bluuebunny/crossref_metadata_2025_split huggingface dataset:
An assessment of Makerere University College of Health Sciences: optimizing health research capacity to meet Uganda’s priorities
Authors: Nankinga Ziadah , Kutyabami Paul , Kibuule Dan , Kalyango Joan , Groves Sara , Bollinger Robert C , Obua Celestino 
Published: March 2011

Abstract

Background
Health research is critical to the institutional mission of the Makerere College of Health Sciences (MakCHS). Optimizing the alignment of health research capacity at MakCHS with the health needs and priorities of Uganda, as outlined in the country’s Health Sector Strategic Plan (HSSP), is a deliberate priority, a responsibility, and a significant opportunity for research. To guide this strategic direction, an assessment of MakCHS’s research grants and publication portfolio was conducted.

Methods
A survey of all new and ongoing grants, as well as all publications, between January 2005 and December 2009 was conducted. Research, training, and education grants awarded to MakCHS’ constituent faculties and departments, were looked for through financial records at the college or by contact with funding organizations. Published manuscripts registered with PubMed, that included MakCHS faculty authors, were also analyzed.

Results
A total of 58 active grants were identified, of which 18 had been initiated prior to 2005 and there were an average of about eight new grants per year. Most grants funded basic and applied research, with major focus areas being HIV/AIDS (44%), malaria (19%), maternal and child health (14%), tuberculosis (11%), mental health (3%), and others (8%). MakCHS faculty were identified as Principal Investigators (PIs) in only 22 (38%) active grants. Grant funding details were only available for one third of the active grants at MakCHS. A total of 837 publications were identified, with an average of 167 publications per year, most of which (66%) addressed the country’s priority health areas, and 58% had MakCHS faculty or students as first authors.

Conclusions
The research grants and publications at MakCHS are generally well-aligned with the Ugandan Health Ministry priorities. Greater efforts to establish centralized and efficient grants management procedures are needed. In addition, greater efforts are needed to expand capacity for MakCHS faculty leadership of grants, as well as to continue to expand the contribution of MakCHS faculty to lead research publications.
A grander challenge: the case of how Makerere University College of Health Sciences (MakCHS) contributes to health outcomes in Africa
Authors: Pariyo George , Serwadda David , Sewankambo Nelson K , Groves Sara , Bollinger Robert C , Peters David H 
Published: March 2011

Abstract

Background
“Grand challenges” in global health have focused on discovery and development of technologies to save lives. The “grander challenge” involves building institutions, systems, capacity and demand to effectively deliver strategies to improve health. In 2008, Makerere University began a radical institutional change to bring together four schools under one College of Health Sciences. This paper’s objective is to demonstrate how its leadership in training, research, and services can improve health in Uganda and internationally, which lies at the core of the College’s vision.

Methods
A comprehensive needs assessment involved five task forces that identified MakCHS’s contribution to the Ugandan government health priorities. Data were collected through analysis of key documents; systematic review of MakCHS publications and grants; surveys of patients, students and faculty; and key informant interviews of the College’s major stakeholders. Four pilot projects were conducted to demonstrate how the College can translate research into policy and practice, extend integrated outreach community-based education and service, and work with communities and key stakeholders to address their priority health problems.

Results
MakCHS inputs to the health sector include more than 600 health professionals graduating per year through 23 degree programs, many of whom assume leadership positions. MakCHS contributions to processes include strengthened approaches to engaging communities, standardized clinical care procedures, and evidence-informed policy development. Outputs include the largest number of outpatients and inpatient admissions in Uganda. From 2005-2009, MakCHS also produced 837 peer-reviewed research publications (67% in priority areas). Outcomes include an expanded knowledge pool, and contributions to coverage of health services and healthy behaviors. Impacts include discovery and applications of global significance, such as the use of nevirapine to prevent HIV transmission in childbirth and male circumcision for HIV prevention. Pilot projects have applied innovative demand and supply incentives to create a rapid increase in safe deliveries (3-fold increase after 3 months), and increased quality and use of HIV services with positive collateral improvements on non-HIV health services at community clinics.

Conclusion
MakCHS has made substantial contributions to improving health in Uganda, and shows great potential to enhance this in its new transformational role – a model for other Universities.
The organization and implementation of community-based education programs for health worker training institutions in Uganda
Authors: Kaye Dan , Mwanika Andrew , Burnham Gilbert , Chang Larry W , Mbalinda Scovia N , Okullo Isaac , Nabirye Rose C , Muhwezi Wilson , Oria Hussein , Kijjambu Stephen , Atuyambe Lynn , Aryeija Warren 
Published: March 2011

Abstract

Background
Community-based education (CBE) is part of the training curriculum for most health workers in Uganda. Most programs have a stated purpose of strengthening clinical skills, medical knowledge, communication skills, community orientation of graduates, and encouragement of graduates to work in rural areas. This study was undertaken to assess the scope and nature of community-based education for various health worker cadres in Uganda.

Methods
Curricula and other materials on CBE programs in Uganda were reviewed to assess nature, purpose, intended outcomes and evaluation methods used by CBE programs. In-depth and key informant interviews were conducted with people involved in managing CBE in twenty-two selected training institutions, as well as stakeholders from the community, Ministry of Health, Ministry of Education, civil society organizations and local government. Visits were made to selected sites where CBE training was conducted to assess infrastructure and learning resources being provided.

Results
The CBE curriculum is implemented in the majority of health training institutions in Uganda. CBE is a core course in most health disciplines at various levels – certificate, diploma and degree and for a range of health professionals. The CBE curriculum is systematically planned and implemented with major similarities among institutions. Organization, delivery, managerial strategies, and evaluation methods are also largely similar. Strengths recognized included providing hands-on experience, knowledge and skills generation and the linking learners to the communities. Almost all CBE implementing institutions cited human resource, financial, and material constraints.

Conclusions
The CBE curriculum is a widely used instructional model in Uganda for providing trainee health workers with the knowledge and skills relevant to meet community needs. Strategies to improve curricula and implementation concerns need further development. It is still uncertain whether this approach is increasing the number graduates seeking careers in rural health service, one of the stated program goals, an outcome which requires further study.
Artemisinin-induced parasite dormancy: a plausible mechanism for treatment failure
Authors: Codd Andrea , Teuscher Franka , Kyle Dennis E , Cheng Qin , Gatton Michelle L 
Published: March 2011

Abstract

Background
Artemisinin-combination therapy is a highly effective treatment for uncomplicated falciparum malaria but parasite recrudescence has been commonly reported following artemisinin (ART) monotherapy. The dormancy recovery hypothesis has been proposed to explain this phenomenon, which is different from the slower parasite clearance times reported as the first evidence of the development of ART resistance.

Methods
In this study, an existing P. falciparum infection model is modified to incorporate the hypothesis of dormancy. Published in vitro data describing the characteristics of dormant parasites is used to explore whether dormancy alone could be responsible for the high recrudescence rates observed in field studies using monotherapy. Several treatment regimens and dormancy rates were simulated to investigate the rate of clinical and parasitological failure following treatment.

Results
The model output indicates that following a single treatment with ART parasitological and clinical failures occur in up to 77% and 67% of simulations, respectively. These rates rapidly decline with repeated treatment and are sensitive to the assumed dormancy rate. The simulated parasitological and clinical treatment failure rates after 3 and 7 days of treatment are comparable to those reported from several field trials.

Conclusions
Although further studies are required to confirm dormancy in vivo, this theoretical study adds support for the hypothesis, highlighting the potential role of this parasite sub-population in treatment failure following monotherapy and reinforcing the importance of using ART in combination with other anti-malarials.
Assessment of global reporting of adverse drug reactions for anti-malarials, including artemisinin-based combination therapy, to the WHO Programme for International Drug Monitoring
Authors: Kuemmerle Andrea , Dodoo Alex NO , Olsson Sten , Van Erps Jan , Burri Christian , Lalvani Paul S 
Published: March 2011

Abstract

Background
In spite of enhanced control efforts, malaria remains a major public health problem causing close to a million deaths annually. With support from several donors, large amounts of artemisinin-based combination therapy (ACT) are being deployed in endemic countries raising safety concerns as little is known about the use of ACT in several of the settings where they are deployed. This project was undertaken to profile the provenance of the pharmacovigilance reporting of all anti-malarials, including ACT to the WHO adverse drug reaction (ADR) database (Vigibase™) over the past 40 years.

Methods
The WHO Programme for International Drug Monitoring, the Uppsala Monitoring Centre (UMC) provided anonymized extracts of Vigibase™ covering the period 1968-2008. All countries in the programme were clustered according to their malaria control phase and income status. The number of individual case safety reports (ICSRs) of anti-malarials was analyzed according to those clusters.

Results
From 1968 to 2008, 21,312 ICSRs suspecting anti-malarials were received from 64 countries. Low-income countries, that are also malaria-endemic (categorized as priority 1 countries) submitted only 1.2% of the ICSRs. Only 60 out of 21,312 ICSRs were related to ACT, 51 of which were coming from four sub-Saharan African countries. Although very few ICSRs involved artemisinin-based compounds, many of the adverse events reported were potentially serious.

Conclusions
This paper illustrates the low reporting of ADRs to anti-malarials in general and ACT in particular. Most reports were submitted by non-endemic and/or high-income countries. Given the current mix of large donor funding, the insufficient information on safety of these drugs, increasing availability of ACT and artemisinin-based monotherapies in public and private sector channels, associated potential for inappropriate use and finally a pipeline of more than 10 new novel anti-malarials in various stages of development, the presence of well functioning national pharmacovigilance systems is vital to ensure safe and responsible scale up of ACT deployment. Bringing together the competencies of national pharmacovigilance centres and various types of organizations in the NGO, academic and private sectors with global coordination to create short- and long-term solutions may help address the lag between rapidly growing ACT use and poor ADR reporting.
Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer
Authors: Cathcart Mary-Clare , Gately Kathy , Cummins Robert , Kay Elaine , O'Byrne Kenneth J , Pidgeon Graham P 
Published: March 2011

Abstract

Background
Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a survival factor in the disease.

Methods
TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall survival. Cell proliferation/survival and invasion was examined in NSCLC cells following both selective TXS inhibition and stable TXS over-expression.

Results
TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB2 levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient survival was observed. Selective TXS inhibition significantly reduced tumour cell growth and increased apoptosis, while TXS over-expression stimulated cell proliferation and invasiveness, and was protective against apoptosis.

Conclusion
TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC.
Mechanisms of oxysterol-induced carcinogenesis
Authors: Jusakul Apinya , Yongvanit Puangrat , Loilome Watcharin , Namwat Nisana , Kuver Rahul 
Published: March 2011

AbstractOxysterols are oxidation products of cholesterol that are generated by enzymatic reactions mediated by cytochrome P450 family enzymes or by non-enzymatic reactions involving reactive oxygen and nitrogen species. Oxysterols play various regulatory roles in normal cellular processes such as cholesterol homeostasis by acting as intermediates in cholesterol catabolism. Pathological effects of oxysterols have also been described, and various reports have implicated oxysterols in several disease states, including atherosclerosis, neurological disease, and cancer. Numerous studies show that oxysterols are associated with various types of cancer, including cancers of the colon, lung, skin, breast and bile ducts. The molecular mechanisms whereby oxysterols contribute to the initiation and progression of cancer are an area of active investigation. This review focuses on the current state of knowledge regarding the role of oxysterols in carcinogenesis. Mutagenicity of oxysterols has been described in both nuclear and mitochondrial DNA. Certain oxysterols such as cholesterol-epoxide and cholestanetriol have been shown to be mutagenic and genotoxic. Oxysterols possess pro-oxidative and pro-inflammatory properties that can contribute to carcinogenesis. Oxysterols can induce the production of inflammatory cytokines such as interleukin-8 and interleukin-1β. Certain oxysterols are also involved in the induction of cyclo-oxygenase-2 expression. Inflammatory effects can also be mediated through the activation of liver-X-receptor, a nuclear receptor for oxysterols. Thus, several distinct molecular mechanisms have been described showing that oxysterols contribute to the initiation and progression of cancers arising in various organ systems.
Characterization of proteome alterations in Phanerochaete chrysosporium in response to lead exposure
Authors: Yıldırım Volkan , Özcan Servet , Becher Dörte , Büttner Knut , Hecker Michael , Özcengiz Gülay 
Published: March 2011

Abstract

Background
Total soluble proteome alterations of white rot fungus Phanerochaete chrysosporium in response to different doses (25, 50 and 100 μM) of Pb (II) were characterized by 2DE in combination with MALDI-TOF-MS.

Results
Dose-dependent molecular response to Pb (II) involved a total of 14 up-regulated and 21 down-regulated proteins. The induction of an isoform of glyceraldehyde 3-phosphate dehydrogenase, alcohol dehydrogenase class V, mRNA splicing factor, ATP-dependent RNA helicase, thioredoxin reductase and actin required a Pb (II) dose of at least 50 μM. Analysis of the proteome dynamics of mid-exponential phase cells of P. chrysosporium subjected to 50 μM lead at exposure time intervals of 1, 2, 4 and 8 h, identified a total of 23 proteins in increased and 67 proteins in decreased amount. Overall, the newly induced/strongly up-regulated proteins involved in (i) amelioration of lipid peroxidation products, (ii) defense against oxidative damage and redox metabolism, (iii) transcription, recombination and DNA repair (iv) a yet unknown function represented by a putative protein.

Conclusion
The present study implicated the particular role of the elements of DNA repair, post-tanscriptional regulation and heterotrimeric G protein signaling in response to Pb (II) stress as shown for the first time for a basidiomycete.
Glutamate carboxypeptidase activity in human skin biopsies as a pharmacodynamic marker for clinical studies
Authors: Rojas Camilo , Stathis Marigo , Polydefkis Michael , Rudek Michelle A , Zhao Ming , Ebenezer Gigi J , Slusher Barbara S 
Published: March 2011

AbstractBackgroundGlutamate excitotoxicity is thought to be involved in the pathogenesis of neurodegenerative disease. One potential source of glutamate is N-acetyl-aspartyl-glutamate (NAAG) which is hydrolyzed to glutamate and N-acetyl-aspartate (NAA) in a reaction catalyzed by glutamate carboxypeptidase (GCP). As a result, GCP inhibition is thought to be beneficial for the treatment of neurodegenerative diseases where excess glutamate is presumed pathogenic. Both pharmacological and genetic inhibition of GCP has shown therapeutic utility in preclinical models and this has led to GCP inhibitors being pursued for the treatment of nervous system disorders in human clinical trials. Specifically, GCP inhibitors are currently being developed for peripheral neuropathy and neuropathic pain. The purpose of this study was to develop a pharmacodynamic (PD) marker assay to use in clinical development. The PD marker will determine the effect of GCP inhibitors on GCP enzymatic activity in human skin as measure of inhibition in peripheral nerve and help predict drug doses required to elicit pharmacologic responses.MethodsGCP activity was first characterized in both human skin and rat paw pads. GCP activity was then monitored in both rodent paw pads and sciatic nerve from the same animals following peripheral administration of various doses of GCP inhibitor. Significant differences among measurements were determined using two-tailed distribution, equal variance student's t test.ResultsWe describe for the first time, a direct and quantifiable assay to evaluate GCP enzymatic activity in human skin biopsy samples. In addition, we show that GCP activity in skin is responsive to pharmacological manipulation; GCP activity in rodent paws was inhibited in a dose response manner following peripheral administration of a potent and selective GCP inhibitor. Inhibition of GCP activity in rat paw pads was shown to correlate to inhibition of GCP activity in peripheral nerve.ConclusionMonitoring GCP activity in human skin after administration of GCP inhibitors could be readily used as PD marker in the clinical development of GCP inhibitors. Enzymatic activity provides a simple and direct measurement of GCP activity from tissue samples easily assessable in human subjects.
Field emission enhancement of Au-Si nano-particle-decorated silicon nanowires
Authors: Zhao Fei , Cheng Guo-an , Zheng Rui-ting , Zhao Dan-dan , Wu Shao-long , Deng Jian-hua 
Published: March 2011

AbstractAu-Si nano-particle-decorated silicon nanowire arrays have been fabricated by Au film deposition on silicon nanowire array substrates and then post-thermal annealing under hydrogen atmosphere. Field emission measurements illustrated that the turn-on fields of the non-annealed Au-coated SiNWs were 6.02 to 7.51 V/μm, higher than that of the as-grown silicon nanowires, which is about 5.01 V/μm. Meanwhile, after being annealed above 650°C, Au-Si nano-particles were synthesized on the top surface of the silicon nanowire arrays and the one-dimensional Au-Si nano-particle-decorated SiNWs had a much lower turn-on field, 1.95 V/μm. The results demonstrated that annealed composite silicon nanowire array-based electron field emitters may have great advantages over many other emitters.
The molecular dynamic simulation on impact and friction characters of nanofluids with many nanoparticles system
Authors: Lv Jizu , Bai Minli , Cui Wenzheng , Li Xiaojie 
Published: March 2011

AbstractImpact and friction model of nanofluid for molecular dynamics simulation was built which consists of two Cu plates and Cu-Ar nanofluid. The Cu-Ar nanofluid model consisted of eight spherical copper nanoparticles with each particle diameter of 4 nm and argon atoms as base liquid. The Lennard-Jones potential function was adopted to deal with the interactions between atoms. Thus motion states and interaction of nanoparticles at different time through impact and friction process could be obtained and friction mechanism of nanofluids could be analyzed. In the friction process, nanoparticles showed motions of rotation and translation, but effected by the interactions of nanoparticles, the rotation of nanoparticles was trapped during the compression process. In this process, agglomeration of nanoparticles was very apparent, with the pressure increasing, the phenomenon became more prominent. The reunited nanoparticles would provide supporting efforts for the whole channel, and in the meantime reduced the contact between two friction surfaces, therefore, strengthened lubrication and decreased friction. In the condition of overlarge positive pressure, the nanoparticles would be crashed and formed particles on atomic level and strayed in base liquid.
Growth of carbon nanowalls at atmospheric pressure for one-step gas sensor fabrication
Authors: Yu Kehan , Bo Zheng , Lu Ganhua , Mao Shun , Cui Shumao , Zhu Yanwu , Chen Xinqi , Ruoff Rodney S , Chen Junhong 
Published: March 2011

AbstractCarbon nanowalls (CNWs), two-dimensional "graphitic" platelets that are typically oriented vertically on a substrate, can exhibit similar properties as graphene. Growth of CNWs reported to date was exclusively carried out at a low pressure. Here, we report on the synthesis of CNWs at atmosphere pressure using "direct current plasma-enhanced chemical vapor deposition" by taking advantage of the high electric field generated in a pin-plate dc glow discharge. CNWs were grown on silicon, stainless steel, and copper substrates without deliberate introduction of catalysts. The as-grown CNW material was mainly mono- and few-layer graphene having patches of O-containing functional groups. However, Raman and X-ray photoelectron spectroscopies confirmed that most of the oxygen groups could be removed by thermal annealing. A gas-sensing device based on such CNWs was fabricated on metal electrodes through direct growth. The sensor responded to relatively low concentrations of NO2 (g) and NH3 (g), thus suggesting high-quality CNWs that are useful for room temperature gas sensors.PACS: Graphene (81.05.ue), Chemical vapor deposition (81.15.Gh), Gas sensors (07.07.Df), Atmospheric pressure (92.60.hv)