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Este artículo presenta algunos resultados obtenidos a partir de la sistematización de los insumos de la vivencia escolar de IV semestre (práctica docente), durante los años 2003 (primer semestre), al 2006 (segundo semestre), en la Licenciatura de Pedagogía Infantil de la Facultad de Ciencias y Educación de la Universidad Distrital Francisco José de Caldas, Bogotá, Colombia. El propósito de la presente investigación, es aproximarse o lograr que los estudiantes de cuarto semestre capten el significado de los conceptos «artefacto cultural» y «pensar tecnológicamente» para que puedan dotar de sentido la actividad pedagógica que realizan con los niños de 4 a 6 años promedio. Se hace énfasis en la ficha cualitativa como herramienta etnográfica, donde el resultado de ésta es una propuesta metodológica estructurada y afinada para el aula universitaria.

Introduction and Objectives: Bipolar disorder (BD) has been related to various cognitive dysfunctions as well as to a high prevalence of metabolic syndrome (MS), which seems to influence the cognitive performance of patients with BD. Therefore, different hypotheses have been generated to try to explain the pathophysiological relationship between cognitive deficit in BD and MS. The objective was to review the current literature regarding the possible pathophysiological explanation of the relationship between BD and MS and its effect on cognitive performance of patients with BD., Methods: A bibliographic search was carried out using MEDLINE, ClinicalKey, EMBASE, Literatura Latino-Americana y del Caribe en Ciencias de la Salud [Latin American and Caribbean Literature in Health Sciences] (LILACS), APA PsycNet, Scopus and Scielo databases, and the Pan-American Medical Electronic Library; using the following search terms: "bipolar disorder"[MeSH Terms] OR "bipolar disorder"[All Fields] OR "mood disorders"[All Fields] AND "cognitive deficit"[MeSH Terms] OR "cognitive deficit"[All Fields] OR "cognitive dysfunction"[All Fields] OR "cognitive impairment"[All Fields] OR "cognitive decline"[All Fields] AND "metabolic syndrome" [MeSH Terms] OR "metabolic abnormalities"[All Fields] OR "metabolic effects"[All Fields] OR "obesity" [All Fields] OR "abdominal obesity" [All Fields] OR "overweight" [All Fields] OR "diabetes" [All Fields] OR "hypertension" [All Fields] AND "antipsychotics" [MeSH Terms] OR "antipsychotics"[All Fields] AND "antidepressants" [MeSH Terms] OR "antidepressants"[All Fields] AND "mood stabilizers" [MeSH Terms] OR "mood stabilizers"[All Fields]. Filters: free full text, full text, from 2001 to 2022. A total of 80 articles in Spanish and English, of any type of design, were selected. Selection and reading were carried out by all the authors., Results and Conclusions: The various pathophysiological hypotheses proposed, inflammatory, endocrine, drug, environmental and social, suggest that a series of changes at the macro and microcellular level are correlated in patients with BD and MS with a negative effect on cognition of patients both globally and in specific domains, mainly executive function, memory, attention, and perceptual motor skills. Research processes should be continued to explore the various hypotheses that support the relationship between BD, MS and cognition., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Introduction: Addiction behaviors are primary contributors to mental health issues among adolescents, often utilized as coping mechanisms or emotional regulation tools. This study aimed to establish the content validity of the Penn Alcohol Craving Scale (PACS) for Colombian adolescents, recognized for its representation of the cognitive-emotional aspects of craving., Methodology: This quantitative research focused on instrument validation. Seven subject matter experts evaluated the scale in terms of pertinence, relevance, usefulness, sufficiency, clarity, and appearance. Data analysis was conducted using SPSS version 22, calculating internal consistency and the Content Validity Index. Qualitative feedback from experts was compiled in an Excel matrix, facilitating grammatical and semantic adjustments to the instrument., Results: Cronbach's Alpha values for each item and the scale exceeded 0.8. Content Validity Index scores exceeded 0.7 in four out of five evaluated criteria. These results supported retaining all scale items in the Colombian version., Conclusions: The content validation process yielded an instrument that satisfied expert opinion regarding conceptual constructs and explanatory power for the Colombian adolescent population.

Postpartum depression (PPD) affects 10-20% of women. Traditional treatments have raised concerns, but omega-3 fatty acids show potential as an alternative. This thematic review, sourced from databases like PubMed and Scopus between 1 February 2023 and 15 March 2023, seeks to delve into the various perspectives on omega-3 supplementation for PPD. The criteria included studies detailing depressive symptoms, social functioning, and neurobiological variables. The review includes research with women showing PPD symptoms, randomized clinical trials, and articles in Spanish, English, and French. Exclusions were studies lacking proper control comparisons and other interventions besides omega-3. Data extraction was performed independently. Two key studies provide contrasting findings on omega-3's impact on PPD symptoms. In the study comparing DHA supplementation to a placebo, significant differences were not found in the EPDS scale, but differences were observed in the BDI scale. In contrast, another study recorded a significant decrease in depression scores in all dose groups, with reductions of 51.5% in the EPDS scale and 48.8% in the HRSD scale. Other studies, encompassing both prenatal and postpartum periods, underscore the differentiation between prenatal depression and PPD. Despite shared diagnostic criteria, PPD presents unique symptoms like restlessness, emotional lability, and baby-related concerns. It is crucial to address biases and obtain specific results, recommending exclusive PPD-focused studies. This review emphasizes the need for continuous exploration of omega-3's relationship with PPD to enhance the life quality of pregnant women and their families.

Many medicines are used "off-label" in children outside the terms of the license. Feasible pediatric clinical trials are a challenge to design. Conect4children (c4c) is an Innovative Medicines Initiative project to set up a pan-European pediatric clinical trial network aiming to facilitate the development of new medicines for children. To optimize pediatric trial development by promoting innovative trial design, c4c set up a European multidisciplinary advice service, including the voice of young patients and families, tailored to industry and academia. A network of experts was established to provide multidisciplinary advice to trial sponsors. Experts were selected to join clinical and innovative methodology expert groups. A patient and public involvement (PPI) database, to include the expert opinion of patients and parents/carers was formed. A stepwise process was developed: (1) sponsors contact c4c, (2) scoping interview takes place, (3) ad hoc advice group formed, (5) advice meeting held, and (6) advice report provided. Feedback on the process was collected. Twenty-four clinical and innovative methodology expert groups (>400 experts) and a PPI database of 135 registrants were established. As of September 30, 2022, 36 advice requests were received, with 25 requests completed. Clinical and methodology experts and PPI representatives participated in several advice requests. Sponsors appreciated the advice quality and the multidisciplinary experts from different countries, including experts not known before. Experts and PPI participants were generally satisfied with the process. The c4c project has shown successful proof of concept for a service that presents a new framework to plan innovative and feasible pediatric trials., (© 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: The high prevalence of female breast cancer is a global health concern. Breast cancer and its treatments have been associated with impairments in general cognition, as well as structural and functional brain changes. Considering the social challenges that some of these patients face, it is important to understand the socio-emotional effects of breast cancer as well. Nevertheless, the impact of breast cancer on social cognition has remained underexplored. The objective of this study was to assess social cognition domains and other relevant cognitive and emotional variables (executive functions, anxiety, or depression) in females with breast cancer., Methods: The participants were 29 female patients diagnosed with breast cancer and 29 female healthy controls. We assessed emotion recognition, theory of mind, empathy, and moral emotions. We also included measures of general cognitive functioning, quality of life, anxiety, and depression. Linear multiple regressions were performed to assess whether the group (patients or controls), GAD-7 scores, emotional and social subscales of EORTC QLQ-C30, and IFS scores predicted the social cognition variables (EET, RMET, MSAT)., Results: Patients with breast cancer showed impairments in emotion recognition and in affective theory of mind. In addition, patients had lower scores in some executive functions. Only theory of mind between group differences remained significant after Bonferroni correction. Emotion recognition was associated with executive functioning, but anxiety levels were not a significant predictor of the changes in social cognition., Conclusions: Social cognition impairments, especially in theory of mind, may be present in breast cancer, which can be relevant to understanding the social challenges that these patients encounter. This could indicate the need for therapeutic interventions to preserve social cognition skills in patients with breast cancer., (© 2022. The Author(s).)

Background: Behavioral variant frontotemporal dementia (bvFTD) has been related to different genetic factors. Identifying multimodal phenotypic heterogeneity triggered by various genetic influences is critical for improving diagnosis, prognosis, and treatments. However, the specific impact of different genetic levels (mutations vs. risk variants vs. sporadic presentations) on clinical and neurocognitive phenotypes is not entirely understood, specially in patites from underrepresented regions such as Colombia., Methods: Here, in a multiple single cases study, we provide systematic comparisons regarding cognitive, neuropsychiatric, brain atrophy, and gene expression-atrophy overlap in a novel cohort of FTD patients (n = 42) from Colombia with different genetic levels, including patients with known genetic influences (G-FTD) such as those with genetic mutations (GR1) in particular genes (MAPT, TARDBP, and TREM2); patients with risk variants (GR2) in genes associated with FTD (tau Haplotypes H1 and H2 and APOE variants including ε2, ε3, ε4); and sporadic FTD patients (S-FTD (GR3))., Results: We found that patients from GR1 and GR2 exhibited earlier disease onset, pervasive cognitive impairments (cognitive screening, executive functioning, ToM), and increased brain atrophy (prefrontal areas, cingulated cortices, basal ganglia, and inferior temporal gyrus) than S-FTD patients (GR3). No differences in disease duration were observed across groups. Additionally, significant neuropsychiatric symptoms were observed in the GR1. The GR1 also presented more clinical and neurocognitive compromise than GR2 patients; these groups, however, did not display differences in disease onset or duration. APOE and tau patients showed more neuropsychiatric symptoms and primary atrophy in parietal and temporal cortices than GR1 patients. The gene-atrophy overlap analysis revealed atrophy in regions with specific genetic overexpression in all G-FTD patients. A differential family presentation did not explain the results., Conclusions: Our results support the existence of genetic levels affecting the clinical, neurocognitive, and, to a lesser extent, neuropsychiatric presentation of bvFTD in the present underrepresented sample. These results support tailored assessments characterization based on the parallels of genetic levels and neurocognitive profiles in bvFTD., (© 2022. The Author(s).)

T cell-based therapies have been widely explored for the treatment of cancer and chronic infection, but B cell-based therapies have remained largely unexplored. To study the effect of B cell therapy, we adoptively transferred virus-specific B cells into mice that were chronically infected with lymphocytic choriomeningitis virus (LCMV). Adoptive transfer of virus-specific B cells resulted in increase in antibody titers and reduction of viral loads. Importantly, the efficacy of B cell therapy was partly dependent on antibody effector functions, and was improved by co-transferring virus-specific CD4 T cells. These findings provide a proof-of-concept that adoptive B cell therapy can be effective for the treatment of chronic infections, but provision of virus-specific CD4 T cells may be critical for optimal virus neutralization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chung, Dangi, Palacio, Sanchez and Penaloza-MacMaster.)

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have shown efficacy against SARS-CoV-2, it is unknown if coronavirus vaccines can also protect against other coronaviruses that may infect humans in the future. Here, we show that coronavirus vaccines elicited cross-protective immune responses against heterologous coronaviruses. In particular, we show that a severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) vaccine developed in 2004 and known to protect against SARS-CoV-1 conferred robust heterologous protection against SARS-CoV-2 in mice. Similarly, prior coronavirus infections conferred heterologous protection against distinct coronaviruses. Cross-reactive immunity was also reported in patients with coronavirus disease 2019 (COVID-19) and in individuals who received SARS-CoV-2 vaccines, and transfer of plasma from these individuals into mice improved protection against coronavirus challenges. These findings provide the first demonstration to our knowledge that coronavirus vaccines (and prior coronavirus infections) can confer broad protection against heterologous coronaviruses and establish a rationale for universal coronavirus vaccines.

SARS-CoV-2 has caused a global pandemic that has infected more than 250 million people worldwide. Although several vaccine candidates have received emergency use authorization, there is still limited knowledge on how vaccine dosing affects immune responses. We performed mechanistic studies in mice to understand how the priming dose of an adenovirus-based SARS-CoV-2 vaccine affects long-term immunity to SARS-CoV-2. We first primed C57BL/6 mice with an adenovirus serotype 5 vaccine encoding the SARS-CoV-2 spike protein, similar to that used in the CanSino and Sputnik V vaccines. The vaccine prime was administered at either a standard dose or 1000-fold lower dose, followed by a boost with the standard dose 4 weeks later. Initially, the low dose prime induced lower immune responses relative to the standard dose prime. However, the low dose prime elicited immune responses that were qualitatively superior and, upon boosting, exhibited substantially more potent recall and functional capacity. We also report similar effects with a simian immunodeficiency virus (SIV) vaccine. These findings show an unexpected advantage of fractionating vaccine prime doses, warranting a reevaluation of vaccine trial protocols for SARS-CoV-2 and other pathogens.

SARS-CoV-2 infection causes respiratory insufficiency and neurological manifestations, including loss of smell and psychiatric disorders, and can be fatal. Most vaccines are based on the spike antigen alone, and although they have shown efficacy at preventing severe disease and death, they do not always confer sterilizing immunity. Here, we interrogate whether SARS-CoV-2 vaccines could be improved by incorporating nucleocapsid as an antigen. We show that, after 72 h of challenge, a spike-based vaccine confers acute protection in the lung, but not in the brain. However, combining a spike-based vaccine with a nucleocapsid-based vaccine confers acute protection in both the lung and brain. These findings suggest that nucleocapsid-specific immunity can improve the distal control of SARS-CoV-2, warranting the inclusion of nucleocapsid in next-generation COVID-19 vaccines., Competing Interests: Declaration of interests P.P.M. reports being Task Force Advisor to the Illinois Department of Public Health (IDPH) on SARS-CoV-2 vaccines. P.P.M. is also a member/advisor of the COVID-19 Vaccine Regulatory Science Consortium (CoVAXCEN) at Northwestern University’s Institute for Global Health., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Type I interferons (IFN-I) are a major antiviral defense and are critical for the activation of the adaptive immune system. However, early viral clearance by IFN-I could limit antigen availability, which could in turn impinge upon the priming of the adaptive immune system. In this study, we hypothesized that transient IFN-I blockade could increase antigen presentation after acute viral infection. To test this hypothesis, we infected mice with viruses coadministered with a single dose of IFN-I receptor-blocking antibody to induce a short-term blockade of the IFN-I pathway. This resulted in a transient "spike" in antigen levels, followed by rapid antigen clearance. Interestingly, short-term IFN-I blockade after coronavirus, flavivirus, rhabdovirus, or arenavirus infection induced a long-lasting enhancement of immunological memory that conferred improved protection upon subsequent reinfections. Short-term IFN-I blockade also improved the efficacy of viral vaccines. These findings demonstrate a novel mechanism by which IFN-I regulate immunological memory and provide insights for rational vaccine design., Competing Interests: Disclosures: N. Palacio and P. Penaloza-MacMaster reported that a provisional patent application was submitted (transient interferon blockade to enhance immune responses to antigens and improve vaccines). No other disclosures were reported., (© 2020 Palacio et al.)

In this invited article, we explain technical aspects of the lymphocytic choriomeningitis virus (LCMV) system, providing an update of a prior contribution by Matthias von Herrath and J. Lindsay Whitton. We provide an explanation of the LCMV infection models, highlighting the importance of selecting an appropriate route and viral strain. We also describe how to quantify virus-specific immune responses, followed by an explanation of useful transgenic systems. Specifically, our article will focus on the following protocols. © 2020 Wiley Periodicals LLC. Basic Protocol 1: LCMV infection routes in mice Support Protocol 1: Preparation of LCMV stocks ASSAYS TO MEASURE LCMV TITERS Support Protocol 2: Plaque assay Support Protocol 3: Immunofluorescence focus assay (IFA) to measure LCMV titer MEASUREMENT OF T CELL AND B CELL RESPONSES TO LCMV INFECTION Basic Protocol 2: Triple tetramer staining for detection of LCMV-specific CD8 T cells Basic Protocol 3: Intracellular cytokine staining (ICS) for detection of LCMV-specific T cells Basic Protocol 4: Enumeration of direct ex vivo LCMV-specific antibody-secreting cells (ASC) Basic Protocol 5: Limiting dilution assay (LDA) for detection of LCMV-specific memory B cells Basic Protocol 6: ELISA for quantification of LCMV-specific IgG antibody Support Protocol 4: Preparation of splenic lymphocytes Support Protocol 5: Making BHK21-LCMV lysate Basic Protocol 7: Challenge models TRANSGENIC MODELS Basic Protocol 8: Transfer of P14 cells to interrogate the role of IFN-I on CD8 T cell responses Basic Protocol 9: Comparing the expansion of naïve versus memory CD4 T cells following chronic viral challenge., (© 2020 Wiley Periodicals LLC.)

Objective: To analyze the psychological, social and family dimensions of a health professional quarantined by COVID-19., Method: Case report. A matrix was used as a daily log to collect information from the three dimensions analyzed. The anonymity of the person was respected at all times., Results: A case study is presented with the main milestones in the daily life of a health professional during the 14 days of quarantine. In the psychological dimension, feelings of fear and uncertainty in the face of risk are highlighted, in the social dimension the importance of the accompaniment of family and friends who strengthened the adaptability to the process stands out, and in the family dimension the relevance of affective bonds and permanent communication., Conclusion: The aspects developed in the different dimensions should be considered by those who participate in the management and follow-up of cases in primary care, as they are the possibility of strengthening the neuronal and hormonal mechanism through family and social support. Being a health professional and having knowledge on the subject can generate a greater effect of involuntary isolation related to the risk of COVID-19. This is not only clinical, but also psychological, social and family. In this sense those who manage the cases should consider the integrality in health conditions.

The study of functional connectivity and declarative memory has lately been focused on finding biomarkers of neuropsychological diseases. However, little is known about its patterns in healthy brains. Thus, in this systematic review we analyze and integrate the findings of 81 publications regarding functional connectivity (measured by fMRI during both task and resting-state) and semantic and episodic memory in healthy adults. Moreover, we discriminate and analyze the main areas and links found in specific memory phases (encoding, storage or retrieval) based on several criteria, such as time length, depth of processing, rewarding value of the information, vividness and amount or kind of details retrieved. There is a certain degree of overlap between the networks of episodic and semantic memory and between the encoding and retrieval stages. Although several differences are pointed out during the article, this calls to attention the need for further empirical studies that actively compare both types of memory, particularly using other baseline conditions apart from the traditional resting state. Indeed, the active involvement of the default mode network in both declarative memory and resting condition suggests the possibility that during rest there is an on-going memory processing. We find support for the 'attention to memory' hypothesis, the memory differentiation model and the appropriate transfer hypothesis, but some evidence is inconsistent with the traditional hub-and-spoke model.

CD8 T cells are necessary for the elimination of intracellular pathogens, but during chronic viral infections, CD8 T cells become exhausted and unable to control the persistent infection. Programmed cell death-1 (PD-1) blockade therapies have been shown to improve CD8 T cell responses during chronic viral infections. These therapies have been licensed to treat cancers in humans, but they have not yet been licensed to treat chronic viral infections because limited benefit is seen in pre-clinical animal models of chronic infection. In the present study, we investigated whether TLR4 triggering could improve PD-1 therapy during a chronic viral infection. Using the model of chronic lymphocytic choriomeningitis virus (LCMV) infection in mice, we show that TLR4 triggering with sublethal doses of lipopolysaccharide (LPS) followed by PD-1 blockade results in superior improvement in circulating virus-specific CD8 T cell responses, relative to PD-1 blockade alone. Moreover, we show that the synergy between LPS and PD-1 blockade is dependent on B7 costimulation and mediated by a dendritic cell (DC) intrinsic mechanism. Systemic LPS administration may have safety concerns, motivating us to devise a safer regimen. We show that ex vivo activation of DCs with LPS, followed by adoptive DC transfer, results in a similar potentiation of PD-1 therapy without inducing wasting disease. In summary, our data demonstrate a previously unidentified role for LPS/TLR4 signaling in modulating the host response to PD-1 therapy. These findings may be important for developing novel checkpoint therapies against chronic viral infection., Competing Interests: The authors have declared that no competing interests exist.

Introduction: One of the most important risk factors for hepatocellular carcinoma (HCC) is alcohol consumption: Studies in different populations suggest that the risk of liver disease could be associated with genetic variants of the enzymes involved in alcohol metabolism, such as alcohol dehydrogenase (ADH) and cytochrome P450 CYP2E1. Objective: To identify and characterize the allelic variants of ADH1B, ADH1C and CYP2E1 genes in Colombian patients with cirrhosis and/or HCC. Materials and methods: We included samples from patients attending the hepatology unit between 2005-2007 and 2014-2016 of a hospital in Medellin. Samples were genotyped using PCR-RFLP. We compared the results with two control groups and the 1000 Genomes Project database. Results: We collected 97 samples from patients with a diagnosis of cirrhosis and/or HCC. The two main risk factors were chronic alcohol consumption (18.6%) and cholangiopathies (17.5%). The most frequent genotypes in the study population were ADH1B*1/1 (82%), ADH1C*1/1 (59%), and CYP2E1*C/C (84%). Conclusions: This first study of polymorphisms in Colombian patients diagnosed with cirrhosis and/or HCC showed genotypes ADH1B*1/1, ADH1C*1/1 and CYP2E1*C/C as the most frequent. We found no significant differences in the genotype frequency between cases and controls. Further studies are necessary to explore the association between polymorphisms and the risk of end-stage liver disease from alcohol consumption.

Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-lowering therapy. However, all lipoproteins containing apolipoprotein B (apo B) appear to be atherogenic. Preferred targets of therapy therefore may include either the cholesterol in all apo B-containing lipoproteins (non-high-density lipoprotein cholesterol [non-HDL-C]) or total apo B itself. Apo B can be measured by three methods: chemically, by nuclear magnetic resonance (NMR), and by immunoassay. This study compares the first two methods as a function of the number of metabolic risk factors in patients with metabolic syndrome. Plasma lipid, lipoprotein cholesterol, and apo B levels were measured in 274 adults with varying numbers of metabolic syndrome components. Low-density lipoprotein (LDL) particle sizes were measured by gel electrophoresis and by NMR. Total apo B was estimated chemically and by conversion of NMR lipoprotein particle number, assuming one apo B molecule per lipoprotein particle. As the number of metabolic syndrome components increased, apo B rose by both chemical and NMR methods, but by chemical methods, increases were in the triglyceride-rich fraction, whereas by NMR, they were in LDL. The correlation between total apo B measured by the two methods was only moderate (r = .73). Further, non-HDL-C was more highly correlated with total apo B measured chemically than either LDL-C or total apo B by NMR. Non-HDL-C correlates highly with total apo B in patients with metabolic syndrome and had advantages as a target of therapy over LDL-C or NMR apo B.

Background: Plasma lipid abnormalities commonly persist in patients with diabetic dyslipidemia in spite of statin monotherapy., Objective: The aim of this study was to determine whether fenofibrate plus low-dose nicotinic acid adequately improves the lipoprotein profile in patients with diabetic dyslipidemia who are being treated with a statin., Methods: In this open-label, crossover study, patients with type 2 diabetes mellitus who were receiving statin treatment were enrolled at the Lipid Clinic of the Veterans Affairs Medical Center, Dallas, Texas, and administered simvastatin 20 mg/d for 8 weeks. At the end of the 8-week period, fenofibrate 160 mg/d was added for 8 weeks, followed by the addition of extended-release nicotinic acid 1 g/d for an additional 8 weeks. The first subject was recruited on September 25, 2003, and the last subject was recruited on September 28, 2004. Liver function tests, creatine phosphokinase activity, and blood glucose levels were assessed every 4 weeks to assess tolerability. Levels of fasting plasma lipids and lipoprotein cholesterol were measured every 8 weeks on 3 consecutive days in each patient; C-reactive protein, lipoprotein pattern, and glycosylated hemoglobin levels were assessed once every 8 weeks. Plasma levels of total cholesterol, triglycerides, very-low-density lipoprotein plus intermediate-density lipoprotein cholesterol (VLDL+IDL-C), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B were also measured., Results: Twenty-six patients were enrolled in the study and 20 patients (18 men, 2 women; mean [SD] age, 58.8 [6.5] years) completed it. The mean plasma triglyceride level was significantly decreased (-29.2%; P= 0.004) and the mean HDL-C level was significantly increased (+13.5%; P < 0.001) with 3-drug treatment (simvastatin + fenofibrate + extended-release nicotinic acid) compared with simvastatin monotherapy. Significant reductions in plasma levels of VLDL+IDL-C (-35.7%; P = 0.001), VLDL+IDL-apolipoprotein B (-30%; P = 0.005), non-HDL-C (-12.9%; P = 0.001), and total-apolipoprotein B (-17.9%; P < 0.001) were seen with the 3-drug treatment compared with simvastatin alone. Compared with simvastatin monotherapy, simvastatin + fenofibrate-treated (2-drug treatment) patients had significantly lower plasma levels of triglycerides (-24.9%; P = 0.014) and significantly higher levels of HDL-C (+5.4%; P = 0.008). Significant reductions were also seen in levels of VLDL+IDL-C (-28.6%; P = 0.004), VLDL+IDL-apolipoprotein B (-26.7%; P < 0.001), non-HDL-C (-9.1 %; P= 0.004), and total-apolipoprotein B (-12.3%; P < 0.001) in the 2-drug treatment group compared with the simvastatin monotherapy group. The administration of 3-drug treatment was associated with improved responses in all lipoprotein fractions, although only the increase in HDL-C level was statistically significant (+7.7%; P = 0.008) compared with 2-drug treatment., Conclusions: Treatment with the 3-drug regimen was associated with a significant reduction in triglyceride levels compared with simvastatin monotherapy. However, there was not a significant incremental reduction in triglyceride levels when nicotinic acid was added to the 2-drug treatment, suggesting that the triglyceride-lowering effect of fenofibrate + nicotinic acid is not cumulative. To obtain clinically meaningful responses, particularly for the treatment of elevated HDL-C, higher doses of nicotinic acid might be required.