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Find video protocols related to scientific articles indexed in Pubmed.
Economics in the age of big data.
Science
PUBLISHED: 11-08-2014
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The quality and quantity of data on economic activity are expanding rapidly. Empirical research increasingly relies on newly available large-scale administrative data or private sector data that often is obtained through collaboration with private firms. Here we highlight some challenges in accessing and using these new data. We also discuss how new data sets may change the statistical methods used by economists and the types of questions posed in empirical research.
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Effect of seasonal variation on adult clinical laboratory parameters in Rwanda, Zambia, and Uganda: implications for HIV biomedical prevention trials.
PLoS ONE
PUBLISHED: 08-13-2014
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To investigate the effect of seasonal variation on adult clinical laboratory parameters in Rwanda, Zambia, and Uganda and determine its implications for HIV prevention and other clinical trials.
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p28, a truncated form of TR?1 regulates mitochondrial physiology.
FEBS Lett.
PUBLISHED: 05-14-2014
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We have previously identified in mitochondria two truncated forms of the T3 nuclear receptor TR?1, with molecular weights of 43kDa (p43) and 28kDa (p28) respectively located in the matrix and in the inner membrane. Previously, we have demonstrated that p43 stimulates mitochondrial transcription and protein synthesis in the presence of T3. Here we report that p28 is targeted into the organelle in a T3-dependent manner and displays an affinity for T3 higher than the nuclear receptor. We tried to generate mice overexpressing p28 using the human ?-skeletal actin promoter, however we found an early embryonic lethality that was probably linked to a transient expression of p28 in trophoblast giant cells. This could be partly explained by the observation that overexpression of p28 in human fibroblasts induced alterations of mitochondrial physiology.
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Home-based versus clinic-based care for patients starting antiretroviral therapy with low CD4? cell counts: findings from a cluster-randomized trial.
AIDS
PUBLISHED: 01-29-2014
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African health services have shortages of clinical staff. We showed previously, in a cluster-randomized trial, that a home-based strategy using trained lay-workers is as effective as a clinic-based strategy. It is not known whether home-based care is suitable for patients with advanced HIV disease.
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Improvement in asthma control and inflammation in children undergoing adenotonsillectomy.
Pediatr. Res.
PUBLISHED: 01-24-2014
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Observational studies suggest that asthma control improves after adenotonsillectomy, but longitudinal studies that correlate the effect of the procedure on the levels of biomarkers associated with airway inflammation are limited.
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Patient and physician perceptions of medicare reimbursement policy for blepharoplasty and blepharoptosis surgery.
Ophthalmology
PUBLISHED: 01-03-2014
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To describe patient preferences regarding payment for blepharoplasty and blepharoptosis repair and physician practices before and after the 2009 change in reimbursement for these 2 procedures by the Centers for Medicare and Medicaid Services (CMS).
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Impact of Co-Infections and BCG Immunisation on Immune Responses among Household Contacts of Tuberculosis Patients in a Ugandan Cohort.
PLoS ONE
PUBLISHED: 01-01-2014
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Tuberculosis incidence in resource poor countries remains high. We hypothesized that immune modulating co-infections such as helminths, malaria, and HIV increase susceptibility to latent tuberculosis infection (LTBI), thereby contributing to maintaining the tuberculosis epidemic.
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Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.
PLoS ONE
PUBLISHED: 01-01-2014
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In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda.
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Dynamic logistic regression model and population attributable fraction to investigate the association between adherence, missed visits and mortality: a study of HIV-infected adults surviving the first year of ART.
BMC Infect. Dis.
PUBLISHED: 08-12-2013
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Adherence is one of the most important determinants of viral suppression and drug resistance in HIV- infected people receiving antiretroviral therapy (ART).
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Prevalence, comorbidity and predictors of anxiety disorders in children and adolescents in rural north-eastern Uganda.
Child Adolesc Psychiatry Ment Health
PUBLISHED: 03-23-2013
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Child and adolescent anxiety disorders are the most prevalent form of childhood psychopathology. Research on child and adolescent anxiety disorders has predominantly been done in westernized societies. There is a paucity of data on the prevalence, comorbidity, and predictors of anxiety disorders in children and adolescents in non-western societies including those in sub-Saharan Africa. This paper investigates the prevalence, comorbidity, and predictors of anxiety disorders in children and adolescents in north-eastern Uganda.
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Novel off-target effect of tamoxifen--inhibition of acid ceramidase activity in cancer cells.
Biochim. Biophys. Acta
PUBLISHED: 03-21-2013
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Acid ceramidase (AC), EC 3.5.1.23, a lysosomal enzyme, catalyzes the hydrolysis of ceramide to constituent sphingoid base, sphingosine, and fatty acid. Because AC regulates the levels of pro-apoptotic ceramide and mitogenic sphingosine-1-phosphate, it is considered an apt target in cancer therapy. The present study reveals, for the first time, that the prominent antiestrogen, tamoxifen, is a pan-effective AC inhibitor in the low, single digit micromolar range, as demonstrated in a wide spectrum of cancer cell types, prostate, pancreatic, colorectal, and breast. Prostate cancer cells were chosen for the detailed investigations. Treatment of intact PC-3 cells with tamoxifen produced time- and dose-dependent inhibition of AC activity. Tamoxifen did not impact cell viability nor did it inhibit AC activity in cell-free assays. In pursuit of mechanism of action, we demonstrate that tamoxifen induced time-, as early as 5min, and dose-dependent, as low as 5?M, increases in lysosomal membrane permeability (LMP), and time- and dose-dependent downregulation of AC protein expression. Assessing various protease inhibitors revealed that a cathepsin B inhibitor blocked tamoxifen-elicited downregulation of AC protein; however, this action failed to restore AC activity unless assayed in a cell-free system at pH4.5. In addition, pretreatment with tamoxifen inhibited PC-3 cell migration. Toremifene, an antiestrogen structurally similar to tamoxifen, was also a potent inhibitor of AC activity. This study reveals a new, off-target action of tamoxifen that may be of benefit to enhance anticancer therapies that either incorporate ceramide or target ceramide metabolism.
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Prevalence and risk factors of depression in childhood and adolescence as seen in four districts of North-Eastern Uganda.
BMC Int Health Hum Rights
PUBLISHED: 03-15-2013
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Millions of African children are having to grow up under harsh and adverse psychosocial conditions but its not fully understood how this negative psychosocial environment is affecting their mental health. This paper examines the prevalence and risk factors of depression in childhood and adolescence as seen in a community sample derived from four disadvantaged districts in north-eastern Uganda.
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Trends in child mortality: a prospective, population-based cohort study in a rural population in south-west Uganda.
Paediatr Int Child Health
PUBLISHED: 03-15-2013
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Although there has been substantial global progress in decreasing child mortality over the past two decades, progress in sub-Saharan Africa has largely lagged behind. The temporal trends in child mortality and associated risk factors were investigated in a cohort of children in rural Uganda.
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Long-term consistent use of a vaginal microbicide gel among HIV-1 sero-discordant couples in a phase III clinical trial (MDP 301) in rural south-west Uganda.
Trials
PUBLISHED: 01-21-2013
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A safe and effective vaginal microbicide could substantially reduce HIV acquisition for women. Consistent gel use is, however, of great importance to ensure continued protection against HIV infection, even with a safe and effective microbicide. We assessed the long-term correlates of consistent gel use in the MDP 301 clinical trial among HIV-negative women in sero-discordant couples in south-west Uganda.
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Tamoxifen magnifies therapeutic impact of ceramide in human colorectal cancer cells independent of p53.
Biochem. Pharmacol.
PUBLISHED: 01-16-2013
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Poor prognosis in patients with later stage colorectal cancer (CRC) necessitates the search for new treatment strategies. Ceramide, because of its role in orchestrating death cascades in cancer cells, is a versatile alternative. Ceramide can be generated by exposure to chemotherapy or ionizing radiation, or it can be administered in the form of short-chain analogs (C6-ceramide). Because intracellular P-glycoprotein (P-gp) plays a role in catalyzing the conversion of ceramide to higher sphingolipids, we hypothesized that administration of P-gp antagonists with C6-ceramide would magnify cell death cascades. Human CRC cell lines were employed, HCT-15, HT-29, and LoVo. The addition of either tamoxifen, VX-710, verapamil, or cyclosporin A, antagonists of P-gp, enhanced C6-ceramide cytotoxicity in all cell lines. In depth studies with C6-ceramide and tamoxifen in LoVo cells showed the regimen induced PARP cleavage, caspase-dependent apoptosis, mitochondrial membrane permeabilization (MMP), and cell cycle arrest at G1 and G2. At the molecular level, the regimen, but not single agents, induced time-dependent upregulation of tumor suppressor protein p53; however, introduction of a p53 inhibitor staved neither MMP nor apoptosis. Nanoliposomal formulations of C6-ceramide and tamoxifen were also effective, yielding synergistic cell kill. We conclude that tamoxifen is a favorable adjuvant for enhancing C6-ceramide cytotoxicity in CRC, and demonstrates uniquely integrated effects. The high frequency of expression of P-gp in CRC presents an adventitious target for complementing ceramide-based therapies, a strategy that could hold promise for treatment of resistant disease.
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Mice lacking the p43 mitochondrial T3 receptor become glucose intolerant and insulin resistant during aging.
PLoS ONE
PUBLISHED: 01-01-2013
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Thyroid hormones (TH) play an important regulatory role in energy expenditure regulation and are key regulators of mitochondrial activity. We have previously identified a mitochondrial triiodothyronine (T3) receptor (p43) which acts as a mitochondrial transcription factor of the organelle genome, which leads in vitro and in vivo, to a stimulation of mitochondrial biogenesis. Recently, we generated mice carrying a specific p43 invalidation. At 2 months of age, we reported that p43 depletion in mice induced a major defect in insulin secretion both in vivo and in isolated pancreatic islets, and a loss of glucose-stimulated insulin secretion. The present study was designed to determine whether p43 invalidation influences life expectancy and modulates blood glucose and insulin levels as well as glucose tolerance or insulin sensitivity during aging. We report that from 4 months old onwards, mice lacking p43 are leaner than wild-type mice. p43-/- mice also have a moderate reduction of life expectancy compared to wild type. We found no difference in blood glucose levels, excepted at 24 months old where p43-/- mice showed a strong hyperglycemia in fasting conditions compared to controls animals. However, the loss of glucose-stimulated insulin secretion was maintained whatever the age of mice lacking p43. If up to 12 months old, glucose tolerance remained unchanged, beyond this age p43-/- mice became increasingly glucose intolerant. In addition, if up to 12 months old p43 deficient animals were more sensitive to insulin, after this age we observed a loss of this capacity, culminating in 24 months old mice with a decreased sensitivity to the hormone. In conclusion, we demonstrated that during aging the depletion of the mitochondrial T3 receptor p43 in mice progressively induced an increased glycemia in the fasted state, glucose intolerance and an insulin-resistance several features of type-2 diabetes.
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Depletion of the p43 mitochondrial T3 receptor in mice affects skeletal muscle development and activity.
FASEB J.
PUBLISHED: 11-22-2011
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In vertebrates, skeletal muscle myofibers display different contractile and metabolic properties associated with different mitochondrial content and activity. We have previously identified a mitochondrial triiodothyronine receptor (p43) regulating mitochondrial transcription and mitochondrial biogenesis. When overexpressed in skeletal muscle, it increases mitochondrial DNA content, stimulates mitochondrial respiration, and induces a shift in the metabolic and contractile features of muscle fibers toward a slower and more oxidative phenotype. Here we show that a p43 depletion in mice decreases mitochondrial DNA replication and respiratory chain activity in skeletal muscle in association with the induction of a more glycolytic muscle phenotype and a decrease of capillary density. In addition, p43(-/-) mice displayed a significant increase in muscle mass relative to control animals and had an improved ability to use lipids. Our findings establish that the p43 mitochondrial receptor strongly affects muscle mass and the metabolic and contractile features of myofibers and provides evidence that this receptor mediates, in part, the influence of thyroid hormone in skeletal muscle.
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Contribution of population factors to estimation of human immunodeficiency virus prevalence trends: a cohort study in rural Uganda, 1989-2007.
Am. J. Epidemiol.
PUBLISHED: 10-14-2011
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Because the incidence of human immunodeficiency virus (HIV) infection is difficult to measure directly, prevalence trends often serve to track epidemiologic changes. Adult HIV prevalence in open population cohort studies, however, reflects changes in incidence, population factors (migration, deaths, and aging), and survey coverage. Data from an open cohort in rural Uganda enabled estimation of the contribution of these factors to prevalence trends from 1989 to 2007. New infections within this cohort represented on average 44% of new prevalent cases per year. Other factors affecting changes in prevalence included migration and death. Migrants and mobile people (those who leave and return to the study area) are in a higher-risk group and thus can affect prevalence trends. Incidence of HIV infection among mobile people was 2-4 times greater than among stable residents. The importance of mortality is shown by the rise in prevalence from 6.8% in 2005 to 7.4% in 2007, which was accompanied by a fall in mortality among HIV-infected participants (8.7% of HIV-infected in 2005, 5.2% in 2006, and 4.3% in 2007). Assessing HIV epidemic trends through prevalence requires consideration of population factors. Measuring HIV incidence directly remains the most accurate measure of trends with which to monitor the effect of intervention activities and should complement strategies such as national prevalence surveys.
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Primary prophylaxis of cryptococcal disease with fluconazole in HIV-positive Ugandan adults: a double-blind, randomised, placebo-controlled trial.
Lancet Infect Dis
PUBLISHED: 10-06-2011
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Cryptococcal disease remains an important cause of morbidity and mortality in HIV-infected individuals in sub-Saharan Africa, despite the introduction of antiretroviral therapy. We studied fluconazole as primary prophylaxis against cryptococcal disease in patients awaiting or starting antiretroviral therapy in Uganda.
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Mitochondrial T3 receptor p43 regulates insulin secretion and glucose homeostasis.
FASEB J.
PUBLISHED: 09-13-2011
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Thyroid hormone is a major determinant of energy expenditure and a key regulator of mitochondrial activity. We have previously identified a mitochondrial triiodothyronine receptor (p43) that acts as a mitochondrial transcription factor of the organelle genome, which leads, in vitro and in vivo, to a stimulation of mitochondrial biogenesis. Here we generated mice specifically lacking p43 to address its physiological influence. We found that p43 is required for normal glucose homeostasis. The p43(-/-) mice had a major defect in insulin secretion both in vivo and in isolated pancreatic islets and a loss of glucose-stimulated insulin secretion. Moreover, a high-fat/high-sucrose diet elicited more severe glucose intolerance than that recorded in normal animals. In addition, we observed in p43(-/-) mice both a decrease in pancreatic islet density and in the activity of complexes of the respiratory chain in isolated pancreatic islets. These dysfunctions were associated with a down-regulation of the expression of the glucose transporter Glut2 and of Kir6.2, a key component of the K(ATP) channel. Our findings establish that p43 is an important regulator of glucose homeostasis and pancreatic ?-cell function and provide evidence for the first time of a physiological role for a mitochondrial endocrine receptor.
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Examining the components of population-level sexual behavior trends from 1993 to 2007 in an open ugandan cohort.
Sex Transm Dis
PUBLISHED: 08-17-2011
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Sexual behavior changes are widely cited as contributing factors to sexually transmitted disease trends. We explore a rarely examined aspect of behavior trends in an open cohort--the relative impact of individuals changing reported behavior versus new responses due to a changing respondent base.
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Mortality in an antiretroviral therapy programme in Jinja, south-east Uganda: a prospective cohort study.
AIDS Res Ther
PUBLISHED: 05-27-2011
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There have been few reports of long-term survival of HIV-infected patients on antiretroviral therapy (ART) in Africa managed under near normal health service conditions.
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Prevalence and incidence of HIV in a rural community-based HIV vaccine preparedness cohort in Masaka, Uganda.
PLoS ONE
PUBLISHED: 05-07-2011
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Local HIV epidemiology data are critical in determining the suitability of a population for HIV vaccine efficacy trials. The objective of this study was to estimate the prevalence and incidence of, and determine risk factors for HIV transmission in a rural community-based HIV vaccine preparedness cohort in Masaka, Uganda.
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In utero and intra-partum HIV-1 transmission and acute HIV-1 infection during pregnancy: using the BED capture enzyme-immunoassay as a surrogate marker for acute infection.
Int J Epidemiol
PUBLISHED: 04-05-2011
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The BED assay was developed to estimate the proportion of recent HIV infections in a population. We used the BED assay as a proxy for acute infection to quantify the associated risk of mother-to-child-transmission (MTCT) during pregnancy and delivery. Design A total of 3773 HIV-1 sero-positive women were tested within 96 h of delivery using the BED assay, and CD4 cell count measurements were taken. Mothers were classified according to their likelihood of having recently seroconverted.
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Decreasing trends of bacteraemia among HIV-infected Ugandan adults: incidence, aetiology, clinical outcomes and effect of antiretroviral therapy in a semi-urban setting (2000-2008).
Trop. Med. Int. Health
PUBLISHED: 03-09-2011
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To investigate the effect of antiretroviral therapy on trends of incidence, aetiology and clinical outcomes of bacteraemia among HIV-infected Ugandans in a semi-urban setting.
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Clustering based on adherence data.
Epidemiol Perspect Innov
PUBLISHED: 03-08-2011
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Adherence to a medical treatment means the extent to which a patient follows the instructions or recommendations by health professionals. There are direct and indirect ways to measure adherence which have been used for clinical management and research. Typically adherence measures are monitored over a long follow-up or treatment period, and some measurements may be missing due to death or other reasons. A natural question then is how to describe adherence behavior over the whole period in a simple way. In the literature, measurements over a period are usually combined just by using averages like percentages of compliant days or percentages of doses taken. In the paper we adapt an approach where patient adherence measures are seen as a stochastic process. Repeated measures are then analyzed as a Markov chain with finite number of states rather than as independent and identically distributed observations, and the transition probabilities between the states are assumed to fully describe the behavior of a patient. The patients can then be clustered or classified using their estimated transition probabilities. These natural clusters can be used to describe the adherence of the patients, to find predictors for adherence, and to predict the future events. The new approach is illustrated and shown to be useful with a simple analysis of a data set from the DART (Development of AntiRetroviral Therapy in Africa) trial in Uganda and Zimbabwe.
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Adolescent suicidality as seen in rural northeastern Uganda: prevalence and risk factors.
Crisis
PUBLISHED: 03-05-2011
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Suicidal behavior in adolescence is a public health concern and has serious consequences for adolescents and their families. There is, however, a paucity of data on this subject from sub-Saharan Africa, hence the need for this study.
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Effectiveness of the standard WHO recommended retreatment regimen (category II) for tuberculosis in Kampala, Uganda: a prospective cohort study.
PLoS Med.
PUBLISHED: 02-07-2011
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Each year, 10%-20% of patients with tuberculosis (TB) in low- and middle-income countries present with previously treated TB and are empirically started on a World Health Organization (WHO)-recommended standardized retreatment regimen. The effectiveness of this retreatment regimen has not been systematically evaluated.
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War related sexual violence and its medical and psychological consequences as seen in Kitgum, Northern Uganda: A cross-sectional study.
BMC Int Health Hum Rights
PUBLISHED: 11-10-2010
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Despite the recent adoption of the UN resolution 1820 (2008) which calls for the cessation of war related sexual violence against civilians in conflict zones, Africa continues to see some of the worst cases of war related sexual violence including the mass sexual abuse of entire rural communities particularly in the Great Lakes region. In addition to calling for a complete halt to this abuse, there is a need for the systematic study of the reproductive, surgical and psychological effects of war related sexual violence in the African socio-cultural setting.This paper examines the specific long term health consequences of war related sexual violence among rural women living in two internally displaced persons camps in Kitgum district in war affected Northern Uganda who accessed the services of an Isis-Womens International Cross Cultural Exchange (Isis-WICCE) medical intervention.
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Barriers to starting ART and how they can be overcome: individual and operational factors associated with early and late start of treatment.
Trop. Med. Int. Health
PUBLISHED: 10-20-2010
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Despite expanding access to antiretroviral therapy (ART) in Sub-Saharan Africa, there are few data on patients perceptions about starting ART to explore issues affecting decisions to start ART in eligible individuals during the ART roll out.
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Factors associated with consistent condom use among rural young women in South Africa.
AIDS Care
PUBLISHED: 08-24-2010
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Despite high levels of awareness of HIV, condom use, particularly consistent use, is suboptimal among young South African women. This paper aims to investigate the factors associated with both any condom use and consistent use by young rural women. In this study 1204 sexually active female volunteers, aged 15-26 years, were selected using a two-stage procedure in which firstly 70 clusters were selected and thereafter up to 20 women per cluster were selected, to participate in a cluster randomised controlled trial of an HIV behavioural intervention. This study is analysing cross-sectional data from a baseline survey thus no causal inferences can be drawn. A structured questionnaire was administered at a baseline interview. An estimated 19.9% of young women reported consistent condom use in the 12 months before the interview, while 44.5% reported inconsistent use. Any condom use was associated with higher condom use self-efficacy (adjusted odds ratio (aOR) 1.59; 95% CI 1.41, 1.77), less association of trust with suggested condom use (aOR 0.86; 95% CI 0.82, 0.91), knowing ones HIV status (aOR 2.86; 95% CI 1.52, 5.39) and having a more educated mother (aOR 1.71; 95% CI 1.26, 2.33). Having had just one partner was associated with a lesser likelihood of any condom use (aOR 0.14; 95% CI 0.10, 0.20). Consistent use, compared with inconsistent use, was associated with having just one partner (aOR 3.25; 95% CI 2.23, 4.73), less relationship conflict (aOR 0.84; 95% CI 0.75, 0.91) and higher gender equity in relationships with a male partner (aOR 1.43; 95% CI 1.15, 1.77). Our findings suggest that gender equity, monogamy and harmonious relationships play a positive role in enabling women to reduce their risk for HIV infection. Such aspects of relationship context could form a significant part of the progressive strategies required for HIV-prevention interventions to be successful.
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Comparison of home and clinic-based HIV testing among household members of persons taking antiretroviral therapy in Uganda: results from a randomized trial.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-18-2010
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Due to high rates of undiagnosed and untreated HIV infection in Africa, we compared HIV counseling and testing (VCT) uptake among household members of patients receiving antiretroviral therapy.
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Operational evaluation of a service for prevention of mother-to-child transmission of HIV in rural Uganda: barriers to uptake of single-dose nevirapine and the role of birth reporting.
Trop. Med. Int. Health
PUBLISHED: 07-30-2010
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To determine factors associated with pregnant women being HIV positive, barriers to the uptake of single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission (PMTCT) and feasibility and effectiveness of reporting HIV-exposed infants born in facilities with no PMTCT services so as to receive NVP.
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Symptom burden in HIV-infected adults at time of HIV diagnosis in rural Uganda.
J Palliat Med
PUBLISHED: 04-14-2010
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This study aimed to measure symptom burden prior to antitetroviral therapy (ART) initiation in a population of adults with low CD4 presenting for human immunodeficiency virus (HIV) care and treatment in Uganda, and to explore the relationship between World Health Organization (WHO) stage, CD4 count, and symptomatology.
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Significantly diminished long-term specificity of the BED capture enzyme immunoassay among patients with HIV-1 with very low CD4 counts and those on antiretroviral therapy.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 03-23-2010
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To estimate the proportion who test as recent infections by the BED capture enzyme immunoassay (BED) among patients about to commence, and those receiving, antiretroviral therapy.
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Rates of virological failure in patients treated in a home-based versus a facility-based HIV-care model in Jinja, southeast Uganda: a cluster-randomised equivalence trial.
Lancet
PUBLISHED: 11-24-2009
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Identification of new ways to increase access to antiretroviral therapy in Africa is an urgent priority. We assessed whether home-based HIV care was as effective as was facility-based care.
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Haematological and biochemistry laboratory abnormalities associated with splenomegaly in asymptomatic adults in Masaka, Uganda: implications for HIV biomedical prevention trials.
Trop. Med. Int. Health
PUBLISHED: 11-23-2009
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To assess the degree of haematological and biochemistry abnormalities associated with splenomegaly in asymptomatic adults in order to determine whether they may be eligible for inclusion in HIV biomedical prevention trials.
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Mortality and loss-to-follow-up during the pre-treatment period in an antiretroviral therapy programme under normal health service conditions in Uganda.
BMC Public Health
PUBLISHED: 05-25-2009
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In many HIV programmes in Africa, patients are assessed clinically and prepared for antiretroviral treatment over a period of 4-12 weeks. Mortality rates following initiation of ART are very high largely because patients present late with advanced disease. The rates of mortality and retention during the pre-treatment period are not well understood. We conducted an observational study to determine these rates.
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Toward a 21st-century health care system: recommendations for health care reform.
Ann. Intern. Med.
PUBLISHED: 03-02-2009
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The coverage, cost, and quality problems of the U.S. health care system are evident. Sustainable health care reform must go beyond financing expanded access to care to substantially changing the organization and delivery of care. The FRESH-Thinking Project (www.fresh-thinking.org) held a series of workshops during which physicians, health policy experts, health insurance executives, business leaders, hospital administrators, economists, and others who represent diverse perspectives came together. This group agreed that the following 8 recommendations are fundamental to successful reform: 1. Replace the current fee-for-service payment system with a payment system that encourages and rewards innovation in the efficient delivery of quality care. The new payment system should invest in the development of outcome measures to guide payment. 2. Establish a securely funded, independent agency to sponsor and evaluate research on the comparative effectiveness of drugs, devices, and other medical interventions. 3. Simplify and rationalize federal and state laws and regulations to facilitate organizational innovation, support care coordination, and streamline financial and administrative functions. 4. Develop a health information technology infrastructure with national standards of interoperability to promote data exchange. 5. Create a national health database with the participation of all payers, delivery systems, and others who own health care data. Agree on methods to make de-identified information from this database on clinical interventions, patient outcomes, and costs available to researchers. 6. Identify revenue sources, including a cap on the tax exclusion of employer-based health insurance, to subsidize health care coverage with the goal of insuring all Americans. 7. Create state or regional insurance exchanges to pool risk, so that Americans without access to employer-based or other group insurance could obtain a standard benefits package through these exchanges. Employers should also be allowed to participate in these exchanges for their employees coverage. 8. Create a health coverage board with broad stakeholder representation to determine and periodically update the affordable standard benefit package available through state or regional insurance exchanges.
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Willingness to participate in preventive HIV vaccine trials in a community-based cohort in south western Uganda.
Trop. Med. Int. Health
PUBLISHED: 01-15-2009
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To assess willingness to participate in HIV vaccine trials and possible barriers to participation.
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Differential effects of acute cocaine and placebo administration on visual cortical activation in healthy subjects measured using BOLD fMRI.
Pharmacol. Biochem. Behav.
PUBLISHED: 01-14-2009
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Many blood oxygenation level dependent (BOLD) functional magnetic resonance imaging studies have shown a strong response due to cocaine in brain regions with high concentrations of dopamine receptors. However, cocaine also has non-specific effects, including cardiovascular changes that may cause changes in BOLD signals, raising the possibility that measured changes could be due to these non-specific effects. The following experiment was conducted to address this concern. Subjects were given either cocaine or saline infusions during a long BOLD functional magnetic resonance imaging study. A flashing uniform-field stimulus, periodically alternating between on and off, provided a strong activation of primary visual cortex. There was a significant main effect of drug between cocaine and placebo. Although we did not demonstrate a significant drug x time interaction, BOLD signal changes associated with visual stimulation appeared unchanged after cocaine administration, whereas the signal differences appeared to decrease during placebo. Explanation of the differential response between the two groups may reflect cocaine expectancy instead of a direct effect of cocaine on BOLD signal changes but will require further investigation to fully elucidate.
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Potential role of acid ceramidase in conversion of cytostatic to cytotoxic end-point in pancreatic cancer cells.
Cancer Chemother. Pharmacol.
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Acid ceramidase (AC) occupies an important place in the control of cancer cell proliferation. We tested the influence of AC inhibition on the effects of PSC 833, a P-glycoprotein antagonist with potent ceramide-generating capacity, to determine whether AC could be a therapeutic target in pancreatic cancer.
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HIV-1 subtype distribution trends and evidence of transmission clusters among incident cases in a rural clinical cohort in southwest Uganda, 2004-2010.
AIDS Res. Hum. Retroviruses
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The high diversity of HIV-1 has been shown to affect disease progression, transmission, and response to antiretroviral therapy and may influence HIV vaccine design. We describe the distribution trends of HIV-1 subtypes over a 7-year period among incident cases in a rural clinical cohort in Southwest Uganda and identify transmission clusters. Viral RNA was extracted from cryopreserved plasma samples from 94 participants who seroconverted and enrolled between 2004 and 2010. Partial gag (p24) and env (gp41) genes were directly sequenced to identify subtypes and transmission clusters with more than 95% bootstrap values. Direct sequencing of the partial pol gene and use of individual participant sexual life histories were also used to confirm these transmission clusters. The overall gag/env subtype distribution was A 28% (n=26), C 1% (n=1), and D 45% (n=42) and 27% (n=25) were intergene unique recombinant forms. The proportions of subtype A, D, or recombinants showed no significant increasing or decreasing trend over this time period (p=0.51). Phylogenetic analysis of the three genes confirmed 13 transmission clusters of which seven clusters were confirmed sexual partners using individual participants sexual life histories. Subtype D has remained the predominant subtype in this population. From 2004 to 2010, there was no change in the proportions of these subtypes. Phylogenetic analysis and participants sexual life histories revealed several transmission clusters. The high proportion of transmission clusters observed suggests continued high-risk sexual behavior and mixing in some individuals and possibly super transmitters in this presumed low-risk cohort, but also indicates that many transmissions occur in early HIV infection. This calls for early and targeted effective prevention and treatment intervention in this population.
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Ceramide--antiestrogen nanoliposomal combinations--novel impact of hormonal therapy in hormone-insensitive breast cancer.
Mol. Cancer Ther.
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Although the sphingolipid ceramide exhibits potent tumor suppressor effects, efforts to harness this have been hampered by poor solubility, uptake, bioavailability, and metabolic conversion. Therefore, identification of avenues to improve efficacy is necessary for development of ceramide-based therapies. In this study, we used mutant p53, triple-negative breast cancer (TNBC) cells, a type of breast cancer highly refractory to treatment, and cell-permeable nanoliposomal C6-ceramide in conjunction with the antiestrogen tamoxifen, which has been shown to be an effective modulator of ceramide metabolism. We show for the first time that nanoliposomal tamoxifen enhances nanoliposomal C6-ceramide cytotoxicity in cultured TNBC cells, a response that was accompanied by induction of cell-cycle arrest at G(1) and G(2), caspase-dependent induction of DNA fragmentation, and enhanced mitochondrial and lysosomal membrane permeability at 18 and 2 hours, respectively. Tamoxifen metabolites were also effective. Only tamoxifen promoted lysosomal membrane permeability. In addition, we show for the first time that tamoxifen inhibits acid ceramidase, as measured in intact cell assays; this effect was irreversible. Together, our findings show that tamoxifen magnifies the antiproliferative effects of C6-ceramide via combined targeting of cell-cycle traverse and lysosomal and mitochondrial integrity. We adduce that C6-ceramide-induced apoptosis is amplified by tamoxifens impact on lysosomes and perhaps accompanying inhibition of acid ceramidase, which could result in decreased levels of sphingosine 1-phosphate. This drug regimen could serve as a promising therapy for chemoresistant and triple-negative types of breast cancer, and thus represents an indication for tamoxifen, irrespective of estrogen receptor status.
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Mortality of HIV-infected and uninfected children in a longitudinal cohort in rural south-west Uganda during 8 years of follow-up.
Trop. Med. Int. Health
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To determine the impact of HIV on child mortality and explore potential risk factors for mortality among HIV-infected and HIV-exposed uninfected children in a longitudinal cohort in rural Uganda.
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Protein sequences involved in the mitochondrial import of the 3,5,3-L-triiodothyronine receptor p43.
J. Cell. Physiol.
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The major effect of T3 on mitochondrial activity has been partly explained by the discovery of p43, a T3-dependent transcription factor of the mitochondrial genome. P43 is imported into mitochondria in an atypical manner which is not yet fully understood. Our aim was to characterize the p43 sequences inducing its mitochondrial import, using in organello import experiments with wild-type or mutated proteins and validation in CV1 cells. We find that several sequences define the mitochondrial addressing. Two alpha helices in the C-terminal part of p43 are actual mitochondrial import sequences as fusion to a cytosolic protein induces its mitochondrial translocation. Helix 5 drives the atypical mitochondrial import process, whereas helices 10/11 induce a classical import process. However, despite its inability to drive a mitochondrial import, the N-terminal region of p43 also plays a permissive role as in the presence of the C-terminal import sequences different N-terminal regions determine whether the protein is imported or not. These results can be extrapolated to other mitochondrial proteins related to the nuclear receptor superfamily, devoid of classical mitochondrial import sequences.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.