Comparison of the effect of autoclaved and non-autoclaved live soil exposure on the mouse immune system : Effect of soil exposure on immune system.

BACKGROUND: . Lack of exposure to the natural microbial diversity of the environment has been linked to dysregulation of the immune system and numerous noncommunicable diseases, such as allergies and autoimmune disorders. Our previous studies suggest that contact with soil material, rich in naturally occurring microbes, could have a beneficial immunoregulatory impact on the immune system in mice and humans. However, differences in the immunomodulatory properties of autoclaved, sterile soil material and non-autoclaved, live soil material have not been compared earlier. RESULTS: . In this study, we exposed C57BL/6 mice to autoclaved and live soil powders that had the same rich microbiota before autoclaving. We studied the effect of the soil powders on the mouse immune system by analyzing different immune cell populations, gene expression in the gut, mesenteric lymph nodes and lung, and serum cytokines. Both autoclaved and live soil exposure were associated with changes in the immune system. The exposure to autoclaved soil resulted in higher levels of Rorγt, Inos and Foxp3 expression in the colon. The exposure to live soil was associated with elevated IFN-γ concentration in the serum. In the mesenteric lymph node, exposure to live soil reduced Gata3 and Foxp3 expression, increased the percentage of CD8 + T cells and the expression of activation marker CD80 in XCR1+SIRPα- migratory conventional dendritic cell 1 subset. CONCLUSIONS: . Our results indicate that exposure to the live and autoclaved soil powders is not toxic for mice. Exposure to live soil powder slightly skews the immune system towards type 1 direction which might be beneficial for inhibiting type 2-related inflammation. Further studies are warranted to quantify the impact of this exposure in experimental type 2 inflammation.

Null-screen testing of the complementary freeform surfaces of an adjustable focus lens.

A novel null-screen technique to test freeform optical surfaces for ophthalmic use is presented. We present an off-axis experimental setup to evaluate the surface shape of a two-element commercial adaptable focus lens based on the Alvarez principle. The advantages of the method are that it is fast, easy to implement, and reduces costs. This metrology technique is validated by testing both the convex and the concave complementary freeform elements of the spectacle under test. We also apply two methods to recover the surface shape of both elements: numerical integration and a custom probabilistic algorithm. Results are compared with a reference surface finding that for method 1, the RMS value in sagitta differences is 32.6 microns for the convex surface and 26.5 microns for the concave surface. Meanwhile, for method 2, the RMS value in sagitta differences found is 19.8 microns for the convex surface and 16.9 microns for the concave surface. Results show agreement in RMS in sagitta differences for both surfaces in each of the reconstruction methods employed.

Efficacy and safety of FOLFIRI/aflibercept (FA) in an elderly population with metastatic colorectal cancer (mCRC) after failure of an oxaliplatin-based regimen.

BACKGROUND: The VELOUR study showed the benefit of FOLFIRI-Aflibercept (FA) versus FOLFIRI in patients with metastatic colorectal cancer (mCRC) in second-line treatment. However, only 36% of the included patients were ≥65 years. Thus, we seek to evaluate the efficacy and safety of FA in the elderly population in the context of routine practice. MATERIALS AND METHODS: We conducted an observational, retrospective, multicenter, observational study of patients ≥70 years with mCRC treated with FA after progression to oxaliplatin chemotherapy in routine clinical practice in 9 hospitals of the GITuD group. RESULTS: Of 388 patients treated with FA between June 2013 and November 2018, 75 patients ≥70 years were included. The median number of cycles was 10 and the objective response (ORR) and disease control rates (DCR) were 33.8% and 72.0%, respectively. With a median follow-up of 27.1 months, median Progression-free survival (PFS) was 6.6 months and median Overall Survival (OS) was 15.1 months. One third fewer metastasectomies were performed in the ≥75 years' subgroup (24 vs. 52%, p = 0.024) and more initial FOLFIRI dose reductions (68 vs. 36%, p = 0.014). ORR (23.8% vs. 38.3%), DCR (42.8% vs. 85.1%), and PFS (4 vs. 7.8 months; p = 0.017) were significantly less, without difference in OS (9.9 vs. 17.1 months; p = 0.129). The presence of prior hypertension (HT) (PFS 7.9 vs. 5.7 months, p = 0.049) and HT ≥ grade 3 during treatment (PFS 7.6 vs. 6.6 months, p = 0.024) were associated with longer PFS. The most frequent grade 3/4 adverse events were: asthenia (21.3%), neutropenia (14.7%), and diarrhea (14.7%). 57.3% required FOLFIRI dose reduction; 34.7% of aflibercept, including discontinuation (5.3% and 18.7%, respectively). CONCLUSIONS: FA combination is effective in patients ≥70 years. The occurrence of HT is predictive of efficacy. Close monitoring of toxicity and initial dose adjustment is recommended.

The epithelial barrier-protecting properties of a soy hydrolysate.

Enhancing the epithelial barrier function could be a possible strategy to prevent food allergy or reduce its symptoms. Soy hydrolysates containing bioactive peptides could be instrumental in this. In this study, the protective effects of pretreatment with 6 soy hydrolysates on calcium ionophore A23187-induced TEER reduction were studied in T84 cells. The effects of the most potent soy hydrolysate on tight junction gene expression were studied. In order to identify the underlying pathways involved, the barrier disruptor specificity of the effect was studied by comparing the protective effects on TEER and Lucifer Yellow flux after the exposure to barrier disruptors that work via different intracellular pathways, i.e. the disruptors A23187, mellitin, and deoxynivalenol (DON). Preincubation with one of the six hydrolysates protected the epithelial cells from a decrease in TEER induced by A23187 (restored to 105% of the starting point, while A23187 alone decreased to 53% of the starting value) and mellitin (restored to 11% of the starting point, while mellitin alone decreased to 3.8% of the starting value). This soy hydrolysate was found to increase claudin-1 and decrease claudin-2 expression. The protective effect of the hydrolysate on TEER was specific for the barrier disruptors A23187 and mellitin, but was not observed for DON. This observation suggests that the soy hydrolysate may act via PKC isoforms, which are known to lead to changes in the expression of claudin-1 and 2. Our data suggest that specific soy hydrolysates may be designed to strengthen the epithelial barrier which might be instrumental in the management of the barrier function in individuals at risk of developing food allergy.

Characterization of two duplicate zebrafish Cb2-like cannabinoid receptors.

Several cannabinoid receptors have been detected in many organisms. The best known are CB1, mainly expressed in the central nervous system and CB2 which is almost exclusively expressed in the periphery. Here we report the molecular characterization of two duplicate CB2-like cannabinoid receptors from zebrafish (Danio rerio) (zebrafish Cb2a and zebrafish Cb2b). The amino acid sequences of these receptors present 56% identity with Takifugu rubripes CB2 sequence and 39% with human CB2 sequence and conserve some specific key residues for cannabinoid receptor function. Both duplicate receptors are expressed in peripheral tissues (gills, heart, intestine and muscle), immune tissue (spleen) and also in the central nervous system. Using in situ hybridization techniques zebrafish Cb2 mRNA expression was observed for the first time in the adenohypophysial cells of the rostral pars distalis and proximal pars distalis of the pituitary gland. Given the importance of the existence of duplication of genes in teleosts, the combined analysis of these two new cannabinoid receptors opens a new exciting door to investigate and understand cannabinoid function throughout evolution.

Tabaquismo y relación con estilos de vida en una consulta de Atención Primaria / Smoking and relationship with lifestyles in a Primary Care consultation

Objetivo.Estimar la prevalencia de fumadores y relacio-nar tabaquismo con determinados estilos de vida, dietamediterránea, consumo de alcohol y actividad física.Pacientes y métodos.Estudio observacional, descrip-tivo y transversal realizado en pacientes de 18 a 69 años,que acuden a consulta de Atención Primaria durantedos meses y configurada por dos grupos: fumadores yno fumadores. Se realizaron tres cuestionarios estructu-rados y validados: ISCA (Interrogatorio Sistematizadode Consumos Alcohólicos), IPAQ(International PhysicalActivity Questionnaire) y PREDIMED (PREvención conDIeta MEDiterránea). Las encuestas fueron anónimas,supervisadas y asistidas. Los datos se analizaron con elprograma Jamovi, interfaz gráfica (GUI) del lenguajeestadístico R. test Chi-cuadrado para comparar varia-bles categóricas. En todos los contrastes de hipótesisla significación estadística fue p<0,05.Resultados.Muestra de 313 pacientes, 246 no fu-madores y 67 fumadores. Prevalencia de fumadores21,4%. La relación entre dieta y ser fumador y no fu-mador, presenta diferencias no significativas (χ2=10,6;p=0,014) y (OR: 0,615 y IC 95%: 0,352-1,08). Serfumador está relacionado con una menor actividadfísica (χ2=14,5; p=0,002) y (OR: 0,369 y IC 95%:0,197-0,690). Fumar está relacionado con un mayorconsumo de alcohol (χ2=77,6; p<0,001) y (OR: 58,3y IC 95%: 3,56-954).Conclusión.El tabaco es un hábito que condicionaotras conductas poco saludables (más consumo de al-cohol, menor actividad física y menor seguimientode la dieta mediterránea) y, por tanto, es fundamentalque en la deshabituación tabáquica se contemple unabordaje integral del paciente. (AU)

Objective.To estimate the prevalence of smoking andto relate smoking to certain lifestyles, Mediterraneandiet, alcohol consumption and physical activity.Patients and method.Observational, descriptiveand cross-sectional study in patients aged 18 to 69years attending the Primary Care consultation for twomonths and configured by two groups: smokers andnon-smokers. Three structured and validated ques-tionnaires were performed: ISCA (Systematic Alcohol Consumption Questionnaire), IPAQ (InternationalPhysical Activity Questionnaire) and PREDIMED(Mediterranean Diet Prevention). Anonymous, su-pervised and assisted surveys. Data were analizedby Jamovi program, graphic interface (GUI) of thestatistical language R. Test Chi-cuadradoto comparecategorical variables. In all hypothesis contrasts, sta-tistical significance p<0.05.Results.Sample of 313 patients, 246 non-smokersand 67 smokers. Prevalence of smoking 21.4%. Re-lationship between diet and being a smoker and non-smoker presents non-significant differences (χ2=10.6,p=0.014) and (OR: 0.615 and 95% CI: 0.352-1.08).Being a smoker is related to less physical activity(χ2=14.5; p=0.002) and (OR: 0.369 and 95% CI:0.197-0.690). Smoking is related to higher alcoholconsumption (χ2=77.6; p<0.001) and (OR: 58.3 and95% CI: 3.56-954).Conclusion.Tobacco is a habit that conditions otherunhealthy behaviors (more alcohol consumption, lessphysical activity and less adherence to the Medite-rranean diet) and therefore it is fundamental that insmoking cessation a comprehensive approach of thepatient is considered. (AU)

Uso del plasma rico en factores de crecimiento para el tratamiento y prevención de la osteonecrosis mandibular derivada del uso de bifosfonatos / Use of platelet rich in growth factors in the treatment and prevention of osteonecrosis of the jaws in pacients with biphosphonate

Los bifosfonatos (BFs) son fármacos que se utilizan en el tratamiento y prevención de enfermedades relacionadas con el metabolismo óseo. En 2003 se observa, por primera vez, una relación entre la osteonecrosis mandibular (ONJ) y la ingesta de BFs, surgiendo así el concepto BRONJ (biphosphonate-related osteonecrosis of the jaw). Recientemente el uso del plasma rico en factores de crecimiento (PRGF) se ha introducido en el mundo de la odontología por su capacidad regeneradora de tejidos blandos; sin embargo, su papel en el proceso de regeneración de lesiones producidas por cirugías odontológicas está aún por determinar. El objetivo de esta revisión radica en evaluar la eficacia del PRGF en la realización de actos quirúrgicos en pacientes con BRONJ (AU)

Biphosphonates are a commonly used class of drug in the treatment and prevention of diseases-related bone turn over. By the first time, in 2003, the relation between biphosphonates consumption and develop of osteonecrosis of the jaw (ONJ) was established, bring into being the concept of biphosphonate-related osteonecrosis of the jaws (BRONJ). Recently, plasma rich in growth factors (PRGF) has been introduced in dentistry procedures by its regenerative soft tissues capacities; however, its paper in regenerative procedures when surgical lesions appear is still unclear (AU)