Ultra rapid in vivo screening for anti-Alzheimer anti-amyloid drugs

More than 46 million people worldwide suffer from Alzheimer's disease. A large number of potential treatments have been proposed; among these, the inhibition of the aggregation of amyloid β-peptide (Aβ), considered one of the main culprits in Alzheimer's disease. Limitations in monitoring the aggregation of Aβ in cells and tissues restrict the screening of anti-amyloid drugs to in vitro studies in most cases. We have developed a simple but powerful method to track Aβ aggregation in vivo in realtime, using bacteria as in vivo amyloid reservoir. We use the specific amyloid dye Thioflavin-S (Th-S) to stain bacterial inclusion bodies (IBs), in this case mainly formed of Aβ in amyloid conformation. Th-S binding to amyloids leads to an increment of fluorescence that can be monitored. The quantification of the Th-S fluorescence along the time allows tracking Aβ aggregation and the effect of potential antiaggregating agents

Necrotizing Sarcoid Granulomatosis: A Disease Not to be Forgotten

Sarcoidosis is a systemic granulomatous disease of unknown aetiology characterised by the appearance of noncaseifying epithelioid granulomas in the affected organs, most commonly the lungs, skin, and eyes (Iannuzzi et al. 2007). Necrotizing Sarcoid Granulomatosis (NGS) is a rare and little-known form of disease, which also presents nodular lung lesions, and it shares pathologic and clinical findings with sarcoidosis, where the presence of necrosis may lead to misdiagnosis of tuberculosis (TB), leading to a consequent delay in treatment of the underlying entity (Chong et al. 2015). ,is is exactly what happened with the two cases that we present here

Clinical factors associated with high glycemic variability defined by coefficient of variation in patients with type 2 diabetes

Antecedentes: La Variabilidad Glucémica Alta (VHG) ha convertirse en un predictor más fuerte de hipoglucemia. Sin embargo, aún se desconocen los factores clínicos asociados con el VHG. Objetivo:Determinar las variables clínicas que se asociaron con un coeficiente de variación (CV) superior al 36% evaluado mediante monitorización continua de glucosa (MCG) en un grupo de pacientes con diabetes mellitus. Métodos: Se evaluó una cohorte de pacientes con diabetes tipo 2 (T2D). Se evaluaron variables demográficas, HbA1c, tasa de filtración glomerular (TFG) y régimen de tratamiento. Se realizó un análisis bivariado, para evaluar la asociación entre la variable resultado (CV > 36%) y cada una de las variables independientes. Se construyó un modelo multivariado para evaluar las asociaciones después de controlar las variables de confusión. Resultados:Se analizaron los datos de MCG de 274 pacientes. CV> 36% estuvo presente en 56 pacientes (20,4%). En el análisis bivariado se incluyeron variables demográficas y clínicas, como tiempo desde el diagnóstico, antecedente de hipoglucemia, A1c, FG y tratamiento instaurado. En el análisis multivariante, FG 9% (OR 2,81; IC 1,05,7,51; p:0,04) y antecedentes de hipoglucemia (OR 2,09; IC 1,02, 4,32; p: 0,04) se asociaron con VHG. El tratamiento con iDPP4 (OR 0,39; IC 0,19, 0,82; p: 0,01) y AGLP1 (OR 0,08; IC 0,01, 0,68; p: 0,02) se asoció inversamente con la VG. Conclusión:Variables clínicas como FG 9% y antecedentes de hipoglucemia se asocian a un VG alto. Nuestros datos sugieren que el uso de tecnología y tratamientos capaces de reducir la variabilidad glucémica podría ser útil en esta población para reducir el riesgo de hipoglucemia y mejorar el control glucémico.Q3Background: High glycemic Variability (HGV) has become a stronger predictor of hypoglycemia. However, clinical factors associate with HGV still are unknown. Objective: To determine clinical variables that were associated with a coefficient of variation (CV) above 36% evaluated by continuous glucose monitoring (CGM) in a group of patients with diabetes mellitus. Methods: A cohort of patients with type 2 diabetes (T2D) was evaluated. Demographic variables, HbA1c, glomerular filtration rate (GFR) and treatment regimen were assessed. A bivariate analysis was performed, to evaluate the association between the outcome variable (CV> 36%) and each of the independent variables. A multivariate model was constructed to evaluate associations after controlling for confounding variables. Results: CGM data from 274 patients were analyzed. CV> 36% was present in 56 patients (20.4%). In the bivariate analysis, demographic and clinical variables were included, such as time since diagnosis, hypoglycemia history, A1c, GFR and treatment established. In the multivariate analysis, GFR 9% (OR 2.81; CI 1.05,7.51; p:0.04) and hypoglycemia history (OR 2.09; CI 1.02,4.32; p:0.04) were associated with HGV. Treatment with iDPP4 (OR 0.39; CI 0.19,0.82; p:0.01) and AGLP1 (OR 0.08; CI 0.01,0.68; p:0.02) was inversely associated with GV. Conclusion: Clinical variables such as GFR 9% and a history of hypoglycemia are associated with a high GV. Our data suggest that the use of technology and treatments able to reduce glycemic variability could be useful in this population to reduce the risk of hypoglycemia and to improve glycemic control.Revista Internacional - Indexad

Efecto de dosis y época de aplicación de nitrógeno e inoculación con Rhizobium en el rendimiento de la soya en la meseta de Ibagué.

La aplicación de N se hizo en 3 períodos: la salida de la primera hoja, al comienzo de la floración y a la formación de las vainas. Las dosis de N utilizadas fueron 0, 25, 50, 75, 100, 125, 175 y 200 kg/ha. Cada tratamiento recibió Rhizobium japonicum de la raza CIAT-45, a excepción del control. El N fué aplicado como úrea directamente al surco. Se observaron efectos significativos del nivel de N en el rendimiento de semillas, número de vaínas, altura de planta, altura de la primera vaina, y número de nodulos en la raíz. El más alto rendimiento se obtuvo con 75 y 100 kg/ha de N. Estos tratamientos incrementaron el rendimiento en un 49 por ciento comparado con el control. El número de nódulos se aumentó hasta con aplicaciones de 75 kg/ha. Más allá de este nivel no se incrementó el número de nódulosSoya-Soja- Glycine ma

Producción de antisuero contra el virus X de la papa (Solanum tuberosum L.)y su incorporación a los servicios de detección mediante ELISA

Se purificó el virus X de la papa a partir de Nicotiana glutinosa L., clarificando el jugo vegetal por medio de ciclos de centrifugación a baja velocidad, precipitación con polietilenglicol , colchón de sacarosa y ultracentrifugación en gradiente de densidad de sacarosa. Con los purificados se inmunizaron conejos obteniéndose un antisuero con título 1/128 en pruebas de micro precipitación . Se purificó la gammaglobulina, parte de la cual fue conjugada con fosfatasa alcalina para utilizarla en pruebas ELISA. La gamaglobulina y conjugados obtenidos han sido incorporados al servicio de detección de virus de papa

Immune response to SARS-CoV-2 variants after immunization with different vaccines in Mexico

There is limited information on the antibody responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in subjects from developing countries with populations having a high incidence of co-morbidities. Here, we analysed the immunogenicity of homologous schemes using the ChAdOx1-S, Sputnik V, or BNT162b2 vaccines and the effect of a booster dose with ChAdOx1-S in middle-aged adults who were seropositive or seronegative to the SARS-CoV-2 spike protein before vaccination. The study was conducted post-vaccination with a follow-up of 4 months for antibody titre using enzyme-linked immunosorbent assay (ELISA) and pseudovirus (PV) neutralization assays (PNAs). All three vaccines elicited a superior IgG anti-receptor-binding domain (RBD) and neutralization response against the Alpha and Delta variants when administered to individuals with a previous infection by SARS-CoV-2. The booster dose spiked the neutralization activity among individuals with and without a prior SARS-CoV-2 infection. The ChAdOx1-S vaccine induced weaker antibody responses in infection-naive subjects. A follow-up of 4 months post-vaccination showed a drop in antibody titre, with about 20% of the infection-naive and 100% of SARS-CoV-2 pre-exposed participants with detectable neutralization capacity against Alpha pseudovirus (Alpha-PV) and Delta PV (Delta-PV). Our observations support the use of different vaccines in a country with high seroprevalence at the vaccination time

Prevalencia de dolor crónico en una población rural de Guatemala

El objetivo fue determinar la prevalencia de dolor crónico en una población adulta del área norte micro-región III, Salamá, Baja Verapaz, Guatemala, durante abril-mayo 2017. El estudio fue descriptivo, transversal por muestreo bietápico, estudiando 243 viviendas y 367 personas de la etnia achí, que se encuestaron según la escala de gradación del dolor modificada, avalada por la Sociedad Española de Reumatología. Ésta evaluó la prevalencia del dolor, características sociodemográficas, promedio de días con dolor, intensidad y discapacidad, localización y comorbilidades asociadas. Se obtuvo un consentimiento informado y aval del Comité de Bioética en Investigación de Salud de la Facultad de Ciencias Médicas, Usac. Se usó estadística descriptiva, frecuencias y porcentajes para variables categóricas y medidas de tendencia central y dispersión para variables numéricas. La prevalencia de dolor crónico fue 9.12% (211), edad media 41 ± 16 años y 82.9% (175) de sexo femenino. El promedio de días de dolor fue de 74 días en los últimos tres meses. En el 54.03% (114) el dolor fue de intensidad severa, con discapacidad leve en 67.78% (97). La cabeza, rodillas y columna lumbar fueron las localizaciones más frecuentes. Las comorbilidades predominantes fueron hipertensión arterial, gastritis y cefalea. Se determinó que la prevalencia del dolor crónico en una población rural del municipio de Salamá es de 9.12%, con intensidad severa en la mitad y discapacidad leve en 7 de cada 10 habitantes

Joint source and relay design for MIMO multi-relay systems using projected gradient approach

In this paper, we develop the optimal source precoding matrix and relay amplifying matrices for non-regenerative multiple-input multiple-output (MIMO) relay communication systems with parallel relay nodes using the projected gradient (PG) approach. We show that the optimal relay amplifying matrices have a beamforming structure. Exploiting the structure of relay matrices, an iterative joint source and relay matrices optimization algorithm is developed to minimize the mean-squared error (MSE) of the signal waveform estimation at the destination using the PG approach. The performance of the proposed algorithm is demonstrated through numerical simulations

Six More Ultra-Faint Milky Way Companions Discovered in the DECam Local Volume Exploration Survey

We report the discovery of six ultra-faint Milky Way satellites discovered through matched-filter searches conducted using Dark Energy Camera (DECam) data processed as part of the second data release of the DECam Local Volume Exploration (DELVE) survey. Leveraging deep Gemini/GMOS-N imaging (for four candidates) as well as follow-up DECam imaging (for two candidates), we characterize the morphologies and stellar populations of these systems. We find that these candidates all share faint absolute magnitudes ($M_{V} \geq -3.2$ mag) and old, metal-poor stellar populations ($\tau > 10$ Gyr, [Fe/H] $< -1.4$ dex). Three of these systems are more extended ($r_{1/2} > 15$ pc), while the other three are compact ($r_{1/2} < 10$ pc). From these properties, we infer that the former three systems (Bo\"{o}tes V, Leo Minor I, and Virgo II) are consistent with ultra-faint dwarf galaxy classifications, whereas the latter three (DELVE 3, DELVE 4, and DELVE 5) are likely ultra-faint star clusters. Using data from the Gaia satellite, we confidently measure the proper motion of Bo\"{o}tes V, Leo Minor I, and DELVE 4, and tentatively detect a proper motion signal from DELVE 3 and DELVE 5; no signal is detected for Virgo II. We use these measurements to explore possible associations between the newly-discovered systems and the Sagittarius dwarf spheroidal, the Magellanic Clouds, and the Vast Polar Structure, finding several plausible associations. Our results offer a preview of the numerous ultra-faint stellar systems that will soon be discovered by the Vera C. Rubin Observatory and highlight the challenges of classifying the faintest stellar systems.Comment: 30 pages, 12 Figures (including Appendix). Submitted to ApJ. We encourage the reader to also review Smith et al. 2022, "Discovery of a new Local Group Dwarf Galaxy Candidate in UNIONS: Bo\"{o}tes V" (arxiv: 2209.08242), who independently present the discovery of one of the candidates reported here. We are working to make code and data products availabl

Anti-Inflammatory Effects of Resveratrol, Curcumin and Simvastatin in Acute Small Intestinal Inflammation

BACKGROUND: The health beneficial effects of Resveratrol, Curcumin and Simvastatin have been demonstrated in various experimental models of inflammation. We investigated the potential anti-inflammatory and immunomodulatory mechanisms of the above mentioned compounds in a murine model of hyper-acute Th1-type ileitis following peroral infection with Toxoplasma gondii. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that after peroral administration of Resveratrol, Curcumin or Simvastatin, mice were protected from ileitis development and survived the acute phase of inflammation whereas all Placebo treated controls died. In particular, Resveratrol treatment resulted in longer-term survival. Resveratrol, Curcumin or Simvastatin treated animals displayed significantly increased numbers of regulatory T cells and augmented intestinal epithelial cell proliferation/regeneration in the ileum mucosa compared to placebo control animals. In contrast, mucosal T lymphocyte and neutrophilic granulocyte numbers in treated mice were reduced. In addition, levels of the anti-inflammatory cytokine IL-10 in ileum, mesenteric lymph nodes and spleen were increased whereas pro-inflammatory cytokine expression (IL-23p19, IFN-γ, TNF-α, IL-6, MCP-1) was found to be significantly lower in the ileum of treated animals as compared to Placebo controls. Furthermore, treated animals displayed not only fewer pro-inflammatory enterobacteria and enterococci but also higher anti-inflammatory lactobacilli and bifidobacteria loads. Most importantly, treatment with all three compounds preserved intestinal barrier functions as indicated by reduced bacterial translocation rates into spleen, liver, kidney and blood. CONCLUSION/SIGNIFICANCE: Oral treatment with Resveratrol, Curcumin or Simvastatin ameliorates acute small intestinal inflammation by down-regulating Th1-type immune responses and prevents bacterial translocation by maintaining gut barrier function. These findings provide novel and potential prophylaxis and treatment options of patients with inflammatory bowel diseases