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Background: Suicide and suicidal behaviors were already a global public health problem, producing preventable injuries and deaths. This issue may worsen due to the COVID-19 pandemic and may differentially affect vulnerable groups in the population, including children, adolescents, and young adults. The current study evaluated the association of affective variables (depression, hopelessness, and anxiety), drug use (alcohol, tobacco, and others), emotional intelligence, and attachment with suicidal behaviors. Methods: A state-wide survey included 8033 students (51% female, 49% male, mean age of 16 years) from science and technology high-schools using a standardized questionnaire that was distributed online. Multinomial logistic regression models tested associations between suicidal behaviors and several covariates. The analyses accommodated the complex structure of the sample. Results: Approximately 21% of all students reported a suicidal behavior (11% with a low-lethality suicide attempt, 6% with self-injuries, and 4% with a high-lethality suicide attempt). Variables associated with higher odds of suicidal behavior included: female sex, depression, hopelessness, anxiety, alcohol and tobacco use, childhood trauma, and having to self-rely as issues affecting attachment, and low self-esteem. Security of attachment was associated with lower odds of suicidal behavior. Conclusions: The complexity of suicidal behavior makes it clear that comprehensive programs need to be implemented.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae mainly affecting skin and peripheral nerves. Leprosy has a broad range of clinical manifestations that range from mild (tuberculoid leprosy) to severe (lepromatous leprosy) forms, and are highly dependent on the host's immune response. Among the immune response elements involved in the pathogenesis of leprosy are the Toll-like receptors (TLRs), vitamin D receptor (VDR), natural killer cells (NK), and T cells. These innate and adaptive immune response elements may be related to the Notch signaling pathway, which is involved in immune cell growth, differentiation, and proliferation. We hypothesize that failure in Notch signaling in leprosy patients may be associated to: 1) compromising NK cell maturation, lysing of infected cells, and CD4+ Th1 differentiation. 2) VDR alterations and TLR polymorphisms may affect expression of Notch Delta-like ligands (DLL) in antigen presenting cells (APCs). 3) altered DLL expression by APCs could compromise CD4+ T cell differentiation towards the Th1 and Th17 effector phenotypes; and finally 4) expression of Notch Jagged ligands would induce CD4+ T cell differentiation towards Th2 effector phenotype and alternative activation of macrophages. Altogether, these signaling failures could favor proliferation of M. leprae in the host. Therefore, evidence of the proposed immunologic failures in leprosy patients would be essential for the better understanding of immunopathogenesis of this disease, and would ultimately enable detection of susceptible individuals, providing a valuable tool for prevention of this debilitating disease.

Background: : The diversity of the HIV proteome influences the cellular response and development of an effective vaccine, particularly due to the generation of viral variants with mutations located within CD8+ T-cell epitopes. These mutations can affect the recognition of the epitopes, that may result in the selection of HIV variants with mutated epitopes (autologous epitopes) and different CD8+ T-cell functional profiles. Objective:: To determine the phenotype and functionality of CD8+ T-cell from HIV-infected Colombian patients in response to autologous and consensus peptides derived from HIV-1 clade B protease and reverse transcriptase (RT). Methods:: By flow cytometry, we compared the ex vivo CD8+ T-cell responses from HIV-infected patients to autologous and consensus peptides derived from HIV-1 clade B protease and RT, restricted by HLA-B*35, HLA-B*44 and HLA-B*51 alleles. Results:: Although autologous peptides restricted by HLA-B*35 and HLA-B*44 did not show any differences compared with consensus peptides, we observed the induction of a higher polyfunctional profile of CD8+ T-cells by autologous peptides restricted by HLA-B*51, particularly by the production of interferon-γ and macrophage inflammatory protein-1β. The response by different memory CD8+ T-cell populations was comparable between autologous vs. consensus peptides. In addition, the magnitude of the polyfunctional response induced by the HLA-B*51-restricted QRPLVTIRI autologous epitope correlated with low viremia. Conclusion:: Autologous peptides should be considered for the evaluation of HIV-specific CD8+ Tcell responses and to reveal some relevant epitopes that could be useful for therapeutic strategies aiming to promote polyfunctional CD8+ T-cell responses in a specific population of HIV-infected patients.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. This disease is characterized by skin and peripheral nerve trunk damage. The mechanisms responsible for the observed nerve damage in leprosy could be directly related to the ability of M. leprae to infect Schwann cells, leading to triggering of signaling events. Therefore, we hypothesize that in response to M. leprae infection, activation of the Notch signaling pathway in Schwann cells could play a crucial role in glial cell dedifferentiation. On the other hand, nerve damage evidenced in this disease may be additionally explained by indirect mechanisms such as the immune response and genetic susceptibility of the host. The understanding of the mechanisms leading to nerve damage induced by M. leprae infection will allow us to generate valuable tools for the early detection of leprosy as well as for the mitigation of the effects of this disabling disease.

Numerous reports have focused on consensus peptides to determine CD8+ T-cell responses; however, few studies evaluated the functional profile using peptides derived from circulating strains of a specific region. We determined the effector profile and maturation phenotype of CD8+ T-cells targeting the consensus APPEESFRS (AS9) epitope and its variant APPEESFRF (AF9), previously identified. The free energy of binding, maturation phenotype, and polyfunctional profile of both peptides were similar. The magnitude of CD8+ T-cell responses to AF9 was greater than the one elicited by AS9, although the difference was not significant. The polyfunctional profile of AF9 was characterized by CD107a/interleukin-2 (IL-2)/macrophage inflammatory protein beta (MIP1β) and by interferon gamma (IFNγ)/MIP1β/tumor necrosis factor alpha (TNFα) in response to AS9. TNFα production was significantly higher in response to AF9 than to AS9, and there was a negative correlation between the absolute number of CD8+ T-cell-producing TNFα and the plasma human immunodeficiency virus (HIV) load, suggesting a role of this cytokine in the control of HIV replication.

La infección con el virus de la inmunodeficiencia humana (VIH-1) sigue siendo un problema de salud pública. Hasta la fecha, considerando la importancia que tiene los linfocitos T CD8+ (LTCD8+) en el control de la replicación viral, algunas estrategias terapéuticas se han enfocado en la inducción de la respuesta de LTCD8+ específicos de péptidos derivados de la proteí-na de Gag. El desarrollo de estas estrategias requiere la identificación de epítopes inmunodominantes de cepas virales circulantes, su interacción con las molé-culas del HLA-I de alta frecuencia en cada población, y su efecto sobre la calidad de la respuesta de los LTCD8+. Una de las principales dificultades para el desarrollo de estas estrategias es el fenómeno de escape inmunológi-co, donde un cambio en un aminoácido dentro de un epítope puede afectar la unión del péptido a la molé-cula del HLA-I, el reconocimiento por el TCR y la gene-ración de una respuesta efectiva por parte del LTCD8+. En un estudio previo, en una cohorte de pacientes infectados con VIH-1 de la ciudad de Medellín, se evidenció la adaptación de cepas circulantes del VIH-1 a las moléculas HLA-I más prevalentes de la población (HLA-A*02 y HLA-B*35), a través de la identificación de mutaciones bajo selección positiva localizadas en epítopes derivados de la proteína Gag (GC9, SL9 y HY9, HA9, respectivamente); además, a través de una predicción in silico se evaluó si las mutaciones encontradas tenían una mayor o una menor afinidad al HLA-I. Si bien esta estrategia permitió predecir la interacción entre péptidos mutados y HLA-I, se desco-noce cuál es la respuesta funcional de los LTCD8+ que pueden inducir estos péptidos.