Medical education and the healthcare system--why does the curriculum need to be reformed?

Medical education has been the subject of ongoing debate since the early 1900s. The core of the discussion is about the importance of scientific knowledge on biological understanding at the expense of its social and humanistic characteristics. Unfortunately, reforms to the medical curriculum are still based on a biological vision of the health-illness process. In order to respond to the current needs of society, which is education's main objective, the learning processes of physicians and their instruction must change once again. The priority is the concept of the health-illness process that is primarily social and cultural, into which the biological and psychological aspects are inserted. A new curriculum has been developed that addresses a comprehensive instruction of the biological, psychological, social, and cultural (historical) aspects of medicine, with opportunities for students to acquire leadership, teamwork, and communication skills in order to introduce improvements into the healthcare systems where they work.

New Hybrid Scaffolds Based on 5-FU/Curcumin: Synthesis, Cytotoxic, Antiproliferative and Pro-Apoptotic Effect.

A series of 5-FU-Curcumin hybrids were synthesized, and their structures were elucidated by spectroscopic analysis. The synthesized hybrid compounds were evaluated in different colorectal cancer cell lines (SW480 and SW620) and in non-malignant cells (HaCaT and CHO-K1), to determine their chemopreventive potential. Hybrids 6a and 6d presented the best IC50 value against the SW480 cell line with results of 17.37 ± 1.16 µM and 2.43 ± 0.33 µM, respectively. Similarly, compounds 6d and 6e presented IC50 results of 7.51 ± 1.47 µM and 14.52 ± 1.31 µM, respectively, against the SW620 cell line. These compounds were more cytotoxic and selective than curcumin alone, the reference drug 5-fluorouracil (5-FU), and the equimolar mixture of curcumin and 5-FU. In addition, hybrids 6a and 6d (in SW480) and compounds 6d and 6e (in SW620) induced cell cycle arrest in S-phase, and, compounds 6d and 6e caused a significant increase in the sub-G0/G1 phase population in both cell lines. Hybrid 6e was also observed to induce apoptosis of SW620 cells with a respective increase in executioner caspases 3 and 7. Taken together, these results suggest that the hybrids could actively act on a colorectal cancer model, making them a privileged scaffold that could be used in future research.

[Psychological Impact of COVID-19 on Health Workers During the Second Year of the Pandemic in Latin America: Cross-Sectional Survey Study]. / Impacto psicológico del COVID-19 en los trabajadores sanitarios durante el segundo año de pandemia en Latinoamérica: estudio de encuesta transversal.

Introduction: The coronavirus pandemic continues to affect the mental health of healthcare personnel in Latin America (LA). Objective: To estimate the prevalence of psychological disturbances and associated risk factors for mental health in healthcare personnel in LA during the second year of the COVID-19 pandemic. Method: This multicenter cross-sectional study included a total sample of 5437 healthcare professionals from Argentina, Bolivia, Chile, Colombia, Ecuador, and Peru. The PHQ-9, GAD-7, and a brief demographic questionnaire were used. The prevalence of anxiety and depression was estimated based on the cut-off points of the instruments. Two multivariate logistic regressions were performed. Results: A population burden of anxiety (40.1%) and depression (62.2%) was found in healthcare personnel in LA. Among professionals in Argentina (OR = 1.374; P<.001), those working in state hospitals (OR = 1.536; P<.003), frontline healthcare workers for COVID patients (OR = 1.848; P<.001), general practitioners (OR = 1.335; P<.001), and specialists (OR = 1.298; P<.001), a higher risk of experiencing mental disorders was observed. Among women, younger personnel, and administrative staff, a higher probability of experiencing anxiety and depression was identified. Conclusions: The burden of mental disorders on healthcare personnel in Latin America is alarming. Psychological support services are necessary, aimed at providing measures for professionals to develop healthy coping mechanisms that mitigate the impact of the pandemic on their well-being and facilitate post-crisis adjustment.

IL-4, IL-10, CCL2 and TGF-ß as potential biomarkers for severity in Plasmodium vivax malaria.

Cytokines and chemokines are immune response molecules that display diverse functions, such as inflammation and immune regulation. In Plasmodium vivax infections, the uncontrolled production of these molecules is thought to contribute to pathogenesis and has been proposed as a possible predictor for disease complications. The objective of this study was to evaluate the cytokine profile of P. vivax malaria patients with different clinical outcomes to identify possible immune biomarkers for severe P. vivax malaria. The study included patients with non-severe (n = 56), or severe (n = 50) P. vivax malaria and healthy controls (n = 50). Patient plasma concentrations of IL-4, IL-2, CXCL10, IL-1ß, TNF-α, CCL2, IL-17A, IL-6, IL-10, IFN-γ, IL-12p70, CXCL8 and active TGF-ß1 were determined through flow cytometry. The levels of several cytokines and chemokines, CXCL10, IL-10, IL-6, IL-4, CCL2 and IFN-γ were found to be significantly higher in severe, compared to non-severe P. vivax malaria patients. Severe thrombocytopenia was positively correlated with IL-4, CXCL10, IL-6, IL-10 and IFN-γ levels, renal dysfunction was related to an increase in IL-2, IL-1ß, IL-17A and IL-8, and hepatic impairment with CXCL10, MCP-1, IL-6 and IFN-γ. A Lasso regression model suggests that IL-4, IL-10, CCL2 and TGF-ß might be developed as biomarkers for severity in P. vivax malaria. Severe P. vivax malaria patients present specific cytokine and chemokine profiles that are different from non-severe patients and that could potentially be developed as biomarkers for disease severity.

Resveratrol/Hydrazone Hybrids: Synthesis and Chemopreventive Activity against Colorectal Cancer Cells.

A series of resveratrol/hydrazone hybrids were obtained and elucidated by spectroscopic analysis. All compounds were evaluated against colorectal cancer cells (SW480 and Sw620) and nonmalignant cell lines (HaCaT and CHO-K1) to establish the selectivity index. Among the hybrids evaluated, compounds 6e and 7 displayed the highest cytotoxic activity with IC50 values of = 6.5 ± 1.9 µM and 19.0 ± 1.4 µM, respectively, on SW480 cells. In addition, hybrid 7 also exhibited activity on SW620 cells with an IC50 value of 38.41 ± 3.3 µM. Both compounds were even more toxic against these malignant cells in comparison to the nonmalignant ones, as evidenced by higher selectivity indices 48 h after treatment. These compounds displayed better activity and selectivity than parental compounds (PIH and Resveratrol) and the reference drug (5-FU). In addition, it was observed that both compounds caused antiproliferative activity probably exerted by cell cycle arrest at the G2/M or G0/G1 phases, with the formation of cells in the subG0/G1 phase. Furthermore, it was noticed that compound 7 induced mitochondrial depolarization in SW480 cells and positive staining for propidium iodide in both cancer cell lines, suggesting cell membrane damage involving either apoptosis or other processes of death.

Synthesis and Chemopreventive Potential of 5-FU/Genistein Hybrids on Colorectal Cancer Cells.

A series of 5-FU-Genistein hybrids were synthesized and their structures were elucidated by spectroscopic analysis. The chemopreventive potential of these compounds was evaluated in human colon adenocarcinoma cells (SW480 and SW620) and non-malignant cell lines (HaCaT and CHO-K1). Hybrid 4a displayed cytotoxicity against SW480 and SW620 cells with IC50 values of 62.73 ± 7.26 µM and 50.58 ± 1.33 µM, respectively; compound 4g induced cytotoxicity in SW620 cells with an IC50 value of 36.84 ± 0.71 µM. These compounds were even more selective than genistein alone, the reference drug (5-FU) and the equimolar mixture of genistein plus 5-FU. In addition, hybrids 4a and 4g induced time- and concentration-dependent antiproliferative activity and cell cycle arrest at the S-phase and G2/M. It was also observed that hybrid 4a induced apoptosis in SW620 cells probably triggered by the extrinsic pathway in response to the activation of p53, as evidenced by the increase in the levels of caspases 3/8 and the tumor suppressor protein (Tp53). Molecular docking studies suggest that the most active compound 4a would bind efficiently to proapoptotic human caspases 3/8 and human Tp53, which in turn could provide valuable information on the biochemical mechanism for the in vitro cytotoxic response of this compound in SW620 colon carcinoma cell lines. On the other hand, molecular dynamics (MD) studies provided strong evidence of the conformational stability of the complex between caspase-3 and hybrid 4a obtained throughout 100 ns all-atom MD simulation. Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analyses of the complex with caspase-3 showed that the interaction between the ligand and the target protein is stable. Altogether, the results suggest that the active hybrids, mainly compound 4a, might act by modulating caspase-3 activity in a colorectal cancer model, making it a privileged scaffold that could be used in future investigations.

[Prevalence and factors associated with subjective cognitive complaints in Latin American health workers during the COVID-19 pandemic]. / Prevalencia y factores asociados con las quejas cognitivas subjetivas del personal sanitario latinoamericano durante la pandemia de COVID-19.

Background and objectives: An increase in emotional disturbances and complaints about cognitive performance has been observed in Latin American healthcare workers during the SARS-CoV-2 pandemic, which can affect attention capacity and increase the levels of stress and burnout of these professionals. The objective was to analyse subjective cognitive complaints (SCC) and associated factors in health personnel during the COVID-19 pandemic in five Latin American countries.Methods: Multicentre cross-sectional study, which included 3,738 professionals from Colombia, Chile, Argentina, Ecuador, Bolivia, and Peru. The Generalized Anxiety Disorder Scale (GAD-7) and the Patient Health Questionnaire (PHQ-9) was used to assess depression, and the Mini-Z to assess Burnout. For the SCC, an item on cognitive concerns in attention and memory was used.Results: The prevalence of cognitive complaints was 69.2%. The factors associated with a higher risk of SCC were the scores in the GAD-7, PHQ and Mini-Z, in addition to being part of the Ecuadorian health personnel.Conclusions: There is a high prevalence of SCC in health personnel, which is modulated by emotional states and stress.

Presentation of Bilateral Facial Paralysis in Melkersson-Rosenthal Syndrome.

Introduction. Melkersson-Rosenthal syndrome (MRS) is a neuromucocutaneous disorder characterized by the following classic symptom triad: peripheral facial paralysis, orofacial edema, and scrotal or fissured tongue. It is rare, and since most of the patients are oligo- or monosymptomatic, it makes it difficult to diagnose. Clinical Case. We present a 26-year-old male patient with a history of sickle cell trait, untreated snoring, and left peripheral facial paralysis when he was 11 years old. This was an overall 20-day clinical profile that started with left peripheral facial paralysis, which was accompanied by moderate-intensity occipital pulsatile headaches. Additionally, the patient experienced paresthesias in the tongue and feelings of labial edema. After one week, he manifested peripheral facial paralysis on the right side. Physical examination revealed bilateral peripheral facial paralysis, mild labial edema, and a scrotal or fissured tongue. The patient received corticosteroids, which resulted in improvement of the edema and facial paralysis. Discussion. MRS is a rare disorder that predominantly affects women, typically starting in their 20s or 30s. The etiology is unknown. However, a multifactorial origin that involves environmental factors and a genetic predisposition has been proposed, which causes a dysfunction of the local immune system and autonomic nervous system (ANS) and an appearance of granulomatous inflammation in the lips and tongue. Facial paralysis usually appears later on; however, it can occur from its clinical debut. There are no curative treatments. Therapy is focused on modulating the patient's immune response, and relapses are frequent.

Educational Strategies to Develop and Implement a Comprehensive Health Care Model Focused on Primary Care in Colombia.

The traditional, subject-based medical curriculum in Colombia has been mainly focused on the biomedical model proposed by Flexner in 1910. This means learning outcomes or competences are framed on curative care and the specialization of physicians. Students are mainly trained to work in highly complex hospitals in urban centers and encouraged to enroll (as soon as possible) in residencies. This curriculum lacks pertinence to implement the new Colombian Primary Health Care Model as the focus is a shift toward the promotion of health and prevention of illness. Recommendations to provide light on how to implement a change for ensuring pertinence of medical education in this context are discussed.

Harris's hawks (Parabuteo unicinctus) hematological parameters in different tropical locations.

This work described and compared the hematological findings of 25 clinically healthy Harris's hawks (Parabuteo unicinctus) in captivity at two different tropical locations: 16 samples from Aguascalientes, which altitude is 1878 mean sea level, and nine samples from Amecameca which altitude is 2650 mean sea level. Blood samples were collected from the brachial vein of each raptor under physical restraint. Significant differences between the two locations were found in some parameters including total, erythrocytes, heterophils, basophils, lymphocytes, and heterophil/lymphocyte ratio. When the results were compared to the reference values, the population of Amecameca showed decreased values of hematocrit (32.21 ± 13.72%), hemoglobin (107.40 ± 45.60 g L-1) and erythrocytes (1.98 ± 0.63 ×1012 per µL). This work contributed to the knowledge of variations in blood parameters of clinically healthy captive Harris`s hawks at different tropical locations and sex. The information will enable clinicians to provide appropriate veterinary diagnostics and care to ensure the health and welfare of raptors kept in captivity.

Targeting Neuroplasticity, Cardiovascular, and Cognitive-Associated Genomic Variants in Familial Alzheimer's Disease.

The identification of novel genetic variants contributing to the widespread in the age of onset (AOO) of Alzheimer's disease (AD) could aid in the prognosis and/or development of new therapeutic strategies focused on early interventions. We recruited 78 individuals with AD from the Paisa genetic isolate in Antioquia, Colombia. These individuals belong to the world largest multigenerational and extended pedigree segregating AD as a consequence of a dominant fully penetrant mutation in the PSEN1 gene and exhibit an AOO ranging from the early 1930s to the late 1970s. To shed light on the genetic underpinning that could explain the large spread of the age of onset (AOO) of AD, 64 single nucleotide polymorphisms (SNP) associated with neuroanatomical, cardiovascular, and cognitive measures in AD were genotyped. Standard quality control and filtering procedures were applied, and single- and multi-locus linear mixed-effects models were used to identify AOO-associated SNPs. A full two-locus interaction model was fitted to define how identified SNPs interact to modulate AOO. We identified two key epistatic interactions between the APOE*E2 allele and SNPs ASTN2-rs7852878 and SNTG1-rs16914781 that delay AOO by up to ~ 8 years (95% CI 3.2-12.7, P = 1.83 × 10-3) and ~ 7.6 years (95% CI 3.3-11.8, P = 8.69 × 10-4), respectively, and validated our previous finding indicating that APOE*E2 delays AOO of AD in PSEN1 E280 mutation carriers. This new evidence involving APOE*E2 as an AOO delayer could be used for developing precision medicine approaches and predictive genomics models to potentially determine AOO in individuals genetically predisposed to AD.

The influence of different curriculum designs on students' dropout rate: a case study.

The relationship between students' withdrawal and educational variables has generated a considerable number of publications. As the explosion of information in sciences and integration theories led to creating different curriculum designs, it has been assumed that differences among designs explain academic success and, therefore, students' retention. However, little attention has been given to examine explicitly how diverse designs influence dropout rates in practice, which questions if decisions to reform curricula are sufficiently informed. This article describes our curriculum reform, which exposes our former and current curriculum designs as having had dissimilar dropout percentages. Furthermore, we aimed to explore the influence of different curriculum designs on students' dropout rates. The conclusion is that dropout variations may be explained not only because of the curriculum design itself, but also because of the power relationship changes between teachers and students that brought out the design change. Consequently, more research is needed to fully understand the political implications of different curriculum designs and their influence on dropout rates.

Integrated Medical Curriculum: Advantages and Disadvantages.

Most curricula for medical education have been integrated horizontally and vertically--vertically between basic and clinical sciences. The Flexnerian curriculum has disappeared to permit integration between basic sciences and clinical sciences, which are taught throughout the curriculum. We have proposed a different form of integration where the horizontal axis represents the defined learning outcomes and the vertical axis represents the teaching of the sciences throughout the courses. We believe that a mere integration of basic and clinical sciences is not enough because it is necessary to emphasize the importance of humanism as well as health population sciences in medicine. It is necessary to integrate basic and clinical sciences, humanism, and health population in the vertical axis, not only in the early years but also throughout the curriculum, presupposing the use of active teaching methods based on problems or cases in small groups.

Aotus lemurinus griseimembra monkeys: a suitable model for Plasmodium vivax sporozoite infection.

This study describes a successful Plasmodium vivax sporozoite infection in Aotus lemurinus griseimembra. Twenty-eight naive or previously infected monkeys, either splenectomized or spleen intact, were inoculated intravenously or subcutaneously with Plasmodium vivax sporozoites of the Salvador I strain or with two wild isolates (VCC-4 and VCC-5; Vivax-Cali-Colombia). The monkeys were successfully infected regardless of the parasite strain, spleen presence, or inoculation route and showed prepatent periods that ranged from 16 to 89 days. Only one monkey inoculated intravenously failed to develop parasitemia. Since immune protection against malaria pre-erythrocytic forms is mediated by both helper and cytolytic T cells that may home in the spleen and P. vivax cultures are not yet available; the use of spleen-intact A. lemurinus griseimembra, susceptible to both adapted and non-adapted strains of P. vivax sporozoites, is a valuable model for evaluation of pre-erythrocytic vaccine candidates.

Antigenicity, immunogenicity, and protective efficacy of Plasmodium vivax MSP1 PV200l: a potential malaria vaccine subunit.

The merozoite surface protein 1 (MSP-1) is expressed in all Plasmodium species and is considered a major malaria vaccine candidate. We found that MSP-1 from Plasmodium vivax (PvMSP-1) contains a region of significant sequence homology with the 190L subunit vaccine derived from the P. falciparum MSP-1. The fragment, termed Pv200L, was expressed as a recombinant protein in Escherichia coli (rPv200L) and used to asses its immunologic relevance as a vaccine target. A cross-sectional, seroepidemiologic study conducted in Buenaventura, Colombia showed that 52.2% (95% confidence interval [CI] = 39.8-64.3) of individuals previously exposed to P. vivax and 72.8% (95% CI = 61.8-82.1) of P. vivax-infected patients had IgG antibodies to rPv200L. Immunization of BALB/c mice and Aotus monkeys induced IgG antibodies (titer > 10(6)) that cross-reacted with P. vivax parasites. Immunized monkeys displayed partial protection against a challenge with P. vivax blood stages. Our results suggest that Pv200L is a new malaria vaccine subunit and deserves further testing.

Use of long synthetic peptides to study the antigenicity and immunogenicity of the Plasmodium vivax circumsporozoite protein.

Three long synthetic peptides corresponding to amino (N), repeat (R) and carboxyl (C) regions of the Plasmodium vivax circumsporozoite (CS) protein were synthesised and used to assess their potential as vaccine candidates. Antigenicity studies were carried out using human blood samples from residents of a malaria-endemic area of Colombia, and immunogenicity was tested in Aotus monkeys. The N and C peptides spanned the total native amino and carboxyl flanking regions, whereas the R peptide corresponded to a construct based on the first central nona-peptide repeated in tandem three times and colinearly linked to a universal T-cell epitope (ptt-30) derived from tetanus toxin. All three peptides had been shown previously to contain several B-, T-helper (Th) and Cytotoxic T Lymphocytes (CTL) epitopes. Sixty-one percent of the human sera reacted with the R region, whereas 35 and 39% of the samples had antibodies against the N and C peptides, respectively. Human Peripheral Blood Mononuclear Cells (PBMC) showed higher levels of IFN-gamma than IL-4 when stimulated with peptides containing Th epitopes. Aotus monkeys immunised with the peptides formulated in either Montanide ISA720 or Freund's adjuvants produced strong antibody responses that recognised the peptide immunogens and the native circumsporozoite protein on sporozoites. Additionally, high IFN-gamma production was induced when Aotus lymphocytes were stimulated in vitro with each of the three peptides. We observed boosting of antibody responses and IFN-gamma production by exposure to live sporozoites. These results confirm the high antigenicity and immunogenicity of such synthetic polypeptides and underline their vaccine potential.

Reproducible infection of intact Aotus lemurinus griseimembra monkeys by Plasmodium falciparum sporozoite inoculation.

Aotus lemurinus griseimembra is considered one of the best nonhuman primate species for malarial studies because of its susceptibility to infection by Plasmodium falciparum asexual blood stages. However, reproducible transmission of infective P. falciparum sporozoites by mosquito inoculation has been difficult to achieve even in splenectomized monkeys. Characterization of an Aotus-P. falciparum cyclical transmission model has become a top priority as a result of the significant progress toward the development of preerythrocytic malaria vaccines. Herein, we describe a reproducible model developed using intact A. lemurinus griseimembra monkeys intravenously inoculated with sporozoites from a monkey-adapted P. falciparum (Santa Lucia) strain and a wild Falciparum-Cali-Colombia-4 (FCC-4) strain. Sporozoites were obtained by salivary gland dissection of laboratory-reared Anopheles albimanus mosquitoes. Parasitemia was monitored by thick-smear microscopy, parasite lactate dehydrogenase (pLDH) determination, and mosquito xenodiagnosis. The last method proved to be the most sensitive method for monitoring parasitemias. Infection with the Santa Lucia strain showed a mean prepatent period of 16 days (range 6-21 days), whereas infection with the wild FCC-4 strain resulted in a 24-day prepatent period. Mean peak parasite density was approximately 900 parasites/microliter for both parasite strains. The prepatent period, the peak of parasitemia, and the duration of patency were independent of the size of the sporozoite inoculum and the presence of spleen in the host. This model is being successfully used to test the protective efficacy of P. falciparum preerythrocytic vaccine candidates.

Integración curricular mecanicista versus sistémica / Curricular integration in medical education

Introducción: la integración curricular ha sido un factor fundamental para el desarrollo de los currículos médicos modernos; sin embargo, en sus modelos más conocidos, que incluyen la integración horizontal y vertical, se continúan entendiéndose el aprendizaje de la medicina en torno a temas, tal como se hace en los currículos tradicionales. Esta manera de concebir el aprendizaje no permite analizar de manera metodológica el diseño de currículos integrados/integradores que involucran otras formas de aprender. Objetivo: suscitar una reflexión teórica y metodológica sobre la integración curricular en la educación médica con la finalidad de orientar el diseño y la evaluación de los currículos integrados/integradores y polemizar sobre qué tan innovadoras son las integraciones verticales y horizontales. Desarrollo: los currículos integrados horizontal y verticalmente son similares a los currículos tradicionales fragmentados en su concepción lineal del diseño, mientras que en la integración curricular sistémica, cuyos ejemplos pueden visualizarse en los currículos diseñados mediante el aprendizaje basado en problemas, se aborda el diseño curricular de manera circular mediante la conexión de cuestiones que se retroalimentan las unas a las otras, por tanto, las actividades de aprendizaje podrían diseñarse y evaluarse de forma simultánea. Conclusiones: al pensar en la integración curricular como una estrategia de innovación educativa implica debatir qué se entiende por currículos integrados/integradores, cómo se analizando la práctica de nuestros currículos médicos, con qué marcos teóricos estamos realizando ese análisis y qué implicaciones tiene esto en el diseño y la evaluación de los currículos(AU)

Introduction: Curricular integration has been a fundamental factor in the development of modern medical curricula; however, in its more well-known models, including horizontal and vertical integrations, the learning of medicine around subjects, as it is done in traditional curricula, continues to be understood. This way of conceiving learning does not allow methodological analysis of the design of integrated/integrative curricula that involve other ways of learning. Objective: To stimulate a theoretical and methodological reflection on curriculum integration in medical education, with the aim of orienting the design and assessment of integrated/integrative curricula and to discuss how innovative vertical and horizontal integrations are. Development: Horizontally and vertically integrated curricula are similar to traditional curricula fragmented in their design linear conception, while in systemic curricular integration, examples of which can be visualized in curricula designed through problem-based learning, curricular design is addressed in a circular way by connecting issues that feed back to one another; therefore, learning activities could be designed and assessed simultaneously. Conclusions: Thinking about curricular integration as a strategy of educational innovation implies discussing what we are understanding as integrated/ integrative curricula, how we are analyzing the practice of our medical curricula, with which theoretical frameworks we are doing that analysis, and what implications this has in curricula design and assessment(AU)