Streptococcus agalactiae infection in zebrafish larvae.

Streptococcus agalactiae (Group B Streptococcus, GBS) is an encapsulated, Gram-positive bacterium that is a leading cause of neonatal pneumonia, sepsis and meningitis, and an emerging aquaculture pathogen. The zebrafish (Danio rerio) is a genetically tractable model vertebrate that has been used to analyze the pathogenesis of both aquatic and human bacterial pathogens. We have developed a larval zebrafish model of GBS infection to study bacterial and host factors that contribute to disease progression. GBS infection resulted in dose dependent larval death, and GBS serotype III, ST-17 strain was observed as the most virulent. Virulence was dependent on the presence of the GBS capsule, surface anchored lipoteichoic acid (LTA) and toxin production, as infection with GBS mutants lacking these factors resulted in little to no mortality. Additionally, interleukin-1ß (il1b) and CXCL-8 (cxcl8a) were significantly induced following GBS infection compared to controls. We also visualized GBS outside the brain vasculature, suggesting GBS penetration into the brain during the course of infection. Our data demonstrate that zebrafish larvae are a valuable model organism to study GBS pathogenesis.

Human Tumor-Associated Macrophages and Neutrophils Regulate Antitumor Antibody Efficacy through Lethal and Sublethal Trogocytosis.

The clinical benefits of tumor-targeting antibodies (tAb) are modest in solid human tumors. The efficacy of many tAbs is dependent on Fc receptor (FcR)-expressing leukocytes that bind Fc fragments of tAb. Tumor-associated macrophages (TAM) and neutrophils (TAN) represent the majority of FcR+ effectors in solid tumors. A better understanding of the mechanisms by which TAMs and TANs regulate tAb response could help improve the efficacy of cancer treatments. Here, we found that myeloid effectors interacting with tAb-opsonized lung cancer cells used antibody-dependent trogocytosis (ADT) but not antibody-dependent phagocytosis. During this process, myeloid cells "nibbled off" tumor cell fragments containing tAb/targeted antigen (tAg) complexes. ADT was only tumoricidal when the tumor cells expressed high levels of tAg and the effectors were present at high effector-to-tumor ratios. If either of these conditions were not met, which is typical for solid tumors, ADT was sublethal. Sublethal ADT, mainly mediated by CD32hiCD64hi TAM, led to two outcomes: (i) removal of surface tAg/tAb complexes from the tumor that facilitated tumor cell escape from the tumoricidal effects of tAb; and (ii) acquisition of bystander tAgs by TAM with subsequent cross-presentation and stimulation of tumor-specific T-cell responses. CD89hiCD32loCD64lo peripheral blood neutrophils (PBN) and TAN stimulated tumor cell growth in the presence of the IgG1 anti-EGFR Ab cetuximab; however, IgA anti-EGFR Abs triggered the tumoricidal activity of PBN and negated the stimulatory effect of TAN. Overall, this study provides insights into the mechanisms by which myeloid effectors mediate tumor cell killing or resistance during tAb therapy. SIGNIFICANCE: The elucidation of the conditions and mechanisms by which human FcR+ myeloid effectors mediate cancer cell resistance and killing during antibody treatment could help develop improved strategies for treating solid tumors.

From purposeless residues to biocomposites: A hyphae made connection.

Biocomposites create attractive alternatives to match packing needs with available agricultural residues. Growing native fungal strains developed a mycelium biocomposite over a mixture of Peach Palm Fruit Peel Flour and Sugar Cane Bagasse Wet Dust. A methodology was proposed to analyze their main characteristics: 1) morphological, 2) chemical, and 3) biodegradability. 1) SEM analysis evidenced the structural change of the dried vs pressed material and mycelium morphology for both species. 2) The ratio lignin:carbohydrate showed that P. ostreatus degrades the cellulose-hemicellulose fraction of the substrate at a higher rate than T. elegans, and 3) the curve BMP indicated that these materials are readily biodegradable with a maximum yield of 362,50 mL biogas/g VS. An innovative tangible valorization strategy based on mass balances is also presented: from just 50 kg of peel flour, up to 1840 units can be manufactured, which could pave the way for a more sustainable future.

Engaging Scientific Diasporas in STEAM Education: The Case of Science Clubs Colombia.

Currently, there is limited insight on the role that scientific diasporas can play in STEAM education in Latin America. Here, we present the Science Clubs Colombia (Clubes de Ciencia Colombia-SCC) program, a pioneering STEAM capacity-building initiative led by volunteer scientists to engage youth and children from underserved communities in science. The program brings together researchers based in Colombia and abroad to lead intensive project-based learning workshops for young students in urban and rural areas. These projects focus on channeling the students' technical and cognitive scientific aptitudes to tackle challenges of both local and global relevance. The program provides high-quality STEAM education adapted to communities' needs and articulates long-lasting international collaborations using the mobility of the Colombian diaspora. The program's success is tangible via its sustained growth and adaptability. Since its first version in 2015, 722 volunteer scientists living abroad or in Colombia have collaborated to create 364 clubs with the participation of 9,295 students. We describe elements of the SCC program that lead to a scalable and reproducible outcome to engage science diasporas in STEAM education. Additionally, we discuss the involvement of multiple stakeholders and the generation of international networks as potential science diplomacy outcomes. The SCC program strengthens the involvement of Latin American youth in science, demonstrates the potential of engaging scientific diasporas in science education, and enriches connections between the Global South and the Global North.

Evidence supporting a role for astrocytes in the regulation of cognitive flexibility and neuronal oscillations through the Ca2+ binding protein S100ß.

The medial prefrontal cortex (mPFC) is important for cognitive flexibility, the ability to switch between two task-relevant dimensions. Changes in neuronal oscillations and alterations in the coupling across frequency ranges have been correlated with attention and cognitive flexibility. Here we show that astrocytes in the mPFC of adult male Sprague Dawley rats, participate in cognitive flexibility through the astrocyte-specific Ca2+ binding protein S100ß, which improves cognitive flexibility and increases phase amplitude coupling between theta and gamma oscillations. We further show that reduction of astrocyte number in the mPFC impairs cognitive flexibility and diminishes delta, alpha and gamma power. Conversely, chemogenetic activation of astrocytic intracellular Ca2+ signaling in the mPFC enhances cognitive flexibility, while inactivation of endogenous S100ß among chemogenetically activated astrocytes in the mPFC prevents this improvement. Collectively, our work suggests that astrocytes make important contributions to cognitive flexibility and that they do so by releasing a Ca2+ binding protein which in turn enhances coordinated neuronal oscillations.

Bacterial induction of Snail1 contributes to blood-brain barrier disruption.

Bacterial meningitis is a serious infection of the CNS that results when blood-borne bacteria are able to cross the blood-brain barrier (BBB). Group B Streptococcus (GBS) is the leading cause of neonatal meningitis; however, the molecular mechanisms that regulate bacterial BBB disruption and penetration are not well understood. Here, we found that infection of human brain microvascular endothelial cells (hBMECs) with GBS and other meningeal pathogens results in the induction of host transcriptional repressor Snail1, which impedes expression of tight junction genes. Moreover, GBS infection also induced Snail1 expression in murine and zebrafish models. Tight junction components ZO-1, claudin 5, and occludin were decreased at both the transcript and protein levels in hBMECs following GBS infection, and this repression was dependent on Snail1 induction. Bacteria-independent Snail1 expression was sufficient to facilitate tight junction disruption, promoting BBB permeability to allow bacterial passage. GBS induction of Snail1 expression was dependent on the ERK1/2/MAPK signaling cascade and bacterial cell wall components. Finally, overexpression of a dominant-negative Snail1 homolog in zebrafish elevated transcription of tight junction protein-encoding genes and increased zebrafish survival in response to GBS challenge. Taken together, our data support a Snail1-dependent mechanism of BBB disruption and penetration by meningeal pathogens.

Un caso de aneurisma aórtico / A case of aortic aneurysm

Hoy me permito, de manera muy sencilla, relatar un caso de aneurisma con dilatación aórtica que se estudió y trató con el servicio de San Roque en 1928. Se trataba de una enferma de 60 años de edad, natural de Bogotá, hospitalizada el 3 de febrero de 1928 y que quise conservar en el servicio por referirse a una lesión que me llamaba particularmente la atención. Llegó con alguna ligera gripa y no dio antecedentes de mayor importancia. Tuvo fiebre tifoidea en su juventud, no había presentado sino un traumatismo de escasa importancia, y solo había padecido novedades de poca significación. La enferma, en el momento del primer examen, estaba en el lecho en decúbito dorsal, se la notaba algo pálida, pero tenía un aspecto de absoluta tranquilidad, sin fatiga, dolor ni malestar ninguno; contestaba bien a las preguntas y manifestaba haber tenido solamente cefalalgia y dolores óseos nocturnos De la presente observación sacamos las conclusiones siguientes: es mucho lo que sirve para el jefe del servicio y para su ayudante la observación atenta y pormenorizada que se consigna en una observación escrita con relación a cada enfermo; cómo sirve para el hospital este trabajo para facilitar los diagnósticos y hacer más seguro el tratamiento; así como la importancia de la autopsia en muchos casos, tanto para el progreso científico como para aclarar diagnósticos dudosos...(AU)

Manejo de la hiperglucemia en el paciente hospitalizado con diabetes mellitus

La hiperglucemia es un hallazgo frecuente en los pacientes hospitalizados. Está presente en el 40% de los pacientes críticamente enfermos. El paciente con Diabetes Mellitus tipo 2 (DM2) representa el 30% de ellos. En pacientes tratados con insulina se consideran valores seguros de glucemia pre-comidas aquellos alrededor a 140 mg/dL, y casuales menores a 180 mg/dL. Los valores de glucemia entre 110 y 140 mg/dL son recomendados en pacientes con menor riesgo de hipoglucemia. Al hospitalizarse un paciente diabético, se debe calcular de 1,5 a 2 veces la dosis previa de insulina, y en aquellos con hipoglucemiantes orales o debutantes, pueden usarse dosis de insulina a 0,3-0,5 UI/Kg/día. El esquema debe ser individualizado, y se recomienda el que incluye insulina basal (intermedia o lenta), preprandial (rápida) y de corrección (rápida). Se presenta el protocolo que se usa en nuestra Unidad de Endocrinología.

Hyperglycemia is a common finding in hospitalized patients. It is present in 40% of critically ill patients. Patients with type 2 Diabetes Mellitus (T2DM) accounts for 30% of them. The pre-meal glucose levels regarded as safe in patients treated with insulin are those around 140 mg/dL, and casual levels less than 180 mg/dL. Blood glucose levels between 110 and 140 mg/dL are recommended in patients with lower risk of hypoglycemia. When a diabetic patient is hospitalized, calculate 1.5 to 2 times the previous dose of insulin, and in those with oral hypoglycemic agents (OHA) or in debut, the insulin doses may be used at 0.3-0.5 IU/kg/day. The scheme must be individualized, and the use of basal insulin (intermediate or slow), preprandial (fast) and correction (fast) is recommended. The protocol used in our Endocrinology Unit is presented.

The metabolic syndrome during atypical antipsychotic drug treatment: mechanisms and management.

The frequency of obesity, insulin resistance, type 2 diabetes mellitus and other components of metabolic syndrome appear to be significantly elevated in some psychiatric patients. This is a notable example of genetic/environment interaction. Considering the genetic contribution, evidence of insulin resistance in persons with schizophrenia was reported in the pre-pharmacological era. High insulin, glucose, and cortisol levels are observed in first episode psychosis. The frequency of type 2 diabetes mellitus is significantly increased in persons with schizophrenia and bipolar disorder and in their first-degree relatives. Finally, a link exists between schizophrenia and enzymes involved in glycolysis and between antipsychotic drug-induced weight gain and serotonin receptor polymorphism. Important environmental factors are poor dietary habits, smoking, lack of physical exercise, and drug treatment, mostly with antipsychotic drugs (APDs) and perhaps with mood stabilizers. The APDs probably induce metabolic dysfunction by producing sudden appetite increase and weight gain in predisposed subjects. However, direct drug effects on glucose and lipid metabolism independent from body weight change have been proposed. Excessive weight gain is mainly observed with clozapine, olanzapine, chlorpromazine, and thioridazine and is less consistently noted with risperidone or quetiapine. Two recently introduced APDs, ziprasidone and aripiprazole, display a neutral effect on weight and metabolism. Subjects at high risk must be identified early during APD treatment so that provide lifestyle counseling and pharmacological assistance can be provided. The immediate research agenda for the APDs is to improve the animal models of drug-induced metabolic dysfunction; to clarify mechanisms other than weight gain and appetite stimulation; and to test pharmacological agents in randomized, double-blind studies to prevent or reverse metabolic syndrome in selected patients.

Actividad física determinada por podometría en pacientes con síndrome metabólico

Objetivo: El síndrome metabólico (SM) es una entidad clínica caracterizada por un elevado riesgo de complicaciones metabólicas y cardiovasculares. Interesa conocer si existe relación entre la actividad física, medida por podometría, y el diagnóstico de SM y la composición corporal. Métodos: Se incluyeron 39 pacientes adultos de ambos sexos; se diagnosticó SM en 26 de ellos (Grupo de Estudio) y 13 sirvieron de Grupo Control. El contaje de pasos/día se realizó instalando un podómetro digital durante 7 días. Se realizó examen físico y se determinaron la circunferencia abdominal (CA) y el índice de masa corporal (IMC). La composición corporal se determinó por Bioimpedancia Eléctrica obteniéndose: tasa metabólica basal (TMB), porcentaje de grasa corporal (%GC) y masa magra (MM). Resultados: Los individuos con SM presentaron un contaje menor de pasos por día en comparación con aquellos sin SM (2813,9±749,2 frente a 4800,6±1012,5 pasos/día; p<0,0001). El IMC, la CA y el %GC fueron más elevados en pacientes con SM. Se observó una correlación negativa del contaje de pasos por día con la TMB (r= -0,341: p=0,033), el IMC (r= -0,674; p=0,0001), el %GC (r= -0,646; p=0,0001) y la CA (r= -0,638; p=0,0001). Conclusión: El SM se asocia en forma notable con una menor actividad física no estructurada medida por podometría. Se debe considerar la medición por podometría como un método práctico y económico para cuantificar actividad física en individuos y así identificar en forma efectiva personas en condición de riesgo para el desarrollo de complicaciones cardiovasculares y metabólicas.

Objective: The metabolic syndrome (MS) is a clinical entity characterized by a high risk of cardiovascular and metabolic complications. It is interesting to know if there is a relationship between physical activity, measured with a pedometer, with the diagnosis of MS and the body composition. Methods: Thirty-nine adult patients of both sexes were included. MS was diagnosed in 26 of them (Study Group) and the other 13 subjects formed the Control Group. The number of steps per day was obtained by installing a digital pedometer for 7 days. Physical examination was conducted, including abdominal circumference (AC) and body mass index (BMI). The body composition was determined by Electric Bioimpedance, getting basal metabolic rate (BMR), percentage of body fat (% BF) and lean mass (LM). Results: Individuals with MS showed less number of steps per day compared to those without SM (2813.9 ± 749.2 vs 4800.6 ± 1012.5 steps/day, p <0.0001). The BMI, AC and %BF were higher in patients with MS. There was a negative correlation between steps per day and the BMR (r = -0341: p = 0033), BMI (r = -0674, p = 0.0001), %BF (r = -0646, p = 0.0001) and AC (r = -0638, p = 0.0001). Conclusion: The MS is associated with less unstructured physical activity measured with a pedometer. Consideration should be taken to pedometer as a practical and economic method for quantifying physical activity in individuals, and thus, effectively identify people at risk for developing cardiovascular and metabolic complications.