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The University of the Philippines Manila , founded in 1908, is a coeducational and public research university in the Philippines. It is located in the city of Manila, the country's capital. It is the oldest of the seven constituent universities of the University of the Philippines System. Its oldest degree-granting unit is the College of Medicine, which was founded in 1905 as the Philippine Medical School, predating the founding of U.P. by three years.It is the center of health science education in the country, with the establishment of the National Health science Center. It is also a reputable research center in the health science in the Asia-Pacific rim. It exercises administrative supervision over the Philippine General Hospital . U.P. Manila is a reputable school of tertiary learning in the health science, and more high school students interested in this field apply to it than to any other college or university in the country.As of 2001, the Commission on Higher Education of the Philippines has identified two centers of excellence in U.P. Manila. The COEs in the University are Medicine and Nursing, with the U.P. College of Medicine as the very first Center of Excellence in Medical Education in the Philippines. It is currently among only five medical institutions to be recognized as Centers of Excellence in Medical Education. Wikipedia.

Caoili S.E.C.,University of the Philippines at Manila
Immunome Research | Year: 2011

Global health must address a rapidly evolving burden of disease, hence the urgent need for versatile generic technologies exemplified by peptide-based vaccines. B-cell epitope prediction is crucial for designing such vaccines; yet this approach has thus far been largely unsuccessful, prompting further inquiry into the underlying reasons for its apparent inadequacy. Two major obstacles to the development of B-cell epitope prediction for peptide-based vaccine design are (1) the prevailing binary classification paradigm, which mandates the problematic dichotomization of continuous outcome variables, and (2) failure to explicitly model biological consequences of immunization that are relevant to practical considerations of safety and efficacy. The first obstacle is eliminated by redefining the predictive task as quantitative estimation of empirically observable biological effects of antibody-antigen binding, such that prediction is benchmarked using measures of correlation between continuous rather than dichotomous variables; but this alternative approach by itself fails to address the second obstacle even if benchmark data are selected to exclusively reflect functionally relevant cross-reactivity of antipeptide antibodies with protein antigens (as evidenced by antibody-modulated protein biological activity), particularly where only antibody-antigen binding is actually predicted as a surrogate for its biological effects. To overcome the second obstacle, the prerequisite is deliberate effort to predict, a priori, biological outcomes that are of immediate practical significance from the perspective of vaccination. This demands a much broader and deeper systems view of immunobiology than has hitherto been invoked for B-cell epitope prediction. Such a view would facilitate comprehension of many crucial yet largely neglected aspects of the vaccine-design problem. Of these, immunodominance among B-cell epitopes is a central unifying theme that subsumes immune phenomena of tolerance, imprinting and refocusing; but it is meaningful for vaccine design only in the light of disease-specific pathophysiology, which for infectious processes is complicated by host-pathogen coevolution. To better support peptide-based vaccine design, B-cell epitope prediction would entail individualized quantitative estimation of biological outcomes relevant to safety and efficacy. Passive-immunization experiments could serve as an important initial proving ground for B-cell epitope prediction en route to vaccine-design applications, by restricting biological complexity to render epitope-prediction problems more computationally tractable. © 2011 Caoili et al; licensee Nikolai Petrovsky Publishing.

Alejandria M.M.,University of the Philippines at Manila
The Cochrane database of systematic reviews | Year: 2013

Mortality from sepsis and septic shock remains high. Results of trials on intravenous immunoglobulins (IVIG) as adjunctive therapy for sepsis have been conflicting. This is an update of a Cochrane review that was originally published in 1999 and updated in 2002 and 2010. To estimate the effects of IVIG as adjunctive therapy in patients with bacterial sepsis or septic shock on mortality, bacteriological failure rates, and duration of stay in hospital. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 6), MEDLINE (1966 to December 2012), and EMBASE (1988 to December 2012). We contacted investigators in the field for unpublished data. The original search was performed in 1999 and updated in 2002 and 2008. We included randomized controlled trials comparing IVIG (monoclonal or polyclonal) with placebo or no intervention in patients of any age with bacterial sepsis or septic shock. Two authors independently assessed the studies for inclusion and undertook methodologic quality assessment and data abstraction. We conducted pre-specified subgroup analyses by type of immunoglobulin preparation. We included 43 studies that met our inclusion criteria in this updated review out of 88 potentially eligible studies. The studies included a large polyclonal IVIG trial in neonates that was concluded in 2011 and classified as ongoing in the 2010 version of this review. Pooled analysis of polyclonal and monoclonal IVIG was not done due to clinical heterogeneity. Subgroup analysis of 10 polyclonal IVIG trials (n = 1430) and seven trials on IgM-enriched polyclonal IVIG (n = 528) showed significant reductions in mortality in adults with sepsis compared to placebo or no intervention (relative risk (RR) 0.81; 95% confidence interval (CI) 0.70 to 0.93 and RR 0.66; 95% CI 0.51 to 0.85, respectively). Subgroup analysis of polyclonal IVIG in neonates, which now includes the recently concluded large polyclonal IVIG trial, showed no significant reduction in mortality for standard IVIG (RR 1.00; 95% CI 0.92 to 1.08; five trials, n = 3667) and IgM-enriched polyclonal IVIG (RR 0.57; 95% CI 0.31 to 1.04; three trials, n = 164). Sensitivity analysis of trials with low risk of bias showed no reduction in mortality with polyclonal IVIG in adults (RR 0.97; 95% CI 0.81 to 1.15; five trials, n = 945) and neonates (RR 1.01; 95% CI 0.93 to 1.09; three trials, n = 3561). Mortality was not reduced among patients (eight trials, n = 4671) who received anti-endotoxin antibodies (RR 0.99; 95% CI 0.91 to1.06) while anti-cytokines (nine trials, n = 7893) demonstrated a marginal reduction in mortality (RR 0.92; 95% CI 0.86 to 0.97). Polyclonal IVIG reduced mortality among adults with sepsis but this benefit was not seen in trials with low risk of bias. Among neonates with sepsis, there is sufficient evidence that standard polyclonal IVIG, as adjunctive therapy, does not reduce mortality based on the inclusion of the large polyclonal IVIG trial on neonates. For Ig-M enriched IVIG, the trials on neonates and adults were small and the totality of the evidence is still insufficient to support a robust conclusion of benefit. Adjunctive therapy with monoclonal IVIGs remains experimental.

Caoili S.E.C.,University of the Philippines at Manila
Methods in Molecular Biology | Year: 2014

Many computational approaches to B-cell epitope prediction have been published, including combinations of previously proposed methods, which complicates the tasks of further developing such computational approaches and of selecting those most appropriate for practical applications (e.g., the design of novel immunodiagnostics and vaccines). These tasks are considered together herein to clarify their close but often overlooked interrelationship, thereby providing a guide to their performance in mutual support of one another, with emphasis on key physicochemical and biological considerations that are relevant from an applications perspective. This aims to assist investigators in performing either or both tasks, with the overall goals of successfully applying computational tools towards practical ends and of generating informative new data towards iterative improvement of the tools, particularly as regards the design of peptide-based immunogens for eliciting the production of antipeptide antibodies that modulate biological activity of protein targets via functionally relevant cross-reactivity in relation to the phenomena of protein folding and protein disorder. © Springer Science+Business Media New York 2014.

FlorCruz N.V.,University of the Philippines at Manila
Cochrane database of systematic reviews (Online) | Year: 2012

Fungal keratitis is a fungal infection of the cornea. It is common in agricultural tropical countries but relatively uncommon in developed countries. Although there are medications available, their effectiveness is unclear. To examine the effect of different antifungal drugs in the management of fungal keratitis. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 8), MEDLINE (January 1950 to August 2011), EMBASE (January 1980 to August 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 29 August 2011. We included all relevant randomised controlled trials (RCTs) on medical therapy for fungal keratitis. Two review authors selected studies for inclusion into the review, assessed trials for risk of bias and extracted data. Interventions were compared by the proportions of participants that did not heal after a specific time of therapy. No meta-analysis was performed because the trials studied different medications with different concentrations. We included nine trials in this review; seven conducted in India, one in Bangladesh and one in Egypt. A total of 568 participants were randomised to the following comparisons: 1% topical itraconazole versus 1% topical itraconazole and oral itraconazole, different concentrations of silver sulphadiazine versus 1% miconazole, 1% silver sulphadiazine ointment versus 1% miconazole ointment, 2% econazole versus 5% natamycin, different concentrations of topical chlorhexidine gluconate versus 5% natamycin, 0.2% chlorhexidine gluconate versus 2.5% natamycin and voriconazole 1% versus natamycin 5%. The included trials were small and of variable quality. Differences between different regimens were not statistically different, which may reflect the low sample sizes. Based on the trials included in this review, there is no evidence to date that any particular drug, or combination of drugs, is more effective in the management of fungal keratitis. The trials included in this review were of variable quality and were generally underpowered.

Caoili S.E.C.,University of the Philippines at Manila
Journal of Immunological Methods | Year: 2015

A general framework is presented for predicting quantitative biological effects mediated by antipeptide antibodies, primarily on the basis of antigen structure (possibly featuring intrinsic disorder) analyzed to estimate epitope-paratope binding affinities, which in turn is considered within the context of dose-response relationships as regards antibody concentration. This is illustrated mainly using an approach based on protein structural energetics, whereby expected amounts of solvent-accessible surface area buried upon epitope-paratope binding are related to the corresponding binding affinity, which is estimated from putative B-cell epitope structure with implicit treatment of paratope structure, for antipeptide antibodies either reacting with peptides or cross-reacting with cognate protein antigens. Key methods described are implemented in SAPPHIRE/SUITE (Structural-energetic Analysis Program for Predicting Humoral Immune Response Epitopes/SAPPHIRE User Interface Tool Ensemble; publicly accessible via http://freeshell.de/~badong/suite.htm). Representative results thus obtained are compared with published experimental data on binding affinities and quantitative biological effects, with special attention to loss of paratope sidechain conformational entropy (neglected in previous analyses) and in light of key in-vivo constraints on antigen-antibody binding affinity and antibody-mediated effects. Implications for further refinement of B-cell epitope prediction methods are discussed as regards envisioned biomedical applications including the development of prophylactic and therapeutic antibodies, peptide-based vaccines and immunodiagnostics. © 2015 Elsevier B.V.

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