-term psychological impact experienced by the patient.

Conclusion:

Early changes on physician-rated scales do have long-term impact in terms of potentially predictive value of outcomes for groups of patients in progressive MS, regarding walking limitations and more global physical impact. Surprisingly, early change in T25FW, rather than early change in EDSS, was significantly associated with longer-term patient-reported disease impact. Our study data support the value of using early physician-rated examinations in clinical trials in progressive MS.
MS risk genes are transcriptionally regulated in CSF leukocytes at relapse
Authors: Jernås Margareta , Malmeström Clas , Axelsson Markus , Olsson Caroline , Nookaew Intawat , Wadenvik Hans , Zetterberg Henrik , Blennow Kaj , Lycke Jan , Rudemo Mats , Olsson Bob
Published: August 2012

Background:

Infiltrating T-helper cells, cytotoxic T-cells, B-cells and monocytes are thought to mediate the damage to myelin, oligodendrocytes and axons in multiple sclerosis (MS), which results in progressive disability.

Objective:

The objective of this paper is to explore gene expression profiles of leukocytes in the cerebrospinal fluid (CSF) compartment of MS patients during relapse.

Methods:

Global gene expression was analyzed by DNA microarray analysis of cells in CSF from MS patients and controls, and verifications were performed with real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA).

Results:

Fifty percent of the recently described risk genes for MS and 28% of non-risk genes were differently expressed in MS patients compared to controls (χ2-test, p=7.7 × 10−5). Genes involved in T- and NK-cell processes were up-regulated, and genes involved in processes targeting innate immunity or B-cells were down-regulated in MS. Increased expression of EDN1 and CXCL11 and decreased expression of HMOX1 was verified with real-time PCR and increased expression of CXCL13 was verified with ELISA in CSF.

Conclusion:

DNA microarray analysis is useful in identifying differently expressed genes in CSF leukocytes, which may be important in MS in vivo. Our findings suggest that many of the risk genes for MS are differently expressed in the disease-mediating leukocytes that penetrate the blood-brain barrier.
Microstructural magnetic resonance imaging of cortical lesions in multiple sclerosis
Authors: Filippi M , Preziosa P , Pagani E , Copetti M , Mesaros S , Colombo B , Horsfield MA , Falini A , Comi G , Lassmann H , Rocca MA
Published: August 2012

Background:

Pathologic and magnetic resonance imaging (MRI) studies have shown that cortical lesions (CLs) are a frequent finding in multiple sclerosis (MS).

Objective:

To quantify microstructural damage in CLs and normal appearing (NA) cortex in relapse-onset MS patients at different stages of the disease.

Methods:

Brain double inversion recovery (DIR), diffusion tensor (DT) MRI and 3D T1-weighted scans were acquired from 35 relapsing–remitting (RR) patients, 23 secondary progressive (SP) patients, 12 benign (B) MS patients and 41 healthy controls (HC). Diffusivity values in CLs, cortex, white matter (WM) lesions and normal-appearing white matter (NAWM) were assessed.

Results:

Compared to HC, MS patients had a significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) in the cortex and NAWM. CLs had higher FA vs HC cortex and vs patients’ cortex. Compared to RRMS patients, SPMS patients had higher WM lesion volume, higher MD in the cortex, and more severe damage to the NAWM and WM lesions. Compared to SPMS patients, BMS patients had lower MD and FA of CLs. Damage in other compartments was similar between SPMS and BMS patients. Damage in CLs had a high power to discriminate BMS from SPMS (area under the curve: 79–91%), with high specificity (85%), sensitivity (100%) and accuracy (90%).

Conclusions:

Microstructural imaging features of CLs differ from those of WM lesions and are likely to reflect neuronal damage and microglial activation. The nature and extent of CL damage can be used to help distinguish the different MS clinical phenotypes.
Retinol levels are associated with magnetic resonance imaging outcomes in multiple sclerosis
Authors: Løken-Amsrud Kristin I , Myhr Kjell-Morten , Bakke Søren J , Beiske Antonie G , Bjerve Kristian S , Bjørnarå Bård T , Hovdal Harald , Lilleås Finn , Midgard Rune , Pedersen Tom , Benth Jūratė Šaltytė , Torkildsen Øivind , Wergeland Stig , Holmøy Trygve
Published: August 2012

Background:

Vitamin A has immunomodulatory properties and may regulate the transcription of genes involved in remyelination.

Objective:

To investigate the association between retinol and disease activity in multiple sclerosis (MS).

Methods:

Cohort study of 88 relapsing–remitting MS patients, originally included in a randomised placebo-controlled trial of omega-3 fatty acids in MS (the OFAMS study), followed prospectively for 24 months with repeated assessments of serum-retinol and magnetic resonance imaging (MRI). All patients were initiated on interferon β-1a after month 6.

Results:

Each 1 µmol/L increase in serum-retinol reduced the odds (95% confidence interval) for new T1 gadolinium enhanced (Gd+) lesions by 49 (8–70)%, new T2 lesions by 42 (2–66)%, and combined unique activity (CUA) by 46 (3–68)% in simultaneous MRI scans, and 63 (25–82)% for new T1Gd+ lesions, 49 (3–73)% for new T2 lesions and 43 (12–71)% for CUA the subsequent month. Serum-retinol also predicted new T1Gd+ and T2 lesions six months ahead. The associations were not affected by HLA-DRB1*15, or serum levels of 25-hydroxyvitamin D, eicosapentaenoic acid or docosahexaenoic acid.

Conclusion:

Serum retinol is inversely associated with simultaneous and subsequent MRI outcomes in RRMS.
Severe multiple sclerosis reactivation under fingolimod 3 months after natalizumab withdrawal
Authors: Daelman L , Maitrot A , Maarouf A , Chaunu MP , Papeix C , Tourbah A
Published: August 2012

We report the case of a woman with multiple sclerosis who developed a severe neurological condition following natalizumab (NZB) withdrawal and soon after fingolimod (FTY) initiation. FTY was started 3.5 months after a two-year NZB treatment. Fifteen days later, she suffered partial repetitive seizures followed by a tonicoclonic seizure. This was associated with attention difficulties and an increased asthenia. Brain MRI follow-up disclosed large demyelinating active lesions in favour of disease reactivation. This case suggests that FTY introduction may occur less than three months after NZB withdrawal.
The French Take Hollywood
Authors: Barthel-Bouchier Diane
Published: August 2012

While the United States dominates the global film market, strategies are available to non-U.S. filmmakers seeking to make their mark. Sociologist Diane Barthel-Bouchier discusses how the Oscar-winning French film, The Artist, used the strategies of solving the language problem, meeting cultural expectations, building connections with Hollywood insiders, and mounting a media charm offensive to win the 2012 Best Picture Oscar award.
Killadelphia
Authors: Dickinson James
Published: August 2012

Violent death is so commonplace in Philadelphia that it infuses the visual culture of the city with haunting imagery. Sociologist James Dickinson shows how memorial portraits, roadside shrines, sidewalk plaques, murals, billboards, and graffiti variously recall, memorialize, criticize, or comment on the epidemic of lethal violence in the City of Brotherly Love.
Park(ing) Day
Authors: Coombs Gretchen
Published: August 2012

Park(ing) Day has become an international phenomenom since its inception in 2005. Gretchen Coombs explains how this urban intervention questions the use of public space and reimagines how urban public spaces can be repurposed to benefit local communities.
The Rich and the Rest
Authors: Linneman Thomas J.
Published: August 2012

Using data from the General Social Survey, sociologist Thomas J. Linneman shows that conservatives and liberals increasingly differ regarding government action to reduce income inequality. Rich liberals support government action nearly as much as poor liberals, while among rich conservatives there is very little support for government action.
Public attitudes toward media control and incitement of conflicts in Eastern Africa
Authors: Kalyango Yusuf , Vultee Fred
Published: August 2012

Public opinion research in two post-conflict African countries, Ethiopia and Rwanda, offers new insights into how audiences view the trustworthiness and performance of different media and different ownership sectors. This survey examines how citizens of Rwanda and Ethiopia describe the role of mass media in covering conflicts and in stoking the attitudes that can lead to or worsen conflicts. State-owned media are widely used as a source of news, yet are also widely distrusted, particularly when covering conflicts. They are also seen as less reliable than the privately-owned media. Still, different levels of use and confidence in state media suggest that top-down reconciliation efforts can have measurable results. Media can play a role in damping the flames of ethnic conflict, much as they can play a role in fanning those flames.
Experience with the combination of dutasteride and tamsulosin in the long-term management of benign prostatic hyperplasia
Authors: Chughtai Bilal , Elterman Dean S. , Lee Richard , Te Alexis E. , Kaplan Steven A.
Published: August 2012

Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) commonly affect older men. These bothersome symptoms can lead to a decreased quality of life. Currently, two classes of drugs – α-adrenergic blockers and 5α-reductase inhibitors – are prescribed to treat LUTS secondary to BPH. Due to their different mechanisms of action, these medications work in a synergistic manner. Trials of combination therapy have been conducted to assess its effect compared with monotherapy. Current data support combination therapy in men with moderately enlarged prostates and moderate to severe symptoms.
Effect of Y2O3 particles on mechanical properties of gas metal arc weldments in low carbon steel
Authors: Sun L , Wang X B , Wang X , Liu C X
Published: August 2012

In this study, the influence of Y2O3 particles on the weld properties of low carbon steel was investigated by metallographic and mechanical tests. It was found that the microstructure of the fuse zone in the weld beam undergoes a significant change after adding Y2O3 particles. The amount of allotriomorphic ferrite increases, while that of the acicular ferrite decreases. Moreover, the size of the allotriomorphic ferrite decreases with the adding of the Y2O3 particles. On the other hand, the absorbed energy in the Charpy impact test increases, whereas the tensile strength almost keeps unchanged with adding of the Y2O3 particles. Furthermore, the hardness of the weld metal is nearly lowered to the level of that of the base metal due to the adding of the Y2O3 particles.
Measurement of arc pressure and shield gas pressure effect on surface of molten pool in TIG welding
Authors: Ham H-S , Oh D-S , Cho S-M
Published: August 2012

Tungsten inert gas (TIG) welding is most frequently used for arc study because it is clean and easy to control welding factor. Many researchers have been focused on the plasma stream to find out the relationship between vertex angle and penetration of the tungsten electrode in TIG welding. Moreover, researchers studied the characteristics of vertex angle and arc pressure and heat flux distribution of the tungsten electrode. In addition, they have carried out factors that have influence on the behaviour of the molten pool. Previous studies assumed that arc pressure was dominant for the force that physically works on the surface of the molten pool, neglecting the shield gas pressure. In addition, they have been focused on the protection of molten weld pool from exposure to the atmosphere. The object of this study is to investigate the effect of shield gas pressure on the surface of the molten pool by measuring the distribution of arc pressure and shield gas pressure compared with arc physical results of previous researches. In this study, we measured the distribution of arc pressure and shield gas pressure on the water cooled copper plate by changing the setting shield gas pressure and shield gas cup inside diameter. As the setting shield gas pressure increased and the shield gas cup diameter decreased, the arc radius got narrower due to the thermal pinch effect. Maximum arc pressure was slightly affected by setting the shield gas pressure and shield gas cup diameter. However, the shield gas pressure on arc surroundings was raised with the increasing setting shield gas pressure and the decreasing gas cup inside diameter. Orbital welding with convex back bead was successfully performed through molten pool control by shield gas pressure adjustment.
Influence of tool thread on mechanical properties of dissimilar Al alloy friction stir spot welds
Authors: Ikuta A , Yin Y H , North T H
Published: August 2012

The influence of threaded and wear simulated (half thread) tools on the mechanical properties of dissimilar Al alloy friction stir spot welds is investigated. With lower tool rotational speed settings, the failure loads of Al 5754/Al 6111 lap joints made using a threaded tool were clearly higher than that of a half thread tool. However, the failure load of the joints made using a half thread tool increased when the tool rotational speed increased, and finally, as the rotational speed was further increased, the failure load became almost the same as the failure load of joints made using a threaded tool. In Al 5052/Al 6061 butt joints made using the threaded and half thread tools, the area of the stir zone on the bonded cross-section corresponded with the actual bonded region on the fracture surface. Therefore, the thread on the rotating pin has limited influence on the mechanical properties of the friction stir spot lap joints.
Weld zone characteristic and mechanical performance of in situ titanium matrix composites using gas tungsten arc welding (GTAW)
Authors: Mao J W , Wang M M , Wang L Q , Xue X B , Lu W J , Zhang D , Qin J N , Sun X J , Zhu X X
Published: August 2012

In situ TiBw and La2O3 reinforced titanium matrix composites were successfully fusion welded by the gas tungsten arc welding (GTAW) process and the weldability and feasibility for composites were studied, and uniform and defect free welds were produced with sound welding parameters. Microstructural observations showed that the joint has a distinctly identified weld zone characteristic. In addition, the distribution and size of TiBw in the weld became much more homogeneous and smaller. Moreover, the welded joints exhibited good mechanical properties at ambient temperature and the strength equal to the base metal at elevated temperature. The fracture mechanism of TiBw in the weld also was investigated.
Historic Aerial Photographic Archives for European Archaeology
Authors: Cowley David C. , Stichelbaut Birger B.
Published: August 2012

This article reviews the potential of archives of historic aerial photographs for European archaeology. Their roles in primary site discovery, in monitoring condition and material change, and in understanding landscape development with particular reference to the implementation of the European Landscape Convention are discussed. The major sources are briefly described and their characteristics outlined. The impacts that differing national and regional research traditions and heritage policy have on the use of these archival collections is discussed in the framework of issues of variable accessibility and approaches to ensuring appropriate uses, including identifying limitations.
Underwater Cultural Heritage and Maritime Archaeology in Croatia: An Overview
Authors: Rossi Irena Radić
Published: August 2012

Archaeological sites in Croatia's shallow waters are mentioned in written sources from the sixteenth century, and since the eighteenth century they have been used as evidence for the sinking of the Eastern Adriatic coast. It was at the end of the same century that the first Roman shipwreck in Croatian waters was reported. Sponge divers and coral hunters raised archaeological finds from the seabed off the Croatian coast, thus contributing to the creation of many private and monastic collections. Isolated campaigns aimed at protecting underwater cultural heritage began in the 1950s, and by 1970 these efforts became part of a well-organized system. Although the lack of systematic research remains notable, a number of surveys and rescue excavations have enriched our knowledge of ancient seafaring along the Croatian coast and have contributed to the study of the maritime environment. Some well-preserved shipwrecks from classical antiquity and the modern era show excellent potential for thein situprotection and presentation of Croatian underwater cultural heritage.
IgH partner breakpoint sequences provide evidence that AID initiates t(11;14) and t(8;14) chromosomal breaks in mantle cell and Burkitt lymphomas
Authors: Greisman Harvey A. , Lu Zhengfei , Tsai Albert G. , Greiner Timothy C. , Yi Hye Son , Lieber Michael R.
Published: August 2012

Previous studies have implicated activation-induced cytidine deaminase (AID) in B-cell translocations but have failed to identify any association between their chromosomal breakpoints and known AID target sequences. Analysis of 56 unclustered IgH-CCND1 translocations in mantle cell lymphoma across the ∼ 344-kb bcl-1 breakpoint locus demonstrates that half of the CCND1 breaks are near CpG dinucleotides. Most of these CpG breaks are at CGC motifs, and half of the remaining breaks are near WGCW, both known AID targets. These findings provide the strongest evidence to date that AID initiates chromosomal breaks in translocations that occur in human bone marrow B-cell progenitors. We also identify WGCW breaks at the MYC locus in Burkitt lymphoma translocations and murine IgH-MYC translocations, both of which arise in mature germinal center B cells. Finally, we propose a developmental model to explain the transition from CpG breaks in early human B-cell progenitors to WGCW breaks in later stage B cells.
A novel hierarchical prognostic model of AML solely based on molecular mutations
Authors: Grossmann Vera , Schnittger Susanne , Kohlmann Alexander , Eder Christiane , Roller Andreas , Dicker Frank , Schmid Christoph , Wendtner Clemens-Martin , Staib Peter , Serve Hubert , Kreuzer Karl-Anton , Kern Wolfgang , Haferlach Torsten , Haferlach Claudia
Published: August 2012

The karyotype is so far the most important prognostic parameter in acute myeloid leukemia (AML). Molecular mutations have been analyzed to subdivide AML with normal karyotype into prognostic subsets. The aim of this study was to develop a prognostic model for the entire AML cohort solely based on molecular markers. One thousand patients with cytogenetic data were investigated for the following molecular alterations: PML-RARA, RUNX1-RUNX1T1, CBFB-MYH11, FLT3-ITD, and MLL-PTD, as well as mutations in NPM1, CEPBA, RUNX1, ASXL1, and TP53. Clinical data were available in 841 patients. Based on Cox regression and Kaplan-Meier analyses, 5 distinct prognostic subgroups were identified: (1) very favorable: PML-RARA rearrangement (n = 29) or CEPBA double mutations (n = 42; overall survival [OS] at 3 years: 82.9%); (2) favorable: RUNX1-RUNX1T1 (n = 35), CBFB-MYH11 (n = 31), or NPM1 mutation without FLT3-ITD (n = 186; OS at 3 years: 62.6%); (3) intermediate: none of the mutations leading to assignment into groups 1, 2, 4, or 5 (n = 235; OS at 3 years: 44.2%); (4) unfavorable: MLL-PTD and/or RUNX1 mutation and/or ASXL1 mutation (n = 203; OS at 3 years: 21.9%); and (5) very unfavorable: TP53 mutation (n = 80; OS at 3 years: 0%; P < .001). This comprehensive molecular characterization provides a more powerful model for prognostication than cytogenetics.
Serum activity of DPPIV and its expression on lymphocytes in patients with melanoma and in people with vitiligo
Authors: Matić Ivana Z , Đorđić Marija , Grozdanić Nađa , Damjanović Ana , Kolundžija Branka , Erić-Nikolić Aleksandra , Džodić Radan , Šašić Miomir , Nikolić Srđan , Dobrosavljević Danijela , Rašković Sanvila , Andrejević Slađana , Gavrilović Dušica , Cordero Oscar J , Juranić Zorica D
Published: August 2012

Background

Dipeptidyl peptidase IV, a multifunctional serine protease, is implicated in regulation of malignant transformation, promotion and further progression of cancer, exerting tumor-suppressing or even completely opposite - tumor-promoting activities.

The aim of present research was to determine the serum DPPIV activity, as well as the percentages of CD26+ lymphocytes, CD26+ overall white blood cells and the mean fluorescence intensity of CD26 expression on lymphocytes in patients with melanoma, people with vitiligo and in healthy controls.

Methods

The activity of DPPIV in serum was determined by colorimetric test. Expression of DPPIV (as CD26) on immunocompetent peripheral white blood cells was done using flow cytometry analysis.

Results

Data from our study show for the first time statistically significant decrease: in the serum DPPIV activity, in the percentage of CD26+ overall white blood cells and in the percentage of lymphocytes in patients with melanoma in comparison to healthy control people. In addition, significantly lower serum DPPIV activity was found in the group of patients with melanoma in relation to people with vitiligo too.

Conclusion

This study indicates the need for exploring the cause and the importance of the disturbances in the serum DPPIV activity and in the CD26 expression on immunocompetent cells in complex molecular mechanisms underlying the development and progression of melanoma.
Effect of exercise on chemically-induced colitis in adiponectin deficient mice
Authors: Saxena Arpit , Fletcher Emma , Larsen Bianca , Baliga Manjeshwar Shrinath , Durstine J Larry , Fayad Raja
Published: August 2012

Background

Inflammatory bowel diseases are associated with increased adiponectin (APN) levels, which may exert pro-inflammatory effects in these individuals. Since habitual exercise may increase APN, the aim of this study was to determine how exercise training affects mice with acute colitis.

Methods

Male adiponectin knock out (APNKO) and wild type (WT) mice (C57BL/6) were randomly assigned to 4 different groups: 1) Sedentary (SED); 2) Exercise trained (ET); 3) Sedentary with dextran sodium sulfate (DSS) treatment (SED + DSS); and 4) Exercise trained with DSS (ET + DSS). Exercise-trained mice ran at 18 m/min for 60 min, 5d/wk for 4 weeks. Subsequently, the ET + DSS and the SED + DSS mice received 2% DSS in their drinking water for 5 days (d), followed by 5d of regular water.

Results

The clinical symptoms of acute colitis (diarrhea, stool haemoccult, and weight loss) were unaffected by exercise and there was no difference between the APNKO and WT mice (p > 0.05) except on day 39. However, the clinical symptoms of the DSS-treated APNKO mice were worse than WT mice treated with DSS and had increased susceptibility to intestinal inflammation due to increased local STAT3 activation, higher IL-6, TNF-α, IL-1β and IL-10 levels, and as a result had increased intestinal epithelial cell proliferation (p < 0.05). Exercise training significantly decreased pro-inflammatory cytokines including IL-6, TNF-α and IL-1β (p < 0.05) in the DSS + EX APNKO mice but had no effect on epithelial cell proliferation. Exercise was also found to significantly decrease the phosphorylation expression of STAT3 in both WT and APNKO mice in DSS + EX group when compared to DSS + SED.

Conclusions

Exercise training may contribute in alleviating the symptoms of acute colitis and APN deficiency may exacerbate the intestinal inflammation in DSS-induced colitis.
Platelet-dependent thrombography gives a distinct pattern of in vitro thrombin generation after surgery with cardio-pulmonary bypass: potential implications
Authors: Said Rose , Regnault Véronique , Hacquard Marie , Carteaux Jean-Pierre , Lecompte Thomas
Published: August 2012

Background

Bleeding remains a potentially lethal complication of cardio-pulmonary bypass (CPB) surgery. The purpose of this study was to obtain a better insight into in vitro thrombin generation in the context of CPB.

Methods

We used Calibrated Automated Thrombography to assess blood coagulation of 10 low-risk patients operated for valve replacement with CPB, under 2 experimental conditions, one implicating platelets as platelet dysfunction has been described to occur during CPB.

Results

Our main finding was that CPB-induced coagulopathy was differently appreciated depending on the presence or absence of platelets: the decrease in thrombin generation was much less pronounced in their presence (mean endogenous thrombin potential change values before and after CPB were -3.9% in the presence of platelets and -39.6% in their absence).

Conclusion

Our results show that experimental conditions have a profound effect in the study of in vitro thrombin generation in the context of CPB.
Involvement of Tyr1472 Phosphorylation of NMDA Receptor NR2B Subunit in Postherpetic Neuralgia in Model Mice
Authors: Unezaki Sawako , Sasaki Atsushi , Mabuchi Tamaki , Matsumura Shinji , Katano Tayo , Nakazawa Takanobu , Nishio Naoko , Andoh Tsugunobu , Yamamoto Tadashi , Nakatsuka Terumasa , Kuraishi Yasushi , Ito Seiji
Published: August 2012

Background:

Postherpetic neuralgia is spontaneous pain and allodynia that persist long after the disappearance of the cutaneous lesions caused by herpes zoster. Inoculation of mice with herpes simplex virus-1 causes herpes zoster-like skin lesions and herpetic and postherpetic pain. Although NMDA receptors have been suggested to be involved in postherpetic pain as in other types of neuropathic pain, the neural mechanism remains unclear. NMDA receptor NR2B subunit is the most tyrosine-phosphorylated protein in the brain, and Tyr1472 is the major phosphorylation site of this subunit.

Results:

To elucidate the role of Tyr1472 phosphorylation of the NR2B subunit in herpetic and postherpetic allodynia, we inoculated herpes simplex virus-1 into the unilateral hind paw of knock-in mice with a mutation of Tyr1472 of the NR2B subunit to Phe (Y1472F-KI). On day 7 post-inoculation, acute herpetic allodynia was observed in more than 80% of the inoculated wild-type and Y1472F-KI mice. Y1472F-KI mice showed significantly reduced intensity and incidence of postherpetic allodynia on days 45–50 post-inoculation as compared with wild-type mice. The innervation in the skin at the postherpetic neuralgia phase was retained to a greater extent in the Y1472F-KI mice. The level of activating transcription factor-3 mRNA, a marker of axonal damage, increased much less in the dorsal root ganglia (DRGs) of Y1472F-KI mice than in those of wild-type mice; and the level of nerve growth factor mRNA significantly increased in wild-type mice, but not at all in Y1472F-KI mice on day 7 post-inoculation. Production of nerve growth factor was at the basal level in the skin of both groups of mice on day 50 post-inoculation. Nerve growth factor and glial cell-derived neurotrophic factor stimulated neurite outgrowth of cultured DRG neurons from Y1472F-KI mice, similarly or less so as they did the outgrowth of those from wild-type mice. Wild-type DRG neurons were more susceptible to glutamate neurotoxicity than Y1472F-KI ones.

Conclusions:

Taken together, the present data suggest that phosphorylation of the NR2B subunit at its Tyr1472 is involved in the development of postherpetic allodynia due to nerve damage and that the nerve damage at the acute herpetic phase is correlated with the incidence of postherpetic pain.
Effect of metabotropic glutamate receptor 3 genotype on N-acetylaspartate levels and neurocognition in non-smoking, active alcoholics
Authors: Xia Yan , Ma Dongying , Hu Jian , Tang Chunling , Wu Zheng , Liu Lei , Xin Feng
Published: August 2012

Background

We studied the effects of single nucleotide polymorphisms (SNPs) in the metabotropic glutamate receptor 3 (GRM3) gene on brain N-acetylaspartate (NAA) concentrations and executive function (EF) skills in non-smoking, active alcoholics, and evaluated associations between these variables.

Methods

SNPs (rs6465084, rs1468412, and rs2299225) in GRM3 were genotyped in 49 male, non-smoking, alcohol-dependent patients and 45 healthy control subjects using ligase detection reactions. NAA/creatine (Cr) ratios in left prefrontal gray matter (GM) and white matter (WM), left parietal GM, left parietal WM, and cerebellar vermis regions were measured by Proton1 H Magnetic resonance spectroscopy (MRS). EF was measured by the Wisconsin Card Sorting Test (WCST).

Results

Compared to controls, alcoholics had lower NAA/Cr ratios in prefrontal GM and WM regions and performed more poorly on all EF tests (P < 0.001). Alcoholics with the A/A genotype for SNP rs6465084 had lower NAA/Cr ratios in prefrontal GM and WM regions and had poorer EF skills than alcoholics who were G-carriers for this SNP (P < 0.01). Non-alcoholics with the A/A genotype for rs6465084 also had lower NAA/Cr levels in prefrontal GM and made more random errors in the WCST than G-carriers (P < 0.01). The A/A genotype group for SNP rs6465084 was significantly different from the G carriers for the variables of NAA/Cr ratios and WCST scores in both alcoholics and controls (P < 0.05). Alcoholics who were T-carriers for rs1468412 had lower NAA/Cr ratios in prefrontal GM and showed poorer EF skills (P < 0.05). No effects of rs2299225 genotype on NAA/Cr or executive skills were observed. NAA/Cr in left prefrontal regions correlated with certain parameters of EF testing in both alcoholics and controls (P < 0.05), but the significance of this correlation among alcoholics disappeared after adjustment for the effects of genotype.

Conclusions

Our results provide evidence that glutamate system dysfunction may play a role in the prefrontal functional abnormalities seen in alcohol dependence. It is possible that certain GRM3 SNP genotypes (the A/A genotype of rs6465084 and the T allele of rs1468412) may further lower NAA/Cr levels and EF skills in addition to the effect of alcohol.
In-vitro comparison of LC-DCP- and LCP-constructs in the femur of newborn calves – a pilot study
Authors: Hoerdemann Mona , Gédet Philippe , Ferguson Steven J , Sauter-Louis Carola , Nuss Karl
Published: August 2012

Background

To compare the biomechanical in-vitro characteristics of limited-contact dynamic compression plate (LC-DCP) and locking compression plate (LCP) constructs in an osteotomy gap model of femoral fracture in neonatal calves. Pairs of intact femurs from 10 calves that had died for reasons unrelated to the study were tested. A 7-hole LC-DCP with six 4.5 mm cortical screws was used in one femur and a 7-hole LCP with four 5.0 mm locking and two 4.5 mm cortical screws was used in the corresponding femur. The constructs were tested to failure by cyclic compression at a speed of 2 mm/s within six increasing force levels.

Results

The bone-thread interface was stripped in 21 of 80 cortical screws (26.3%) before a pre-set insertion torque of 3 Nm was achieved. Only 3 corresponding intact pairs of constructs could be statistically compared for relative structural stiffness, actuator excursion and width of the osteotomy gap. Relative structural stiffness was significantly greater, actuator excursion and width of the osteotomy gap were significantly smaller in the LCP constructs. While failure occurred by loosening of the screws in the LC-DCP constructs, locking constructs failed by cutting large holes in the soft distal metaphyseal bone.

Conclusions

An insertion torque sufficient to provide adequate stability in femurs of newborn calves could not be achieved reliably with 4.5 mm cortical screws. Another limiting factor for both constructs was the weak cancellous bone of the distal fracture fragment. LCP constructs were significantly more resistant to compression than LC-DCP constructs.
Coordinated Eph-ephrin signaling guides migration and axon targeting in the avian auditory system
Authors: Allen-Sharpley Michelle R , Cramer Karina S
Published: August 2012

Background

In the avian sound localization circuit, nucleus magnocellularis (NM) projects bilaterally to nucleus laminaris (NL), with ipsilateral and contralateral NM axon branches directed to dorsal and ventral NL dendrites, respectively. We previously showed that the Eph receptor EphB2 is expressed in NL neuropil and NM axons during development. Here we tested whether EphB2 contributes to NM-NL circuit formation.

Results

We found that misexpression of EphB2 in embryonic NM precursors significantly increased the number of axon targeting errors from NM to contralateral NL in a cell-autonomous manner when forward signaling was impaired. We also tested the effects of inhibiting forward signaling of different Eph receptor subclasses by injecting soluble unclustered Fc-fusion proteins at stages when NM axons are approaching their NL target. Again we found an increase in axon targeting errors compared to controls when forward signaling was impaired, an effect that was significantly increased when both Eph receptor subclasses were inhibited together. In addition to axon targeting errors, we also observed morphological abnormalities of the auditory nuclei when EphB2 forward signaling was increased by E2 transfection, and when Eph-ephrin forward signaling was inhibited by E6-E8 injection of Eph receptor fusion proteins.

Conclusions

These data suggest that EphB signaling has distinct functions in axon guidance and morphogenesis. The results provide evidence that multiple Eph receptors work synergistically in the formation of precise auditory circuitry.
Regression of syndesmophyte after bone marrow transplantation for acute myeloid leukemia in a patient with ankylosing spondylitis: a case report
Authors: Yang Hae Kyung , Moon Su-Jin , Shin Jae Ho , Kwok Seung-Ki , Park Kyung Su , Park Sung-Hwan , Kim Ho-Youn , Ju Ji Hyeon
Published: August 2012

Introduction

Disease progression of ankylosing spondylitis has been considered irreversible. However, we report a case of spontaneous regression of syndesmophyte development following allogeneic peripheral blood stem cell transplantation in a patient with acute myeloid leukemia, who was also diagnosed as having ankylosing spondylitis. To the best of our knowledge, this is the first case report presenting the partial radiologic regression of syndesmophytes.

Case presentation

A 39-year-old man with active ankylosing spondylitis achieved clinical remission and partial radiological regression of cervical spine syndesmophytes following a peripheral blood stem cell transplantation for acute myeloid leukemia. Our patient received an allogeneic peripheral blood stem cell transplantation following a pre-transplantation conditioning regimen of total body irradiation and cyclophosphamide. The donor was a human leukocyte antigen-matched 29-year-old man. Our patient has remained asymptomatic and has received no medication for ankylosing spondylitis for nearly three years.

Conclusions

Several explanations are proposed for the regression of syndesmophytes and clinical improvement in active ankylosing spondylitis observed in our patient, including changes in bone remodeling and immune reconstitution following stem cell transplantation, the effect of immunosuppressive agents, or fluctuation in the natural course of ankylosing spondylitis although further studies are required. The regression of syndesmophytes in ankylosing spondylitis in this case raises the possibility that stem cell transplantation might contribute to the development of a novel therapeutic strategy for treatment of the disease.
Gastrointestinal and urinary tract pathogenic infections among HIV seropositive patients at the Komfo Anokye Teaching Hospital in Ghana
Authors: Boaitey Yaw Agyekum , Nkrumah Bernard , Idriss Ali , Tay Samuel Crowther Kofi
Published: August 2012

Background

Gastrointestinal and urinary tract pathogenic infections are aggravating the incidence and progression of the Human Immunodeficiency Virus (HIV) infection into Acquired Immune Deficiency Syndrome (AIDS) more especially in the developing countries. This study was conducted to assess the common gastrointestinal and urinary infections among HIV/AIDS patients at the Komfo Anokye Teaching Hospital (KATH) in Ghana between April and December 2008.

Findings

This work reports on gastrointestinal and urinary tract pathogenic infections among 500 HIV seropositive and 300 HIV seronegative patients. There was a 35% (175/500) prevalence of intestinal parasites among HIV seropositive patients compared to 4.3% (13/300) in HIV seronegative patients. Giardia lamblia and Cryptosporidium accounted for 19% (95/500) and 14% (70/500) respectively, while Schistosoma mansoni, Strongyloides stercoralis and hookworm together accounted for 2% (10/500) of intestinal parasitic infections among the HIV seropositive patients. There was no significant difference (p > 0.05) in urinary parasitic infection between HIV seropositive 1% (2/500) and seronegative patients 0.7% (2/300). Most, 60 (86%) out of 70, of the urinary tract infection among the HIV seropositive patients was due to bacteria with E. coli being the most predominant isolate, 28 (47%) out of 60. There was no significant difference in infections based on age and gender.

Conclusion

G. lamblia and Cryptosporidium were the most common gastrointestinal parasites detected while bacteria accounted for majority of the urinary tract infections among the HIV seropositive patients at the hospital.