B lymphocytes capture antigens from the surface of presenting cells by forming an immune synapse. Local secretion of lysosomes, which are guided to the synaptic membrane by centrosome repositioning, ...can facilitate the extraction of immobilized antigens. However, the molecular basis underlying their delivery to precise domains of the plasma membrane remains elusive. Here we show that microtubule stabilization, triggered by engagement of the B cell receptor, acts as a cue to release centrosome-associated Exo70, which is redistributed to the immune synapse. This process is coupled to the recruitment and activation of GEF-H1, which is required for assembly of the exocyst complex, used to promote tethering and fusion of lysosomes at the immune synapse. B cells silenced for GEF-H1 or Exo70 display defective lysosome secretion, which results in impaired antigen extraction and presentation. Thus, centrosome repositioning coupled to changes in microtubule stability orchestrates the spatial-temporal distribution of the exocyst complex to promote polarized lysosome secretion at the immune synapse.
The engagement of B cells with surface-tethered antigens triggers the formation of an immune synapse (IS), where the local secretion of lysosomes can facilitate antigen uptake. Lysosomes intersect ...with other intracellular processes, such as Toll-like Receptor (TLR) signaling and autophagy coordinating immune responses. However, the crosstalk between these processes and antigen presentation remains unclear. Here, we show that TLR stimulation induces autophagy in B cells and decreases their capacity to extract and present immobilized antigens. We reveal that TLR stimulation restricts lysosome repositioning to the IS by triggering autophagy-dependent degradation of GEF-H1, a Rho GTP exchange factor required for stable lysosome recruitment at the synaptic membrane. GEF-H1 degradation is not observed in B cells that lack αV integrins and are deficient in TLR-induced autophagy. Accordingly, these cells show efficient antigen extraction in the presence of TLR stimulation, confirming the role of TLR-induced autophagy in limiting antigen extraction. Overall, our results suggest that resources associated with autophagy regulate TLR and BCR-dependent functions, which can finetune antigen uptake by B cells. This work helps to understand the mechanisms by which B cells are activated by surface-tethered antigens in contexts of subjacent inflammation before antigen recognition, such as sepsis.
Background. Subjects with type 2 diabetes mellitus (DM2) require an adequate glycemic control to avoid diabetic complications. Currently, saliva biomarkers are used as a diagnostic tool and can be ...indicative of the degree of progression and control of various diseases. Several studies indicate that α-2-macroglobulin levels are elevated in diabetic patients. Methods. 120 subjects with DM2 were enrolled and classified into two groups according to their glycemic control (percentage of glycated hemoglobin-A1c (HbA1c), <7% adequate glycemic control group; >7% inadequate glycemic control group). The relationship between α-2-macroglobulin levels from saliva samples and HbA1c was subsequently evaluated. Results. We found a positive correlation between α-2-macroglobulin and HbA1c (r=0.778 and P<0.0001). Area under the receivers operating characteristic (ROC) curve of α-2-macroglobulin indicated a positive discrimination threshold of α-2-macroglobulin (AUC = 0.903, CI 95%: 0.847–0.959, P<0.0001) to diagnose glycemic control. Conclusions. Our data strongly suggest that the level of saliva α-2-macroglobulin is an indicator for the degree of glycemic control in diabetic patients and represents a promising alternative method to evaluate this parameter.
RESUMEN: Xerostomía o sensación de boca es una afección que afecta severamente la calidad de vida de quienes la padecen. Si bien se relaciona con la reducción del flujo salival (hiposalivación), ...existe evidencia contradictoria y se sugiere evaluar características cualitativas salivales y estado sistémico de los afectados para comprender su etiología y mejorar terapias asociadas. El objetivo de este estudio fue comparar pH y concentración de proteínas en saliva y estado sistémico entre sujetos xerostómicos con y sin hiposialia. Se midió pH, concentración de proteínas salivales y se consignaron antecedentes sistémicos y uso de fármacos en 27 individuos xerostómicos, que fueron divididos en hiposiálicos y no hiposiálicos. Se compararon las variables mencionadas usando test no paramétrico de Mann-Whitney y test Chi-Cuadrado. Se aceptaron diferencias estadísticamente significativas con error alfa igual o menor a 5 %. Sujetos xerostómicos con hiposialia presentaron mayor prevalencia de Artritis Reumatoide y Síndrome de Sjögren en comparación con xerostómicos sin hiposialia. No se encontraron diferencias estadísticamente significativas en relación a pH, concentración de proteínas y uso de medicamentos, variables que no influirían en el padecimiento de xerostomía, independiente de la existencia de hiposialia. Sujetos con xerostomía e hiposialia presentan mayor frecuencia de Artritis Reumatoide y Síndrome de Sjögren.
La xerostomía es una condición crónica que afecta a un alto porcentaje de adultos mayores, que deben ser tratados paliativamente mediante el uso de sustitutos salivales; sin embargo estos productos ...no se encuentran disponibles en el mercado nacional.
Evaluar la eficacia de un nuevo sustituto salival a base de manzanilla y semillas de linaza en la disminución de la sintomatología asociada a xerostomía en individuos adultos mayores.
Se incluyeron 34 voluntarios adultos mayores con xerostomía de diverso origen. Un nuevo sustituto salival a base de manzanilla y semillas de linaza y un sustituto convencional a base de carboximetilcelulosa fueron testados en un ensayo clínico aleatorizado, cruzado, con período de blanqueamiento.
El 100% de los sujetos presentó sensación de boca seca, el 58,8% sensación de saliva espesa, el 52,9% necesitaba beber líquidos para deglutir los alimentos y tenía sensación de dificultad para tragar. La sensación de ardor lingual se registró en el 23,5% de los individuos. Las enfermedades más frecuentes en la muestra analizada fueron la hipertensión arterial y la artritis. Los resultados del ensayo clínico indican que el sustituto salival a base de manzanilla y semillas de linaza disminuye significativamente la sensación de boca seca y la sensación de saliva espesa (test de Wilcoxon p<0,05).
El nuevo sustituto salival a base de manzanilla y semillas de linaza es efectivo en el alivio de la sintomatología asociada a xerostomía en adultos mayores, por lo que puede contribuir a mejorar la calidad de vida de la población afectada por esta condición.
Xerostomia is a common chronic health condition that affects a great number of elderly people. Palliative treatment, such as salivary substitutes should be used, but these products are not accessible in the Chilean market.
To evaluate the efficacy of a new Chamomile and linseed based saliva substitute in the reduction of xerostomía-associated symptomatology in elderly people.
Forty elderly subjects presenting with xerostomia of various origins were selected. Chamomile and linseed based saliva substitute and a carboxymethylcellulose based conventional artificial saliva were tested using a double-blind, randomized, cross-over clinical trial with an intervining wash out period.
All (100%) of subjects had a sensation of dry mouth, and 58.8% mentioned a sensation of thick saliva, 52.9% needed to drink liquids to swallow, and with a sensation of swallowing difficulty. Burning tongue sensation was recorded in 23.5% of the patients. The most frequent pathologies in the sample were arterial hypertension and arthritis. Results of the clinical tests showed that Chamomile and linseed based saliva substitute significantly relieves the sensation of dry mouth and the sensation of thick saliva (Wilcoxon test P<.05).
New chamomile and linseed based saliva substitute was effective in relieving xerostomia symptoms in elderly people, and could improve the quality of life of population affected by this condition.
Background Intensive training programs arose from limitations in access to simulation centers. The aim of this study is to evaluate the effect and associated factors involved in an intensive course ...for learning advanced laparoscopic skills, which include validated teaching techniques. Methods General surgeons and final-year residents were analyzed after completing an intensive 5-session advanced laparoscopy course. Initial (IA) and final assessment (FA) consisted in performing a jejunojejunal anastomosis in a live porcine model, measured using objective structured assessment of technical skill (OSATS) (GRS and SRS, that is, global rating scale and specific rating scale, respectively) and operative time (OT). The 3-session training was structured in a bench model with an ex vivo bowel. For the demographic analysis, 3 groups were defined according to the presentation of relevant changes in OSATS and in OT between IA and FA: group A, no changes; group B, change in 1 variable; and group C, change in both variables. Results After the course, all 114 participants presented a significant improvement in OT (37 vs 24.6 min, p < 0.001) and in OSATS; global rating scale (10.5 vs 16 points; p < 0.001) and Specific Rating Scale (8.5 vs 12.7 points; p < 0.001). In the IA, 70 (61%) participants completed the jejunojejunal anastomosis and 105(92%) in the FA (p < 0.01). In the FA, 56% of participants presented relevant changes in both variables (group C). This group was significantly younger (34 vs 45 vs 40 y old; p < 0.001), had fewer years of surgical experience (2 vs 9 vs 5 y; p < 0.001), and had a proportionally higher concentration of residents (p = 0.01). Conclusions This intensive course is set out as a viable alternative to teach basic skills in advanced laparoscopy in a short period of time, which is ideal for surgeons with difficult access to training centers. It remains necessary to establish the participant profile for which this type of course is most beneficial.
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