Prolonged chronic academic stress and its relationship with cytokine dysregulation in health science students.

Academic stress is a problem that affects students due to a number of factors that are considered stressors. These include academic overload and completion of assignments and exams, exacerbated by such external conditions as family, social and economic problems. Together, these can affect emotional and physical health, which may lead in the long term to developing a number of pathologies, given the alteration of immunological homoeostasis with which they are related. OBJECTIVE: To evaluate the effect of academic stress on the production of cytokines IL-6, TNF-α, IL-1ß and IL-10 in Morphology students in the Faculty of Health Sciences of the Universidad del Cauca during an academic period. METHODOLOGY: A descriptive longitudinal study was carried out with a population of 78 students studying Morphology, among the subjects with the highest academic load in the Physiotherapy, Medicine, Nursing and Phonoaudiology programs in the Faculty. Academic stress was assessed in the students by applying the Academic Stress Questionnaire (ASQ), and through quantification of the IL-6, TNF-α, IL-1ß and IL-10 cytokines using the ELISA (Enzyme-linked immunosorbent assay) technique in three "moments" of the academic semester: Moment 1: beginning of the academic semester; Moment 2: week of evaluations of 70% of the semester; Moment 3: week of final exams. RESULTS: The students perceived stress as "normal" at Moment 1, while at Moments 2 and 3 it was perceived as "quite a lot", with percentages of 48.7% and 50%, respectively. The predominant stressors were: "methodological deficiencies", "academic overload", and "exams", for the three moments of the study. "Physical exhaustion" was the most prevalent stress response at all three moments, followed by "irascible behaviour" (Moment 2 and 3), and "sleep disturbances" (Moment 3). To cope with the stress, the students resorted mainly to "planning and management of personal resources" in the three moments of the study. A progressive increase in the pro-inflammatory cytokines IL-6 and TNF-α and a decrease in IL-10 were observed at all three moments. A correlation was found between some questions belonging to the "methodological deficiencies", "beliefs about performance", "sleep disturbances", "physical exhaustion" and "irascible behaviour" dimensions with IL-6, IL-1ß, TNF-α and IL. -10. CONCLUSION: The morphology students suffer increased stress indicators (perceived stress and pro-inflammatory cytokines) throughout the academic period. The "methodological deficiencies", "academic overload" and "exams" stressors, together with "physical exhaustion", "sleep disturbances" and "irascible behaviour", possibly influence the production of the IL-6, TNF-α and IL-10 cytokines.

RIP2 Contributes to Expanded CD4+ T Cell IFN-γ Production during Efferocytosis of Streptococcus pneumoniae-Infected Apoptotic Cells.

Apoptotic cell clearance by professional and nonprofessional phagocytes in the process of efferocytosis is critical to preserve tissue homeostasis. Uptake of apoptotic cells by dendritic cells generates regulatory T cells and induces immunologic tolerance against self-antigens. In contrast, ingestion of infected apoptotic cells promotes activation of TLR4/MyD88-dependent bone marrow-derived dendritic cells (BMDCs) and triggers Th17 cell differentiation. In this study, we evaluated the impact of Streptococcus pneumoniae-infected apoptotic cell efferocytosis by BMDCs derived from C57BL/6 mice on differentiation and expansion of CD4+ T cell subsets, as well as the role of TLR2/4 and receptor-interacting protein 2 (RIP2) receptors in recognizing intracellular pathogens during efferocytosis. We demonstrated that BMDC-mediated efferocytosis of S. pneumoniae-infected apoptotic cells induced Th1 cell differentiation and expansion. Although TLR2/4 and RIP2 deficiency in BMDCs did not affect Th1 cell differentiation during efferocytosis, the absence of RIP2 decreased IFN-γ production by CD4 T cells during the expansion phase. These findings suggest that RIP2-mediated IL-1ß production during efferocytosis of S. pneumoniae-infected apoptotic cells partially supports a Th1-mediated IFN-γ production microenvironment.

Infección por Herpes virus Humano tipo 6 relacionado con manifestaciones dermatológicas y fatiga crónica: serie de casos / Human Herpesvirus type 6 infection related to dermatological manifestations and chronic fatigue: case series

Resumen Introducción: Las manifestaciones clínicas más frecuentes causadas por el Herpes Virus Humano Tipo 6 (HHV-6) ocurren en niños menores de 2 años, presentan lesiones en piel tipo roséola o exantema súbito. En adultos, las manifestaciones clínicas relacionadas a HHV-6 son muy variables, y pueden sobreponerse con otras afecciones. Objetivo: Presentar una serie de casos de pacientes diagnosticados con infección activa por HHV-6, quienes mostraban manifestaciones neurológicas, dermatológicas y de fatiga crónica. Materiales y métodos: Se realizó análisis de historias clínicas de 6 pacientes que fueron diagnosticados con infección activa por HHV-6, a través de métodos moleculares. Resultados: Se reportan 6 pacientes que fueron diagnosticados con infección activa por HHV-6 mediante métodos moleculares, quienes presentaron manifestaciones clínicas comunes tales como: fiebre, cefalea, depresión, decaimiento, pérdida de memoria y concentración, dolor fibromuscular, dolor poliarticular, sueño no reparador, exantema, nevus rubí, liquen plano y parestesias. Conclusiones: A través de esta serie de casos se espera resaltar la importancia de identificar la infección activa por HHV-6 a través de métodos moleculares, y sensibilizar a la comunidad médica sobre el papel que juega el virus en la evolución de diversas patologías.

Abstract Introduction: The most frequent clinical manifestations of Human Herpesvirus 6 (HHV-6) in children under 2 years of age are roseola-like skin lesions and sudden rash. In adults, the clinical manifestations associated with HHV-6 are highly variable and can overlap with other conditions. Objective: To present a case series of patients diagnosed with active HHV-6 infection, who showed neurological, dermatological and chronic fatigue manifestations. Materials and methods: An analysis of medical records of 6 patients who were diagnosed with active HHV-6 infection through molecular methods was performed. Results: 6 patients were diagnosed with active HHV-6 infection using molecular methods, who had common clinical manifestations such as fever, headache, depression, tiredness, loss of memory and concentration, fibromuscular pain, polyarticular pain, nonrestorative sleep, rash, ruby nevus, lichen planus and paresthesia. Conclusions: This case series highlights the importance of identifying active HHV-6 infection through molecular methods and creating awareness in the medical community of the role that the virus plays on the development of diverse pathologies.

Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals, improved with anti-human herpes virus treatment.

Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immunodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lymphocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient lymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diagnosis of profoundly CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings' health.

Múltiples enfermedades bacterianas, micóticas, parasitarias y virales pueden asociarse con linfocitopenia y linfocitopenia CD4+. También enfermedades autoinmunes, neoplásicas, inmunodeficiencia común variable, estrés físico, sicológico o traumático, la malnutrición y el tratamiento con inmunosupresores. Esta condición también se presenta sin causa aparente y es conocida como linfocitopenia T CD4+ idiopática. Entre las infecciones virales, los retrovirus, especialmente el virus de inmunodeficiencia humana, es la más frecuente causa, pero muchas otras infecciones virales agudas, entre ellas, la mononucleosis por citomegalovirus y por Epstein Barr virus, se asocian con linfocitopenia total y linfocitopenia T CD4+, que son transitorias y se recuperan cuando la enfermedad mejora. Una linfocitopenia grave asociada con infección crónica por virus herpes humanos y que mejore con el tratamiento de ellos, no ha sido publicada. Se describen 6 pacientes, negativos para virus de inmunodeficiencia humana, con linfocitopenia total y linfocitopenia T CD4+ graves y con manifestaciones clínicas de inmunodeficiencia celular, quienes respondieron rápidamente al tratamiento con ganciclovir o valganciclovir. Es importante considerar la infección crónica por virus herpes humanos en el diagnóstico diferencial de la etiología de la linfocitopenia T CD4+ en individuos no infectados por el virus de inmunodeficiencia humana, para iniciar un tratamiento efectivo de los pacientes y determinar en futuros estudios el impacto de la infección crónica por herpes virus en la salud humana.

Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals, improved with anti-human herpes virus treatment / Linfocitopenia T CD4+ grave, en individuos negativos para virus de immunodeficiencia humana, mejoró con tratamiento antivirus herpes humanos

Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immunodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lymphocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient lymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diagnosis of profoundly CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings' health.

Múltiples enfermedades bacterianas, micóticas, parasitarias y virales pueden asociarse con linfocitopenia y linfocitopenia CD4+. También enfermedades autoinmunes, neoplásicas, inmunodeficiencia común variable, estrés físico, sicológico o traumático, la malnutrición y el tratamiento con inmunosupresores. Esta condición también se presenta sin causa aparente y es conocida como linfocitopenia T CD4+ idiopática. Entre las infecciones virales, los retrovirus, especialmente el virus de inmunodeficiencia humana, es la más frecuente causa, pero muchas otras infecciones virales agudas, entre ellas, la mononucleosis por citomegalovirus y por Epstein Barr virus, se asocian con linfocitopenia total y linfocitopenia T CD4+, que son transitorias y se recuperan cuando la enfermedad mejora. Una linfocitopenia grave asociada con infección crónica por virus herpes humanos y que mejore con el tratamiento de ellos, no ha sido publicada. Se describen 6 pacientes, negativos para virus de inmunodeficiencia humana, con linfocitopenia total y linfocitopenia T CD4+ graves y con manifestaciones clínicas de inmunodeficiencia celular, quienes respondieron rápidamente al tratamiento con ganciclovir o valganciclovir. Es importante considerar la infección crónica por virus herpes humanos en el diagnóstico diferencial de la etiología de la linfocitopenia T CD4+ en individuos no infectados por el virus de inmunodeficiencia humana, para iniciar un tratamiento efectivo de los pacientes y determinar en futuros estudios el impacto de la infección crónica por herpes virus en la salud humana.