Diagnostic Performance of Serum MicroRNAs for ST-Segment Elevation Myocardial Infarction in the Emergency Department.

Prompt diagnosis of ST-segment elevation myocardial infarction (STEMI) is essential for initiating timely treatment. MicroRNAs have recently emerged as biomarkers in cardiovascular diseases. This study aimed to evaluate the discriminatory capacity of serum microRNAs in identifying an ischemic origin in patients presenting with chest discomfort to the Emergency Department. The study included 98 participants (78 with STEMI and 20 with nonischemic chest discomfort). Significant differences in the expression levels of miR-133b, miR-126, and miR-155 (but not miR-1, miR-208, and miR-208b) were observed between groups. miR-133b and miR-155 exhibited 97% and 93% sensitivity in identifying STEMI patients, respectively. miR-126 demonstrated a specificity of 90% in identifying STEMI patients. No significant associations were found between microRNAs and occurrence of major adverse cardiovascular events (MACE). However, patients with MACE had higher levels of interleukin (IL)-15, IL-21, IFN-γ-induced protein-10, and N-terminal pro B-type natriuretic peptide compared to non-MACE patients. Overall, there were significant associations among the expression levels of microRNAs. However, microRNAs did not demonstrate associations with either inflammatory markers or cardiovascular risk scores. This study highlights the potential of microRNAs, particularly miR-133b and miR-126, as diagnostic biomarkers for distinguishing patients with STEMI from those presenting with nonischemic chest discomfort to the Emergency Department.

Dengue vaccine acceptability before and after the availability of COVID-19 vaccines in Puerto Rico.

Dengue is a growing public health threat, causing approximately 400 million infections annually. In June 2021, the Advisory Committee on Immunization Practices recommended the first dengue vaccine (CYD-TDV) for children aged 9-16 years with a previous dengue infection, living in endemic areas, such as Puerto Rico (PR). As the COVID-19 pandemic affected vaccine intention worldwide, we assessed dengue vaccine intention before (pre-COVID) and after (post-COVID) COVID-19 vaccine availability among participants enrolled in the Communities Organized to Prevent Arboviruses (COPA) cohort to prepare for dengue vaccine implementation in PR. We used logistic regression models to evaluate changes in dengue vaccine intention by interview timing and participant characteristics. Among 2,513 participants pre-COVID, 2,512 answered the dengue vaccine intention question for themselves, and 1,564 answered relative to their children. Post-COVID, dengue vaccine intention in adults increased for themselves from 73.4% to 84.5% (adjusted odds ratio (aOR) = 2.27, 95%CI: 1.90-2.71) and relative to their children from 75.6% to 85.5% (aOR = 2.21, 95%CI: 1.75-2.78). Among all participants, groups with higher dengue vaccine intention included those who reported previous year influenza vaccine uptake and those who reported being frequently bitten by mosquitos, compared to those who did not. Adult males were also more likely to intend to vaccinate themselves than females. Respondents who were employed or in school were less likely to intend to vaccinate compared to those who were not working. The primary reasons for vaccine hesitancy were concerns with side effects and not believing in vaccines, which should be considered during educational strategies prior to dengue vaccine implementation. In general, dengue vaccine intention is high in PR and has increased after COVID-19 vaccine availability, potentially due to increased awareness of vaccine importance during the COVID-19 pandemic.

Senescent CD4+CD28null cells are increased in chronic hyperuricemia, show aberrant effector phenotypes, and are reversed after allopurinol therapy: a proof-of-concept pilot study.

To characterize CD4+CD28null cells in chronic hyperuricemia and investigate whether allopurinol could restore CD28 expression and the balance of T helper phenotypes. Asymptomatic individuals with chronic hyperuricemia and ultrasonographic findings evocative of urate deposition in the joints. Age- and gender-matched normouricemic individuals were also studied. Oral allopurinol at 150 mg/day for 4 weeks, followed by 300 mg/day through week 12. Color-flow cytometry on peripheral blood mononuclear cells (PBMC) with antibodies against CD4, CD28, T-bet (Th1), GATA-3 (Th2), and RORγt (Th17). Six patients (five men, median age of 53 years) and seven controls were studied. At baseline, hyperuricemic patients had more CD4+CD28null/CD4+ cells than normouricemic subjects (36.8% vs. 6.1%; p = 0.001), with a predominance of T-bet+ cells (98.5% vs. 6.6%; p = 0.001) and few RORγt+ cells (0.7% vs. 89.4%; p = 0.014). In hyperuricemic patients, the number of CD4+ cells/10,000 PBMC was similar before and after allopurinol (3378 vs. 3954; p = 0.843). Conversely, CD4+CD28null cells decreased from 36.8% (23.0-43.7) to 15.8% (4.7-28.1; p = 0.031). CD4+CD28nullT-bet+ cells decreased from 98.5% (95.0-99.4) to 88.3% (75.2-98.9; p = 0.062), CD4+CD28nullGATA-3+ cells increased from 0% (0-4.0) to 2.8% (0.1-15.6; p = 0.156), and CD4+CD28nullRORγt+ cells increased from 0.7% (0.4-7.0) to 4.5% (1.3-28.1; p = 0.031). The CD4+CD28null cell subset is abnormally expanded in chronic hyperuricemia, despite the absence of overt urate-related disease. Allopurinol may partially restore CD28 expression on CD4+ cells while enhancing the homeostatic balance of T helper phenotypes. ClinicalTrials.gov, number NCT04012294.

The prognostic importance of the angiotensin II/angiotensin-(1-7) ratio in patients with SARS-CoV-2 infection.

BACKGROUND: Information about angiotensin II (Ang II), angiotensin-converting enzyme 2 (ACE2), and Ang-(1-7) levels in patients with COVID-19 is scarce. OBJECTIVE: To characterize the Ang II-ACE2-Ang-(1-7) axis in patients with SARS-CoV-2 infection to understand its role in pathogenesis and prognosis. METHODS: Patients greater than 18 years diagnosed with COVID-19, based on clinical findings and positive RT-PCR test, who required hospitalization and treatment were included. We compared Ang II, aldosterone, Ang-(1-7), and Ang-(1-9) concentrations and ACE2 concentration and activity between COVID-19 patients and historic controls. We compared baseline demographics, laboratory results (enzyme, peptide, and inflammatory marker levels), and outcome (patients who survived versus those who died). RESULTS: Serum from 74 patients [age: 58 (48-67.2) years; 68% men] with moderate (20%) or severe (80%) COVID-19 were analyzed. During 13 (10-21) days of hospitalization, 25 patients died from COVID-19 and 49 patients survived. Compared with controls, Ang II concentration was higher and Ang-(1-7) concentration was lower, despite significantly higher ACE2 activity in patients. Ang II concentration was higher and Ang-(1-7) concentration was lower in patients who died. The Ang II/Ang-(1-7) ratio was significantly higher in patients who died. In multivariate analysis, Ang II/Ang-(1-7) ratio greater than 3.45 (OR = 5.87) and lymphocyte count ⩽0.65 × 103/µl (OR = 8.43) were independent predictors of mortality from COVID-19. CONCLUSION: In patients with severe SARS-CoV-2 infection, imbalance in the Ang II-ACE2-Ang-(1-7) axis may reflect deleterious effects of Ang II and may indicate a worse outcome.

Should a recent SARS-CoV-2 infection be considered a risk or prognostic factor for ST-segment elevation myocardial infarction?

Objective: The aim of the study was to assess whether a recent SARS-CoV-2 infection could by itself be a risk or prognostic factor for ST-segment elevation myocardial infarction (STEMI). Method: An observational study in unvaccinated patients with STEMI confirmed by cardiac catheterization was conducted. A recent or concurrent SARS-CoV-2 infection was identified by the presence of serum IgG against the nucleocapsid protein, or a positive polymerase chain reaction test on nasopharyngeal swabs. Baseline cardiovascular risk factors, clinical STEMI severity, main catheterization findings, and occurrence of major adverse cardiovascular events (MACE) during hospitalization were compared between study subgroups. Results: Of a total of 89 patients recruited, 14 (16%) had a recent SARS-CoV-2 infection. Patients with STEMI and recent SARS-CoV-2 infection had a markedly lower frequency of high blood pressure (20% versus 55%; P = 0.03) as well as a tendency to have fewer comorbidities. Regarding the clinical presentation, there were no differences in the severity of the STEMI. Furthermore, the main findings during cardiac catheterization including the atherosclerotic burden and the number of vessels affected, as well as the occurrence of MACE during follow-up, were not significantly different between the groups. Conclusions: A recent SARS-CoV-2 infection appears to facilitate the triggering of STEMI, as these patients have fewer traditional cardiovascular risk factors than their uninfected counterparts. However, this does not seem to affect the clinical presentation or the in-hospital course of STEMI patients.

Elevated Levels of Soluble CD147 are Associated with Hyperinflammation and Disease Severity in COVID-19: A Proof-of-Concept Clinical Study.

To evaluate soluble CD147 levels in COVID-19 and identify whether these are associated with hyperinflammation and disease severity. One-hundred and nine COVID-19 patients and 72 healthy blood donors were studied. Levels of CD147, matrix metalloproteases (MMP) and inflammatory markers were measured on hospital arrival, while the need for mechanical ventilation and the occurrence of death during hospitalization were recorded. CD147 levels were higher in COVID-19 (1.6, 1.0-2.3 vs 1.3, 1.0-1.6 ng/ml; P = 0.003) than controls. MMP-2 (9.2, 4.5-12.9 vs 4.2, 3.7-4.6 ng/ml; P < 0.001), MMP-3 (1.1, 0.9-1.3 vs 0.9, 0.7-1.0 ng/ml; P < 0.001) and MMP-9 (0.9, 0.5-1.2 vs 0.4, 0.2-0.6 ng/ml; P < 0.001) were also higher in COVID-19, while MMP-1 (0.6, 0-1.4 vs 0.6, 0.3-0.7 ng/ml; P = 0.711) was not different. Significant correlations were found between CD147 and MMP-2 (ρ = 0.34), MMP-3 (ρ = 0.21), interleukin 6 (ρ = 0.21), and the neutrophil/lymphocyte ratio (ρ = 0.26). Furthermore, CD147 levels were higher in patients who required mechanical ventilation (1.8, 1.4-2.4 vs 1.2, 0.8-1.9 ng/ml; P < 0.001) and in those who ultimately died (1.9, 1.4-2.7 vs 1.4, 0.9-1.9 ng/ml; P = 0.009). CD147 is elevated in COVID-19 and appears to contribute to hyperinflammation and disease severity.

Usefulness of Easy-to-Use Risk Scoring Systems Rated in the Emergency Department to Predict Major Adverse Outcomes in Hospitalized COVID-19 Patients.

BACKGROUND: Several easy-to-use risk scoring systems have been built to identify patients at risk of developing complications associated with COVID-19. However, information about the ability of each score to early predict major adverse outcomes during hospitalization of severe COVID-19 patients is still scarce. METHODS: Eight risk scoring systems were rated upon arrival at the Emergency Department, and the occurrence of thrombosis, need for mechanical ventilation, death, and a composite that included all major adverse outcomes were assessed during the hospital stay. The clinical performance of each risk scoring system was evaluated to predict each major outcome. Finally, the diagnostic characteristics of the risk scoring system that showed the best performance for each major outcome were obtained. RESULTS: One hundred and fifty-seven adult patients (55 ± 12 years, 66% men) were assessed at admission to the Emergency Department and included in the study. A total of 96 patients (61%) had at least one major outcome during hospitalization; 32 had thrombosis (20%), 80 required mechanical ventilation (50%), and 52 eventually died (33%). Of all the scores, Obesity and Diabetes (based on a history of comorbid conditions) showed the best performance for predicting mechanical ventilation (area under the ROC curve (AUC), 0.96; positive likelihood ratio (LR+), 23.7), death (AUC, 0.86; LR+, 4.6), and the composite outcome (AUC, 0.89; LR+, 15.6). Meanwhile, the inflammation-based risk scoring system (including leukocyte count, albumin, and C-reactive protein levels) was the best at predicting thrombosis (AUC, 0.63; LR+, 2.0). CONCLUSIONS: Both the Obesity and Diabetes score and the inflammation-based risk scoring system appeared to be efficient enough to be integrated into the evaluation of COVID-19 patients upon arrival at the Emergency Department.

A simple and readily available inflammation-based risk scoring system on admission predicts the need for mechanical ventilation in patients with COVID-19.

OBJECTIVE: To investigate whether a simplified inflammation-based risk scoring system comprising three readily available biomarkers (albumin, C-reactive protein, and leukocytes) may predict major adverse outcomes in patients with COVID-19. METHODS: Upon admission to the emergency room, the inflammation-based risk scoring system was applied and patients were classified as having mild, moderate, or severe inflammation. In-hospital occurrence of thrombosis, need for mechanical ventilation, and death were recorded. RESULTS: One-hundred patients (55 ± 13 years; 71% men) were included and classified as having mild (29%), moderate (12%), or severe (59%) inflammation. The need for mechanical ventilation differed among patients in each group (16%, 50%, and 71%, respectively; P < 0.0001), yielding a 4.1-fold increased risk of requiring mechanical ventilation in patients with moderate inflammation and 5.4 for those with severe inflammation. On the contrary, there were no differences for the occurrence of thrombosis (10%, 8%, and 22%, respectively; P = 0.142) or death (21%, 42%, and 39%, respectively; P = 0.106). In the multivariate analysis, only severe inflammation (hazard ratio [HR] = 4.1), D-dimer > 574 ng/mL (HR = 3.0), and troponin I ≥ 6.7 ng/mL (HR = 2.4) at hospital admission were independent predictors of the need for mechanical ventilation. CONCLUSION: The inflammation-based risk scoring system predicts the need for mechanical ventilation in patients with severe COVID-19.

Quiste de bolsa de Rathke e hiperprolactinemia, una causa infrecuente de amenorrea primaria / Rathke cleft cysts and hyperprolactinemia, an uncommon cause of primary amenorrhea

El quiste de la bolsa de Rathke es una lesión epitelial benigna de la región selar, formada a partir de remanentes embrionarios. La mayoría de los casos son asintomáticos, aunque pudiera presentarse con cefalea, disfunción hipofisaria y trastornos visuales, muy infrecuentemente como apoplejía hipofisaria. Se presenta el caso de una paciente que, habiendo presentado amenorrea primaria, se le realiza el diagnóstico de quiste de la bolsa de Rathke con hiperprolactinemia, logrando menarquia luego del tratamiento con cabergolina.

Rathke's cyst is a benign epithelial lesion of the sellar region, formed from embryonic remnants. Most cases are asymptomatic although it could present with headache, pituitary dysfunction and visual disorders, very infrequently as pituitary stroke. We present the case of a patient who, having presented primary amenorrhea, is diagnosed with Rathke's cyst with hyperprolactinemia, achieving menarche after treatment with cabergoline.

Disgenesia gonadal pura 46 XX, una causa infrecuente de hipogonadismo: presentación de un caso / Pure gonadal dysgenesis 46 XX, an ucommon cause of hypogonadism: case presentation

El término disgenesia gonadal pura hace referencia a mujeres fenotípicas con infantilismo sexual, amenorrea primaria, hábito eunucoide y un cariotipo 46, XX o 46, XY sin anomalías cromosómicas. Puede asociarse a complicaciones como osteoporosis y síndrome metabólico, elevando el riesgo cardiovascular. Se presenta una paciente femenina de 16 años y 8 meses de edad que acude a consulta de endocrinología por presentar amenorrea primaria.

The term pure gonadal dysgenesis refers to phenotypic women with sexual infantilism, primary amenorrhea an d the eunucoid habit and a 46, XX or 46, XY karyotype without chromosomal abnormalities. It can be associated with complications such as osteoporosis and metabolic syndrome, increasing cardiovascular risk. We present a female patient of 16 years and 8 months of age who attended endocrinology clinic for presenting primary amenorrea.

Acromegalia y silla turca vacía: una asociación infrecuente: presentación de un caso / Acromegaly and empty sella syndrome: an infrequent association: presentation of a case

La acromegalia, originada por un exceso de producción de Hormona de crecimiento (Gh), se caracteriza por crecimiento somático exagerado, alto riesgo cardio-metabólico, así como reducción de la expectativa de vida. Tiene una incidencia de 3-4 casos por millón de habitantes. El diagnóstico se retrasa hasta 10 años aumentando la morbi-mortalidad. Las alternativas terapéuticas incluyen medicamentos y cirugía, que van encaminados a reducir los efectos de masa tumoral, normalizar los parámetros bioquímicos y resolver las manifestaciones clínicas. En casos muy infrecuentes, el tumor hipofisario que la origina se asocia a silla turca vacía.

Acromegaly, caused by an excess production of growth hormone (Gh), it is characterized by exaggerated somatic growth, high cardio-metabolic risk, as well as reduction of life expectancy. It has an incidence of 3-4 cases per million population. The diagnosis is delayed up to 10 years increasing morbidity and mortality. The therapeutic alternatives include medications and surgery, which are aimed at reduce the effects of tumor mass, normalize biochemical parameters and resolve clinical manifestations. In very infrequent cases, the pituitary tumor that originates it is associated with empty sella syndrome. Key words: Acromegaly, Empty sella syndrome, Pituitary tumor.

A novel performing PEG-cholane nanoformulation for Amphotericin B delivery.

A novel formulation for amphotericin B (AmB) delivery has been developed using micelle-forming 5 kDa monomethoxy-polyethylene glycol functionalized with cholanic acid (PEG 5kDa-cholane). This polymer was found to increase 10(3) times the AmB solubility with a 12:1 AmB/PEG5 kDa-cholane molar ratio (2:1 w/w ratio). Dynamic light scattering and transmission electron microscopy analyses showed that PEG5 kDa-cholane associated with AmB to form 30 nm micelles. Isothermal titration calorimetry analyses performed at different pH showed that PEG 5kDa-cholane interacts with AmB according to multiple-site association profiles. Affinity constants and enthalpy and entropy changes were found to depend on pH, suggesting that the polymer interaction depends on the AmB ionization and aggregation. The freeze-dried product could be promptly re-dispersed forming a colloidal dispersion with the biopharmaceutical features of the freshly prepared micelles, namely AmB solubility and micelle size. The dispersion was stable over one month incubation at room temperature. FT-infrared spectrometry, differential scanning calorimetry and X-ray diffractometry showed that in the freeze-dried product, AmB intimately interacts with PEG 5kDa-cholane. In presence of serum albumin, AmB formulated with PEG 5kDa-cholane was found to undergo less extensive and slower disaggregation than in Fungizone(®). Antifungal activity studies performed using Candida albicans showed that AmB/PEG 5kDa-cholane was 15% more active than AmB in buffer.

Simple one-step ultrasonic synthesis of anatase titania/polypyrrole nanocomposites.

In this work, hybrid nanocomposites based on anatase titania:polypyrrole (TiO(2):PPy) were directly obtained from a simple, one-step, ultrasonic (UT)-assisted synthesis. The properties of these crystalline nanocomposites were compared with those of others fabricated using cold (Cold)-assisted synthesis without any UT assistance, which required a hydrothermal treatment (HT) to yield crystalline anatase titania in the nanocomposite (TiO(2):PPy) at low temperature (130°C) and in a short time (3h). The SEM results demonstrated that the UT-assisted synthesis is a feasible method to obtain anatase TiO(2):PPy nanocomposites with controlled morphology using low energy. The Fourier transform infrared (FT-IR) bands of the crystalline nanocomposites exhibited a shift with respect to neat components, which was attributed to the strong interaction between the secondary amine groups (N-H) of PPy and the oxygen from TiO(2). The acceptable absorption in the visible region (λ(max)=670nm) indicates that these nanocomposites are good candidates for harvesting energy in solar cells. Devices based on these nanocomposites were built to evaluate their electrical properties. An increase in the photocurrent was observed for the devices prepared with the nanocomposites from the UT-assisted synthesis.

Physiological-enzymatic characteristics and inoculation of mycelial strains of Descolea antarctica Sing. in Nothofagus seedlings

At present, reforestation has focused on native forests with anthropogenic intervention and eroded soils. There is interest in producing Nothofagus seedlings which can overcome adverse conditions encountered on reforestation sites. It is necessary to find new fungi that can be utilized as mycorrhizal inoculants and that enable the seedlings to increase their tolerance to adverse conditions. Two ectomycorrhizal strains of the fungus Descolea antarctica (D1 and D2) were cultured at different temperatures, pH levels and the activities of amylases, cellulases, and phosphatases were determined. In greenhouse and nursery trials, the growth responses of inoculated Nothofagus obliqua seedlings were evaluated. D1 and D2 exhibited the highest growth rates at 23ºC. Both strains grew at pH levels from 4 to 11. The highest enzymatic activities were registered for amylase (57.2 mg glucose/ml g of mycelium hr) and acid phosphatases (58.1 mg p-nitrophenol/ml g of mycelium hr) at 37ºC, and acid phospatases (1.720 mg p-nitrophenol/ml of mycelium hr) and alkaline phosphatases (1.360 mg p-nitrophenol/ml g of mycelium hr) at pH 4 and pH 11, respectively. We conclude that suitable N. obliqua seedlings for use in reforestation were obtained using D2 as inoculant.

Disfunción autonómica cardíaca en diabetes mellitus / Autonomic cardiac dysfunction at Diabetes Mellitus

Objetivo: Evaluar la prevalencia de cardiopatía autonómica (CA) en pacientes con Diabetes Mellitus asistidos en consultorio externo. Material y Método: Desde julio 1995 a julio 1997 se evaluó la prevalencia de CA, en 50 pacientes diabéticos y 11 no diabéticos. A todos se le realizaron las pruebas de los reflejos cardiovasculares normalizados por Ewing. Se usó para el análisis estadístico el test de t de Student para muestras no pareadas. Se consideró estadísticamente significativo a los valores con un p<0.05. Resultados: En el grupo control las pruebas presentaron valores normales; la variación de la frecuencia cardíaca durante la respiración profunda (RP) fue X 18,6 ñ 0.95; la Maniobra de Valsalva(V) X 1.1 ñ 0.05; la prueba de pararse(S) X 1.19 ñ 0.02 y variación de la presión arterial al pararse(PA): X 10 ñ 2. En los diabéticos, la RP mostro 70 por ciento de resultados patológicos con una X 3.6 ñ 0.9 latidos por minuto. En V se evaluaron 34 pacientes resultando patológico en el 59 por ciento de los casos con una X 0.9 ñ 0.2. En S observamos 67 por ciento de resultados patológicos con una X 0.9 ñ 0.06 y la PA : delta X 17.7 ñ 4.6. Conclusión: se detectó alta prevalencia de neuropatía autonómica cardíaca en diabéticos. Con una diferencia significativa (p<0.01) para las cuatro pruebas.

Disfunción autonómica cardíaca en diabetes mellitus / Autonomic cardiac dysfunction at Diabetes Mellitus

Objetivo: Evaluar la prevalencia de cardiopatía autonómica (CA) en pacientes con Diabetes Mellitus asistidos en consultorio externo. Material y Método: Desde julio 1995 a julio 1997 se evaluó la prevalencia de CA, en 50 pacientes diabéticos y 11 no diabéticos. A todos se le realizaron las pruebas de los reflejos cardiovasculares normalizados por Ewing. Se usó para el análisis estadístico el test de t de Student para muestras no pareadas. Se consideró estadísticamente significativo a los valores con un p<0.05. Resultados: En el grupo control las pruebas presentaron valores normales; la variación de la frecuencia cardíaca durante la respiración profunda (RP) fue X 18,6 ñ 0.95; la Maniobra de Valsalva(V) X 1.1 ñ 0.05; la prueba de pararse(S) X 1.19 ñ 0.02 y variación de la presión arterial al pararse(PA): X 10 ñ 2. En los diabéticos, la RP mostro 70 por ciento de resultados patológicos con una X 3.6 ñ 0.9 latidos por minuto. En V se evaluaron 34 pacientes resultando patológico en el 59 por ciento de los casos con una X 0.9 ñ 0.2. En S observamos 67 por ciento de resultados patológicos con una X 0.9 ñ 0.06 y la PA : delta X 17.7 ñ 4.6. Conclusión: se detectó alta prevalencia de neuropatía autonómica cardíaca en diabéticos. Con una diferencia significativa (p<0.01) para las cuatro pruebas. (AU)