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Articles by Anderson López in JoVE

 JoVE Immunology and Infection

Cutaneous Leishmaniasis in the Dorsal Skin of Hamsters: a Useful Model for the Screening of Antileishmanial Drugs


JoVE 3533 4/21/2012

1Program for the Study and Control of Tropical Diseases -PECET-School of Medicine, University of Antioquia, 2School of Agrarian Sciences, University of Antioquia

Optimization of the experimental hamster model for cutaneous leishmaniasis by intradermal injection of Leishmania promastigotes at the dorsal skin. This approach is useful during inoculation, follow-up, characterization of lesions, application of treatments and obtaining of clinical samples. Locomotion, search for food and water, play and social activities are preserved.

Other articles by Anderson López on PubMed

Strengthening Evaluation to Capture the Breadth of Public Health Practice: Ideal Vs. Real

The Practice of Surrogacy in New Zealand

BACKGROUND: Commercial surrogacy is prohibited in New Zealand by the Human Assisted Reproductive Technology Act (HART Act). However, altruistic clinic-assisted surrogacy is permitted. Couples wishing to attempt altruistic surrogacy must apply for approval to a statutorily appointed ethics committee. One of seven principles that underpin the HART Act stipulates that the needs, values and beliefs of Maori (NZ's indigenous population) should be considered and treated with respect. AIM: This paper reviews the outcomes of surrogacy applications since the HART Act was established and the uptake of surrogacy by Maori. METHODS: The authors examined the demographic data provided to the ethics committee by way of surrogacy applications and the outcome data provided by fertility clinics. This paper reviews the outcomes for surrogacy applications: the number accepted/declined, the number of live births, those applications discontinued and uptake by Maori. RESULTS: Of 104 applications for surrogacy between 2005 and 2010, 4 (3.8%) were declined. By July 2011, of 100 approved, there have been 26 (26%) live births; 52 (52%) were discontinued, and 22 (22%) remain ongoing. Maori are much less likely to utilise surrogacy. Of the 104 original applications, 9 (8.6%) Maori women were willing to act as a surrogate, and 2 (1.9%) were intended mothers. 7 (6.7%) Maori were partners of a surrogate, with 2 (1.9%) intending mothers having Maori partners. CONCLUSIONS: The process of surrogacy applications is comprehensive and robust, resulting in few being declined. Further research is required to discover why applications are discontinued and why, despite explicit attempts to meet the needs of Maori, few utilise surrogacy.

A Distinct Lineage of Influenza A Virus from Bats

Influenza A virus reservoirs in animals have provided novel genetic elements leading to the emergence of global pandemics in humans. Most influenza A viruses circulate in waterfowl, but those that infect mammalian hosts are thought to pose the greatest risk for zoonotic spread to humans and the generation of pandemic or panzootic viruses. We have identified an influenza A virus from little yellow-shouldered bats captured at two locations in Guatemala. It is significantly divergent from known influenza A viruses. The HA of the bat virus was estimated to have diverged at roughly the same time as the known subtypes of HA and was designated as H17. The neuraminidase (NA) gene is highly divergent from all known influenza NAs, and the internal genes from the bat virus diverged from those of known influenza A viruses before the estimated divergence of the known influenza A internal gene lineages. Attempts to propagate this virus in cell cultures and chicken embryos were unsuccessful, suggesting distinct requirements compared with known influenza viruses. Despite its divergence from known influenza A viruses, the bat virus is compatible for genetic exchange with human influenza viruses in human cells, suggesting the potential capability for reassortment and contributions to new pandemic or panzootic influenza A viruses.

Evaluating and Giving Feedback to Mentors: New Evidence-based Approaches

A comprehensive mentoring program includes a variety of components. One of the most important is the ongoing assessment of and feedback to mentors. Scholars need strong active mentors who have the expertise, disposition, motivation, skills, and the ability to accept feedback and to adjust their mentoring style. Assessing the effectiveness of a given mentor is no easy task. Variability in learning needs and academic goals among scholars makes it difficult to develop a single evaluation instrument or a standardized procedure for evaluating mentors. Scholars, mentors, and program leaders are often reluctant to conduct formal evaluations, as there are no commonly accepted measures. The process of giving feedback is often difficult and there is limited empirical data on efficacy. This article presents a new and innovative six-component approach to mentor evaluation that includes the assessment of mentee training and empowerment, peer learning and mentor training, scholar advocacy, mentee-mentor expectations, mentor self-reflection, and mentee evaluation of their mentor.

Altered Expression of Mitochondrial Electron Transport Proteins and Improved Myocardial Energetic State During Late Ischemic Preconditioning

Background. Altered expression of mitochondrial electron transport proteins has been shown in preconditioned myocardial tissue. We wish to determine whether these alterations persist in the Second Window of Protection (SWOP) and if so, whether a favorable energetic state is facilitated during subsequent ischemia. Methods. Fourteen pigs underwent a SWOP protocol with ten 2-minute balloon inflations in the LAD artery, each separated by 2 minutes reperfusion. Twenty-four hours later, mitochondria were isolated from SWOP and SHAM pig hearts and analyzed for uncoupling protein (UCP)-2 content by western blot analysis, proteomic changes by iTRAQ® and respiration by an oxygen electrode. In parallel in vivo studies, high-energy nucleotides were obtained by transmural biopsy from anesthetized SWOP and SHAM pigs at baseline and during sustained low-flow ischemia. Results. Compared with SHAM mitochondria, ex vivo SWOP heart tissue demonstrated increased UCP-2 and a greater expression of complex IV (cytochrome c oxidase) and complex V (ATPase) proteins. In comparison with SHAM pigs during in vivo conditions, transmural energetics in SWOP hearts, as estimated by the free energy of ATP hydrolysis (ΔG(0)), were similar at baseline but decreased less by the end of low-flow ischemia (-57.0±2.1 versus -51.1±1.4 kJ/mol; P<0.05). Conclusions. Within isolated mitochondria from preconditioned SWOP hearts, UCP-2 is increased and in concert with enhanced Complex IV and V proteins, imparts a favorable energetic state during low-flow ischemia. These data support the notion that mitochondrial adaptations that may reduce oxidant damage do not reduce the overall efficiency of energetics during sustained oxygen deprivation.

Aging and Health in America: a Tale from Two Boomers

Aging in the United States: Opportunities and Challenges for Public Health

FOXA1 Represses the Molecular Phenotype of Basal Breast Cancer Cells

Breast cancer is a heterogeneous disease that comprises multiple subtypes. Luminal subtype tumors confer a more favorable patient prognosis, which is, in part, attributed to estrogen receptor (ER)-α positivity and antihormone responsiveness. Expression of the forkhead box transcription factor, FOXA1, similarly correlates with the luminal subtype and patient survival, but is also present in a subset of ER-negative tumors. FOXA1 is also consistently expressed in luminal breast cancer cell lines even in the absence of ER. In contrast, breast cancer cell lines representing the basal subtype do not express FOXA1. To delineate an ER-independent role for FOXA1 in maintaining the luminal phenotype, and hence a more favorable prognosis, we performed expression microarray analyses on FOXA1-positive and ER-positive (MCF7, T47D), or FOXA1-positive and ER-negative (MDA-MB-453, SKBR3) luminal cell lines in the presence or absence of transient FOXA1 silencing. This resulted in three FOXA1 transcriptomes: (1) a luminal signature (consistent across cell lines), (2) an ER-positive signature (restricted to MCF7 and T47D) and (3) an ER-negative signature (restricted to MDA-MB-453 and SKBR3). Gene set enrichment analyses revealed FOXA1 silencing causes a partial transcriptome shift from luminal to basal gene expression signatures. FOXA1 binds to a subset of both luminal and basal genes within luminal breast cancer cells, and loss of FOXA1 increases enhancer RNA transcription for a representative basal gene (CD58). These data suggest FOXA1 directly represses a subset of basal signature genes. Functionally, FOXA1 silencing increases migration and invasion of luminal cancer cells, both of which are characteristics of basal subtype cells. We conclude FOXA1 controls plasticity between basal and luminal breast cancer cells, not only by inducing luminal genes but also by repressing the basal phenotype, and thus aggressiveness. Although it has been proposed that FOXA1-targeting agents may be useful for treating luminal tumors, these data suggest that this approach may promote transitions toward more aggressive cancers.Oncogene advance online publication, 5 March 2012; doi:10.1038/onc.2012.62.

Anogenital Sweat Gland Adenocarcinoma of the Vulva: A Diagnostic Conundrum

Schistosoma Mansoni Histones: From Transcription to Chromatin Regulation; an in Silico Analysis

Schistosoma mansoni is a human endoparasite with a complex life cycle that also infects an invertebrate mollusk intermediate host and exhibits many diverse phenotypes. Its complexity is reflected in a large genome and different transcriptome profiles specific to each life cycle stage. Epigenetic regulation of gene expression such as the post-translational modification of histones has a significant impact on phenotypes, and this information storage function resides primarily at histone tails, which results in a varied histone code. Evidence of transcription of the different histone families at all life stages of the parasite was detected by a survey of transcriptome databases; manual curation of each gene prediction at the genome sequence level showed errors in the coding sequences of three of them. The biogenesis of histones is coupled to DNA replication, and a detailed in silico analysis of the specialized machinery of histone mRNA processing in the S. mansoni genome reveals that it is as conserved as in other eukaryotes, consisting in transcription factors and stem-loop binding proteins which recognize the stem loop structure at the histone mRNA 3'UTR. Histone modifying enzymes (HMEs) such as histone acetyltransferases, methyltransferases and deacetylases (HDACs) have been described in S. mansoni, and their potential as new therapeutic targets was evidenced with the apoptotic phenotype that resulted from HDAC inhibition. However, the overall regulation of transcription coupled with gene expression profiles correlated to histone modifications has not yet been characterized. Besides the interaction of HMEs with histones, many factors involved in cellular processes are known to bind to histones, and were identified here by an in silico analysis of the S. mansoni genome. Knowledge of the histone families opens up perspectives for further studies that will lead to a better identification of their post-translational modifications, their gene regulation and to the possible characterization of HMEs as targets for the development of new drugs.

Ingenol Mebutate Gel for Actinic Keratosis

Actinic keratosis is a common precursor to sun-related squamous-cell carcinoma. Treating actinic keratoses and the surrounding skin area (i.e., field therapy) can eradicate clinical and subclinical actinic keratoses. Topical field therapy currently requires weeks or months of treatment. We investigated the efficacy and safety of a new topical field therapy for actinic keratosis, ingenol mebutate gel (0.015% for face and scalp and 0.05% for trunk and extremities).

Stroke in South Asia: A Systematic Review of Epidemiologic Literature from 1980 to 2010

Background: Globally 15 million people have an acute stroke every year and one third of them die secondary to stroke events. Most research on stroke prevention and treatment is done in developed countries, yet more than 85% of strokes occur in developing countries. In particular, stroke remains an underrecognized cause of death and disability in South Asia. Methods: We conducted a systematic review to identify reliable and comparable epidemiological evidence on stroke in South Asia from 1980 to 2010. Publications were screened for eligibility to identify only population-based stroke studies. Results: Of the 71 studies retrieved, only 6 studies from South Asia gave us acceptable estimates of the burden of stroke. Population-based studies from South Asia have stroke prevalence in the range of 45-471 per 100,000. The age-adjusted incidence rate varied from approximately 145 per 100,000 to 262 per 100,000. Rural parts of South Asia have a lower stroke prevalence compared with urban areas. Conclusions: Our review highlights the paucity of research data in South Asia. This must be addressed in order to accurately determine the burden of stroke in South Asia, so that specific policy recommendations can be formulated to combat the stroke epidemic in this region.

Early Pregnancy Soluble E-selectin Concentrations and Risk of Preeclampsia

: Circulating biomarkers of endothelial dysfunction and inflammation are elevated in late pregnancy in women with preeclampsia. We examined plasma levels of inflammatory cytokines and adhesion molecules in early pregnancy, to assess their ability to predict preeclampsia.

Cultivating Quality: Early Postoperative Ambulation: Back to Basics

A quality improvement project increases postoperative ambulation and decreases patient complications.

Structural Modifications Modulate Stability of Glutathione-activated Arylated Diazeniumdiolate Prodrugs

JS-K, a diazeniumdiolate-based nitric oxide (NO)-releasing prodrug, is currently in late pre-clinical development as an anti-cancer drug candidate. This prodrug was designed to be activated by glutathione (GSH) to release NO. To increase the potency of JS-K, we are investigating the effect of slowing the reaction of the prodrugs with GSH. Herein, we report the effect of replacement of nitro group(s) by other electron-withdrawing group(s) in JS-K and its homo-piperazine analogues on GSH activation and the drugs' biological activity. We show that nitro-to-cyano substitution increases the half-life of the prodrug in the presence of GSH without compromising the compound's in vivo antitumor activity.

Care Planning for Children with Lower Limb Amputation

This article explores the pathways of care for children who undergo lower limb amputation, from pre-surgery to rehabilitation. The consequences of surgery are manifold, including that children and their families must cope with life with a disability, effects on mobility, greater demands on metabolic reserve, disfigurement, pain and discomfort. Care can be divided into multidisciplinary pre-operative, post-operative, mid-term rehabilitation, including prosthetic limb casting and fitting, and long-term rehabilitation over many weeks and years. The involvement of the multidisciplinary team as the child progresses is described. It is recommended that care should be co-ordinated by a nominated lead professional. Effective discharge planning is crucial to a successful transition home and continuing rehabilitation.

20 Years Later, Not Much Has Changed

Hospitalizations Associated With Influenza and Respiratory Syncytial Virus in the United States, 1993-2008

Background. Age-specific comparisons of influenza and respiratory syncytial virus (RSV) hospitalization rates can inform prevention efforts, including vaccine development plans. Previous US studies have not estimated jointly the burden of these viruses using similar data sources and over many seasons.Methods. We estimated influenza and RSV hospitalizations in 5 age categories (<1, 1-4, 5-49, 50-64, and ≥65 years) with data for 13 states from 1993-1994 through 2007-2008. For each state and age group, we estimated the contribution of influenza and RSV to hospitalizations for respiratory and circulatory disease by using negative binomial regression models that incorporated weekly influenza and RSV surveillance data as covariates.Results. Mean rates of influenza and RSV hospitalizations were 63.5 (95% confidence interval [CI], 37.5-237) and 55.3 (95% CI, 44.4-107) per 100000 person-years, respectively. The highest hospitalization rates for influenza were among persons aged ≥65 years (309/100000; 95% CI, 186-1100) and those aged <1 year (151/100000; 95% CI, 151-660). For RSV, children aged <1 year had the highest hospitalization rate (2350/100000; 95% CI, 2220-2520) followed by those aged 1-4 years (178/100000; 95% CI, 155-230). Age-standardized annual rates per 100000 person-years varied substantially for influenza (33-100) but less for RSV (42-77).Conclusions. Overall US hospitalization rates for influenza and RSV are similar; however, their age-specific burdens differ dramatically. Our estimates are consistent with those from previous studies focusing either on influenza or RSV. Our approach provides robust national comparisons of hospitalizations associated with these 2 viral respiratory pathogens by age group and over time.

Education and Information for Practicing School Nurses: Which Technology-Supported Resources Meet Their Needs?

School nurses care for children with a variety of health-related conditions and they need information about managing these conditions, which is accessible, current, and useful. The goal of this literature review was to gather and synthesize information on technology-supported resources and to determine which met the educational needs of school nurses. Successful online educational programs were interactive and self-directed. The most common barriers were lack of time to find educational information, lack of knowledge about computers, technology, the Internet and specific programs, and lack of administrative support from school officials to use technology to access information and evidence for practice. Recommendations for successful use of technology to meet practicing school nurse's educational needs are offered.

Do You Work in a Critical Care Unit South of the Tyne? If So, The Northern Regional Committee is Actively Seeking to Recruit YOU!

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