Evaluacíon de la actividad biológica in vitro de factores extracelulares de Lactobacillus acidophilus y Bifidobacterium longum sobre línea celular HT-29 de cáncer de colon humano.

Los probióticos son organismos vivos que cuando se administran en cantidades adecuadas ejercen un efecto benéfico para la salud del huésped. Se ha demostrado que varias cepas probióticas ejercen efectos benéficos tanto en la microbiota endógena como en el epitelio y el sistema inmune intestinal. Como microorganismos probióticos se utilizan los géneros Lactobacillus y Bifidobacterium. Hay datos que indican que los probióticos pueden impedir o retrasar la aparición de ciertos tipos de cáncer. Varios trabajos in vivo e in vitro han demostrado que probióticos detoxifican y tienen propiedad antimutagénica. Se ha demostrado en algunos trabajos in vitro que los factores extracelulares han presentado actividad biológica sobre protozoarios y bacterias de importancia médica, es por esto que en este trabajo se obtuvieron factores extracelulares de Lactobacillus acidophilus y Bifidobacterium longum para determinar la actividad biológica sobre la línea tumoral HT-29. Con los factores extracelulares, a diferentes dosis, se observó una marcada inhibición del crecimiento de HT-29, siendo las mejores concentraciones las de 13mg/mL y 26mg/mL. Se concluye que los factores extracelulares si inhiben el crecimiento de HT-29 y esto puede generar más experimentos in vitro e in vivo para demostrar la actividad antagonista de probióticos en células de cáncer

ACTIVIDAD AMEBICIDA, ANTIOXIDANTE Y PERFIL FITOQUÍMICO DE EXTRACTOS METANÓLICOS DE ASTROPHYTUM MYRIOSTIGMA OBTENIDOS DE CULTIVO DE CALLO Y DEL CACTUS SILVESTRE

Methanolic extracts were obtained fromboth in vitro and ex vitro tissues of Astrophytum myriostigma to develop a phytochemical profile, probe antioxidant activity(DPPH 2, 2-diphenyl-1-picryl-hydrazyl)and evaluate amoebicid activity againstEntamoeba histolytica HM1-IMSS. Thephytochemical profile results indicate thepresence of different secondary metabolitesin callus and stem; whereas the callus hasphenolic oxidrils and flavonoids, these arenot present in the stem, which may causethe difference in the antioxidant activitybetween callus with an IC50 of 199.19μg/mL and stem with 3961.39 μg/mL. Theamoebicid activity was satisfactory withan IC50 of <100μg/mL for both extracts.The presence of these metabolites in callusof Astrophytum myriostigma is probablydue to conditions and nutrients present inmedia.Se determinó la actividad amebicida, antioxidante y perfil fitoquímico de extractosmetanólicos de callo cultivado in vitro ysecciones de tallo de planta ex vitro deAstrophytum myriostigma. Se obtuvieronextractos metanólicos de ambos tejidos paraevaluar la actividad amebicida sobre Entamoeba histolytica HM1-IMSS, la actividadantioxidante (DPPH 2,2-diphenyl-1-picrylhydrazyl) y su perfil fitoquímico. Paraambos extractos, la actividad amebicidaresultó satisfactoria con una concentracióninhibitoria media menor de 100 μg/mL. Losresultados del perfil fitoquímico indican lapresencia de metabolitos secundarios diferentes en callo y tallo, mientras que el callo,posee oxidrilos fenólicos y flavonoides,en tallo no están presentes, lo que puedeocasionar la diferencia en los resultadosde la actividad antioxidante, para callo unaconcentración efectiva media de 199.19μg/mL y para tallo de 3961.39 μg/mL. Lapresencia de estos metabolitos en callo deAstrophytum myriostigma, se debe probablemente a las condiciones y a los nutrientespresentes en el medio in vitro

Use of Tirzepatide in adults with type 2 diabetes mellitus: scientifc evidence and practical aspects

Tirzepatide is a novel antidiabetic medication a single-molecule, agonist to the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors. It is approved in the USA and EU for the treatment of type 2 diabetes mellitus (T2DM) and obesity. Due to the potential novelty represented by incorporating tirzepatide to clinical practice, we aim to review practical aspects of tirzepatide use in T2DM and the supporting scientific evidence. A group of ten endocrinologists involved as investigators in the phase 3 SURPASS clinical trial program followed a nominal group technique, a qualitative research methodology designed as a semi-structured group discussion to reach a consensus on the selection of a set of practical aspects. The scientific evidence for tirzepatide has been reviewed with respect to a number of patients' clinical profiles and care goals. Information of interest related to adverse events, special warnings and precautions, and other considerations for tirzepatide use has been included. Finally, information provided to the patients has been summarized. The practical aspects reported herein may be helpful in guiding physicians in the use of tirzepatide and contribute to optimizing the management of T2DM.Funding. This work and the Rapid Service Fee was sponsored by Eli Lilly and Company

BIOPROSPECCIÓN DE LA ACTIVIDAD ANTIMICÓTICA DE EXTRACTOS METANÓLICOS DE ARIOCARPUS KOTSCHOUBEYANUS Y ARIOCARPUS RETUSUS

The antifungal activity of methanolic extracts from Ariocarpus kotschoubeyanusand A. retusus, two native xerophytes ofnortheastern Mexico, was determined onthe fungal dermatophytes Trichophytontonsurans, Microsporum canis and Microsporum cookei. Putative active metabolites were identified by phytochemicalscreening using evidence for functionalgroups; determination of antifungal activity was conducted by the disk-diffusion platemethod as part of the process of understanding the chemistry and efficacy of theseplant products. Doses tested were 125,250 y 500 mg/mL. Extracts were positivefor carbonyl groups, phenolic oxhidrils,sterols and methyl sterols, coumarins, sesquiterpenlactones, saponins, flavonoids andalkaloids. Extract from A. retusus (stem)yielded the greatest activity against Trichophyton tonsurans and Microsporum cookei.Univariate analysis of variance revealedthat with regard to antifungal activity therewere significant differences between fungi,culture media and analyzed doses withrespect to positive control of ketoconazole.These results served to validate empiricalknowledge about these plants in traditionalmedicine. These studies form a basis forfurther research in the search for bioactivecompounds and the discovery of potentialherbal medicaments.Se determinó la actividad antifúngica invitro de extractos metanólicos de Ariocarpus kotschoubeyanus y Ariocarpusretusus, plantas xerófitas del noreste delpaís, usadas en la medicina tradicional,sobre los hongos dermatofitos Trichophytontonsurans, Microsporum canis y Microsporum cookei. Los metabolitos presentes seidentificaron por tamizaje fitoquímico empleando pruebas para grupos funcionales, ladeterminación de actividad antifúngica serealizó por el método de difusión en placaempleando microdiscos, con la finalidadde entender la química y eficacia de estosproductos vegetales, las dosis evaluadasde estos extractos fueron 125, 250 y 500mg/mL. Los extractos resultaron positivospara grupos carbonilo, oxidrilos fenólicos,esteroles y metilesteroles, cumarinas, sesquiterpenlactonas, saponinas, flavonoides yalcaloides. El extracto que presentó mayoractividad fue el de Ariocarpus retusus(tallo) contra Trichophyton tonsurans y Microsporum cookei. El análisis estadístico devarianza univariante reveló que en cuantoa la actividad antifúngica, existe diferencia significativa entre hongos, medios de cultivo y dosis evaluadas de los extractos conrespecto al control positivo de ketoconazol.Estos resultados sirvieron para validar elconocimiento empírico que se tiene acercade estas plantas en la medicina tradicional.Siendo estos estudios una base para nuevas investigaciones sobre la búsqueda decompuestos bioactivos y el descubrimientode medicamentos potenciales de productosherbales

Design and baseline characteristics of SALT‐HF trial: hypertonic saline therapy in ambulatory heart failure

Aims Hypertonic saline solution (HSS) plus intravenous (IV) loop diuretic appears to enhance the diuretic response in patients hospitalized for heart failure (HF). The efficacy and safety of this therapy in the ambulatory setting have not been evaluated. We aimed to describe the design and baseline characteristics of the SALT-HF trial participants. Methods and results 'Efficacy of Saline Hypertonic Therapy in Ambulatory Patients with HF' (SALT-HF) trial was a multicenter, double-blinded, and randomized study involving ambulatory patients who experienced worsening heart failure (WHF) without criteria for hospitalization. Enrolled patients had to present at least two signs of volume overload, use >= 80 mg of oral furosemide daily, and have elevated natriuretic peptides. Patients were randomized 1:1 to treatment with a 1-h infusion of IV furosemide plus HSS (2.6-3.4% NaCl depending on plasmatic sodium levels) versus a 1-h infusion of IV furosemide at the same dose (125-250 mg, depending on basal loop diuretic dose). Clinical, laboratory, and imaging parameters were collected at baseline and after 7 days, and a telephone visit was planned after 30 days. The primary endpoint was 3-h diuresis after treatment started. Secondary endpoints included (a) 7-day changes in congestion data, (b) 7-day changes in kidney function and electrolytes, (c) 30-day clinical events (need of IV diuretic, HF hospitalization, cardiovascular mortality, all-cause mortality or HF-hospitalization). Results A total of 167 participants [median age, 81 years; interquartile range (IQR), 73-87, 30.5% females] were randomized across 13 sites between December 2020 and March 2023. Half of the participants (n = 82) had an ejection fraction >50%. Most patients showed a high burden of comorbidities, with a median Charlson index of 3 (IQR: 2-4). Common co-morbidities included diabetes mellitus (41%, n = 69), atrial fibrillation (80%, n = 134), and chronic kidney disease (64%, n = 107). Patients exhibited a poor functional NYHA class (69% presenting NYHA III) and several signs of congestion. The mean composite congestion score was 4.3 (standard deviation: 1.7). Ninety per cent of the patients (n = 151) presented oedema and jugular engorgement, and 71% (n = 118) showed lung B lines assessed by ultrasound. Median inferior vena cava diameter was 23 mm, (IQR: 21-25), and plasmatic levels of N-terminal-pro-B-type natriuretic peptide (NTproBNP) and antigen carbohydrate 125 (CA125) were increased (median NT-proBNP 4969 pg/mL, IQR: 2508-9328; median CA125 46 U/L, IQR: 20-114). Conclusions SALT-HF trial randomized 167 ambulatory patients with WHF and will determine whether an infusion of hypertonic saline therapy plus furosemide increases diuresis and improves decongestion compared to equivalent furosemide administration alone

Design and baseline characteristics of SALT-HF trial: hypertonic saline therapy in ambulatory heart failure

Aims: Hypertonic saline solution (HSS) plus intravenous (IV) loop diuretic appears to enhance the diuretic response in patients hospitalized for heart failure (HF). The efficacy and safety of this therapy in the ambulatory setting have not been evaluated. We aimed to describe the design and baseline characteristics of the SALT-HF trial participants. Methods and results: ‘Efficacy of Saline Hypertonic Therapy in Ambulatory Patients with HF’ (SALT-HF) trial was a multicenter, double-blinded, and randomized study involving ambulatory patients who experienced worsening heart failure (WHF) without criteria for hospitalization. Enrolled patients had to present at least two signs of volume overload, use ≥ 80 mg of oral furosemide daily, and have elevated natriuretic peptides. Patients were randomized 1:1 to treatment with a 1-h infusion of IV furosemide plus HSS (2.6–3.4% NaCl depending on plasmatic sodium levels) versus a 1-h infusion of IV furosemide at the same dose (125–250 mg, depending on basal loop diuretic dose). Clinical, laboratory, and imaging parameters were collected at baseline and after 7 days, and a telephone visit was planned after 30 days. The primary endpoint was 3-h diuresis after treatment started. Secondary endpoints included (a) 7-day changes in congestion data, (b) 7-day changes in kidney function and electrolytes, (c) 30-day clinical events (need of IV diuretic, HF hospitalization, cardiovascular mortality, all-cause mortality or HF-hospitalization). Results: A total of 167 participants [median age, 81 years; interquartile range (IQR), 73–87, 30.5% females] were randomized across 13 sites between December 2020 and March 2023. Half of the participants (n = 82) had an ejection fraction >50%. Most patients showed a high burden of comorbidities, with a median Charlson index of 3 (IQR: 2–4). Common co-morbidities included diabetes mellitus (41%, n = 69), atrial fibrillation (80%, n = 134), and chronic kidney disease (64%, n = 107). Patients exhibited a poor functional NYHA class (69% presenting NYHA III) and several signs of congestion. The mean composite congestion score was 4.3 (standard deviation: 1.7). Ninety per cent of the patients (n = 151) presented oedema and jugular engorgement, and 71% (n = 118) showed lung B lines assessed by ultrasound. Median inferior vena cava diameter was 23 mm, (IQR: 21–25), and plasmatic levels of N-terminal-pro-B-type natriuretic peptide (NTproBNP) and antigen carbohydrate 125 (CA125) were increased (median NT-proBNP 4969 pg/mL, IQR: 2508–9328; median CA125 46 U/L, IQR: 20–114). Conclusions: SALT-HF trial randomized 167 ambulatory patients with WHF and will determine whether an infusion of hypertonic saline therapy plus furosemide increases diuresis and improves decongestion compared to equivalent furosemide administration alone

Neutrophil count is associated with reduced gray matter and enlarged ventricles in first-episode psychosis

Although there is recent evidence that cells from the peripheral immune system can gain access to the central nervous system in certain conditions such as multiple sclerosis, their role has not been assessed in psychosis. Here, we aimed to explore whether blood cell count was associated with brain volume and/or clinical symptomatology. A total of 218 participants (137 first-episode psychosis patients [FEP] and 81 healthy controls [HC]) were included in the study. For each participant, a T1 structural image was acquired, from which brain tissue volumes were calculated. We found that, in FEP, neutrophil count was associated with reduced gray matter (GM) volume (ß = -0.117, P < .001) and increased cerebrospinal fluid volume (ß = 0.191, P = .007). No associations were observed in HC. GM reduction was generalized but more prominent in certain regions, notably the thalamus, the anterior insula, and the left Heschl''s gyrus, among many others. Neutrophil count was also associated with the total PANSS score (ß = 0.173, P = .038), including those items assessing hallucinations (ß = 0.182, P = .028) and avolition (ß = 0.197, P = .018). Several confounders, such as antipsychotic medication, body mass index, and smoking, were controlled for. Overall, the present study may represent the first indirect evidence of brain tissue loss associated with neutrophils in psychosis, and lends support to the hypothesis of a dysregulated immune system. Higher neutrophil count was also associated with more severe clinical symptomatology, which renders it a promising indicator of schizophrenia severity and could even give rise to new therapies

The Imaging Magnetograph eXperiment (IMaX) for the Sunrise balloon-borne solar observatory

The Imaging Magnetograph eXperiment (IMaX) is a spectropolarimeter built by four institutions in Spain that flew on board the Sunrise balloon-borne telesocope in June 2009 for almost six days over the Arctic Circle. As a polarimeter IMaX uses fast polarization modulation (based on the use of two liquid crystal retarders), real-time image accumulation, and dual beam polarimetry to reach polarization sensitivities of 0.1%. As a spectrograph, the instrument uses a LiNbO3 etalon in double pass and a narrow band pre-filter to achieve a spectral resolution of 85 mAA. IMaX uses the high Zeeman sensitive line of Fe I at 5250.2 AA and observes all four Stokes parameters at various points inside the spectral line. This allows vector magnetograms, Dopplergrams, and intensity frames to be produced that, after reconstruction, reach spatial resolutions in the 0.15-0.18 arcsec range over a 50x50 arcsec FOV. Time cadences vary between ten and 33 seconds, although the shortest one only includes longitudinal polarimetry. The spectral line is sampled in various ways depending on the applied observing mode, from just two points inside the line to 11 of them. All observing modes include one extra wavelength point in the nearby continuum. Gauss equivalent sensitivities are four Gauss for longitudinal fields and 80 Gauss for transverse fields per wavelength sample. The LOS velocities are estimated with statistical errors of the order of 5-40 m/s. The design, calibration and integration phases of the instrument, together with the implemented data reduction scheme are described in some detail.Comment: 17 figure

Multi-particle azimuthal correlations in p-Pb and Pb-Pb collisions at the CERN Large Hadron Collider

Measurements of multi-particle azimuthal correlations (cumulants) for charged particles in p-Pb and Pb-Pb collisions are presented. They help address the question of whether there is evidence for global, flow-like, azimuthal correlations in the p-Pb system. Comparisons are made to measurements from the larger Pb-Pb system, where such evidence is established. In particular, the second harmonic two-particle cumulants are found to decrease with multiplicity, characteristic of a dominance of few-particle correlations in p-Pb collisions. However, when a $|\Delta \eta|$ gap is placed to suppress such correlations, the two-particle cumulants begin to rise at high-multiplicity, indicating the presence of global azimuthal correlations. The Pb-Pb values are higher than the p-Pb values at similar multiplicities. In both systems, the second harmonic four-particle cumulants exhibit a transition from positive to negative values when the multiplicity increases. The negative values allow for a measurement of $v_{2}\{4\}$ to be made, which is found to be higher in Pb-Pb collisions at similar multiplicities. The second harmonic six-particle cumulants are also found to be higher in Pb-Pb collisions. In Pb-Pb collisions, we generally find $v_{2}\{4\} \simeq v_{2}\{6\}\neq 0$ which is indicative of a Bessel-Gaussian function for the $v_{2}$ distribution. For very high-multiplicity Pb-Pb collisions, we observe that the four- and six-particle cumulants become consistent with 0. Finally, third harmonic two-particle cumulants in p-Pb and Pb-Pb are measured. These are found to be similar for overlapping multiplicities, when a $|\Delta\eta| > 1.4$ gap is placed.Comment: 25 pages, 11 captioned figures, 3 tables, authors from page 20, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/87