Salivary proteins offer insights into keratinocyte death during aphthous stomatitis. A case-crossover study.

BACKGROUND: The death of oral keratinocytes is a crucial step in the emergence of recurrent aphthous stomatitis (RAS, also known as aphthae or aphthous ulcers). Since there are no experimental models available to research aphthous ulcers, little is understood about this process. We hypothesize that saliva can be a data bank of information that offers insights on epithelial damage. METHODS: In this case-crossover study, we assessed the salivary proteome of patients with RAS (n = 36) in the presence and absence of ulcers using discovery proteomics and bioinformatics. Additionally, we contrasted these patterns with those of healthy individuals (n = 31) who had no prior aphthous ulceration. RESULTS: Salivary proteome showed that during the ulcerative phase, controlled cell death was downregulated. Due to its ability to distinguish between individuals with and without ulcers, the ATF6B protein raises the possibility that endoplasmic reticulum (ER) stress is responsible for the damage that leads to the death of oral keratinocytes. The high abundance of TRAP1 and ERN1 matches with this biological discovery. The type of death is immunogenic, according to the functional data found in a cell death database. CONCLUSION: We identified a cellular process that can lead to the death of oral keratinocytes in the etiopathogenesis process of RAS. Future studies should be conducted to identify what is responsible for the increase in ER stress signaling that would lead to an anti-cell death response.

Metformin Restrains the Proliferation of CD4+ T Lymphocytes by Inducing Cell Cycle Arrest in Normo- and Hyperglycemic Conditions.

CD4+ T lymphocytes play a key role in the modulation of the immune response by orchestrating both effector and regulatory functions. The effect of metformin on the immunometabolism of CD4+ T lymphocytes has been scarcely studied, and its impact under high glucose conditions, particularly concerning effector responses and glucose metabolism, remains unknown. This study aims to evaluate the effect of metformin on the modulation of the effector functions and glucose metabolism of CD4+ T lymphocytes under normo- and hyperglycemic conditions. CD4+ T lymphocytes, obtained from peripheral blood from healthy volunteers, were anti-CD3/CD28-activated and cultured for 4 days with three concentrations of metformin (0.1 mM, 1 mM, and 5 mM) under normoglycemic (5.5 mM) and hyperglycemic (25 mM) conditions. Effector functions such as proliferation, cell count, cell cycle analysis, activation markers and cytokine secretion were analyzed by flow cytometry. Glucose uptake was determined using the 2-NBDG assay, and levels of glucose, lactate, and phosphofructokinase (PFK) activity were assessed by colorimetric assays. Metformin at 5 mM restrained the cell counts and proliferation of CD4+ T lymphocytes by arresting the cell cycle in the S/G2 phase at the beginning of the cell culture, without affecting cell activation, cytokine production, and glucose metabolism. In fact, CD69 expression and IL4 secretion by CD4+ T lymphocytes was higher in the presence of 5 mM than the untreated cells in both glucose conditions. Overall, metformin inhibited proliferation through mechanisms associated with cell cycle arrest, leading to an increase in the S/G2 phases at the expense of G1 in activated CD4+ T lymphocytes in normo- and hyperglycemic conditions. Despite the cell cycle arrest, activated CD4+ T lymphocytes remained metabolically, functionally, and phenotypically activated.

High-intensity interval training reduces the induction of neutrophil extracellular traps in older men using live-neutrophil imaging as biosensor.

Neutrophil extracellular trap formation (NETosis) is a mechanism used by neutrophils to capture pathogens with their own DNA. However, the exacerbation of this immune response is related to serious inflammatory diseases. Aging is known to lead to an excessive increase in NETosis associated with various diseases. Under this scenario, the search for strategies that regulate the release of NETosis in older people becomes relevant. High-intensity interval training (HIIT) involves repeated bouts of relatively intense exercise with alternating short recovery periods. This training has shown beneficial effects on health parameters during aging and disease. However, little is known about the potential role of HIIT in the regulation of NETosis in healthy older people. The aim of this study was to evaluate the induction of NETosis by serum from healthy young and older men, before and after 12 weeks of HIIT using healthy neutrophils as a biosensor. HIIT was performed 3 times per week for 12 weeks in young (YOUNG; 21 ± 1 years, BMI 26.01 ± 2.64 kg⋅m-2, n = 10) and older men (OLDER; 66 ± 5 years, BMI 27.43 ± 3.11 kg⋅m-2, n = 10). Serum samples were taken before and after the HIIT program and NETosis was measured with live cell imaging in donated neutrophils cultured with serum from the participants for 30 h. Our results showed that serum from older men at baseline induced greater baseline NETosis than younger men (p < 0.05; effect size, ≥0.8), and 12 weeks of HIIT significantly reduced (Interaction Effect, p < 0.05; effect size, 0.134) the induction of NETosis in older men. In conclusion, HIIT is a feasible non-invasive training strategy modulating NETosis induction. Additionally, the use of neutrophils as a biosensor is an effective method for the quantification of NETosis induction in real time.

Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome.

Introduction: Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main pathways and long-term consequences attributed to this condition by analyzing clinical parameters and functional tests supported by machine learning and serum proteome profiling. Methods: Patients with L-TPD were classified according to the results of their computer-tomography (CT) scan and diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLCOc) tests at 4 and 12-months post-infection. Results: Regarding the acute phase, our data showed that L-TPD was favored in elderly patients with hypertension or insulin resistance, supported by pathways associated with vascular inflammation and chemotaxis of phagocytes, according to computer proteomics. Then, at 4-months post-infection, clinical and functional tests revealed that L-TPD patients exhibited a restrictive lung condition, impaired aerobic capacity and reduced muscular strength. At this time point, high circulating levels of platelets and CXCL9, and an inhibited FCgamma-receptor-mediated-phagocytosis due to reduced FcγRIII (CD16) expression in CD14+ monocytes was observed in patients with L-TPD. Finally, 1-year post infection, patients with L-TPD worsened metabolic syndrome and augmented body mass index in comparison with other patient groups. Discussion: Overall, our data demonstrated that CT scan and DLCOc identified patients with L-TPD after COVID-19. This condition was associated with vascular inflammation and impair phagocytosis of virus-antibody immune complexes by reduced FcγRIII expression. In addition, we conclude that COVID-19 survivors required a personalized follow-up and adequate intervention to reduce long-term sequelae and the appearance of further metabolic diseases.

Impact of Obstructive Sleep Apnea (OSA) in COVID-19 Survivors, Symptoms Changes Between 4-Months and 1 Year After the COVID-19 Infection.

Objective: To determine the association between Obstructive Sleep Apnea (OSA) with long-term symptoms and inflammatory cytokines, exploring the changes between 4-months and 1-year after COVID-19 infection. Methods: We conducted an observational, prospective cohort study, including patients ≥18 years old with confirmed diagnosis of COVID-19 between April to July 2020. All participants underwent two clinical follow-up visits, the first at 4-months (Visit 1) and the second at 1 year, after SARS-CoV-2 infection (Visit 2). Plasma glucose, total cholesterol, HDL, and triglycerides. Regarding pulmonary function, spirometry and lung diffusion capacity tests were assessed. For mental and neurocognitive evaluation, a short-form (SF-12), Beck depression and Hospital-Anxiety depression questionnaires were conducted at both time-points, whereas the Montreal Cognitive assessment was conducted during the second follow-up. Regarding to sleep evaluation, Epworth Sleepiness Scale, Insomnia Severity index and STOP-BANG questionnaire were conducted. Additionally, a home sleep apnea test and 7-day wrist actigraphy were performed in all participants. Inflammatory cytokines were measured using an inflammatory cytokine bead array kit. p-values < 0.05 were considered statistically significant and statistical analyses were performed using R software. Results: A total of 60 patients were included in the first follow-up, from which 57 completed the second follow-up. The mean age was 46.4 years-old (SD ± 13.1) and 53.3% were male. 30% of cases reported mild COVID-19 infection, 28.3% with moderate illness, and 41.6% with severe illness. Moreover, 56.6% of them were admitted to the ICU. Regarding to metabolic values, the OSA group showed higher values of insulin resistance (IR) (27%), systolic blood pressure (SBP) 135.2 (±19.1), dyslipidemia (67.5%), total cholesterol 202.1 (±60.5), triglycerides 176.1 (±119.0) and HOMA-IR 9.0 (±18.8) in comparison with the non-OSA group. 1 year after COVID-19 infection, DLCO test remains abnormal in OSA patients (25% OSA vs. 3.6% non-OSA, p = 0.02). Finally, those participants with OSA who develop ARDS reported an adjusted OR 20.4 (95%-CI, 1.04-504) risk of neurocognitive impairment. Discussion: Among patients with previous COVID-19, OSA impact the development of incident glycemic, neurocognitive impairment, and abnormal functional pulmonary changes that persist up to 1 year since acute phase.

[Orange juice residues as dietary fiber source for foods]. / Utilización de residuos de la industria de jugos de naranja como fuente de fibra dietética en la elaboración de alimentos.

Food snacks using powdered residues from the orange juice industry as a source of dietary fiber were formulated. Six formulations utilizing powdered orange residues with three different moisture levels (25%, 15% and 10%) were elaborated. There were used two basic blends. The first one was 33.3% of orange dry powder, 33.3% of honey, 16.6% of roasted peanut, 16.6% of raisins; the second one was 28.6% of orange powder, 35.7% of honey, 17.85% of roasted peanut, 17.85% of raisins. Snacks had spherical shape with 2.5 cm diameter and a weight close to 10g. The snack moisture was between 12.6 and 17.4%, and their aw between 0.65 and 0.71. The snack chemical composition, on dry matter basis, was 1.6 and 1.9% of ash; 12.3 and 15.2% of lipids; 6.1 and 7.1% of proteins; and 56.2 to 59.6% of carbohydrates; the caloric contribution (calculated) was between 326.8 and 342.9 kcal/100g. The powdered orange residue had 64% of total dietary fiber, 54% of insoluble dietary fiber and 10% of soluble dietary fiber. In the snack the fiber amount fluctuated between 20 and 26% of total dietary fiber; 18 and 22% of insoluble dietary fiber, and 3.0 and 4.5% of soluble dietary fiber. The snack with the higher content of orange residue presented the higher content of dietary fiber. The snacks were well accepted by a sensory panel, without showing differences among treatments.

Utilización de residuos de la industria de jugos de naranja como fuente de fibra dietética en la elaboración de alimentos / Orange juice residues as dietary fiber source for foods

En este trabajo se plantea la formulación de un alimento tipo"snack" utilizando residuos en polvo provenientes de la industria procesadora de jugo de naranja, como fuente de fibra dietética. Para ello se elaboraron 6 formulaciones, utilizando el polvo con 3 niveles de humedad (25, 15 y 10%) que se incorporó a 2 mezclas, una compuesta por un 33,3% de polvo de naranja, 33,3% de miel, 16,6% de maní tostado y molido y 16,6% de pasas molidas y otra compuesta por un 28,6% de polvo de naranja, 35,7% de miel, 17,85% de maní y 17,85% de pasas. El residuo de naranja presentó un contenidode 64% de fibra dietética total, 54% fibra dietética insoluble y 10% fibra dietética soluble. Los "snack" tuvieron forma esférica con 2,5cm de diámetro y 10g de peso; una humedad que fluctuó entre 12,6 y 17,4%, y una actividad de agua entre 0,65 a 0,71. La composición proximal (base materia seca), fluctuó entre 1,6 y 1,9% de cenizas; 12,3 y 15,2% de lípidos; 6,1 y 7,1% de proteínas y 56,2 a 59,6% de hidratos de carbono con 326,8 a 342,9 Kcal/100g de producto. El aporte de fibra en los "snack" fluctuó entre un 20 a 26% de fibra dietética total, 18 a 22% de fibra dietética insoluble y 3,0 a 4,5% de fibra dietética soluble. El "snack" con mayor contenido de polvo de naranja presentó el mayor contenido de fibra dietética. Los "snack" fueron bien aceptados por el panel de evaluación sensorial sin registrar diferencias significativas entre los distintos tratamientos.

Orange juice residues as dietary fiber source for foods. Food snacks using powdered residues from the orange juice industry as a source of dietary fiber were formulated. Six formulations utilizing powdered orange residues with three different moisture levels (25%, 15% and 10%) were elaborated. There were used two basic blends. The first one was 33.3% of orange dry powder, 33.3% of honey, 16.6% of roasted peanut, 16.6% of raisins; the second one was 28.6% of orange powder, 35.7% of honey, 17.85% of roasted peanut, 17.85% of raisins. Snacks had spherical shape with 2.5 cm diameter and a weight close to 10g. The snack moisture was between 12.6 and 17.4%, and their aw between 0.65 and 0.71. The snack chemical composition, on dry matter basis, was 1.6 and 1.9% of ash; 12.3 and 15.2% of lipids; 6.1 and 7.1% of proteins; and 56.2 to 59.6% of carbohydrates; the caloric contribution (calculated) was between 326.8 and 342.9 kcal/100g. The powdered orange residue had 64% of total dietary fiber, 54% of insoluble dietary fiber and 10% of soluble dietary fiber. In the snack the fiber amount fluctuated between 20 and 26% of total dietary fiber; 18 and 22% of insoluble dietary fiber, and 3.0 and 4.5% of soluble dietary fiber. The snack with the higher content of orange residue presented the higher content of dietary fiber. The snacks were well accepted by a sensory panel, without showing differences among treatments.

Fractura de peñasco: revisión de once casos / Temporal bone fracture: 11 cases review

Los autores presentan su experiencia clínica en 11 pacientes con fractura de peñasco, en los cuales se estudió su presentación clínica, compromiso auditivo, vestibular y manifestaciones radiológicas en la tomografía axial computarizada (TAC). Su sintomatología más frecuente fue la hipoacusia y en el examen clínico de ingreso la otorragia acompañada de hemotímpano, desnivel en la región postero-superior del conducto auditivo externo y laceración timpánica. La TAC mostró con mayor frecuencia signos indirectos de fractura de peñasco. Los pacientes se siguieron por 9 meses como promedio, quedando 6 de ellos con secuelas que fueron hipoacusia, vértigo y paresia facial