TLR4 polymorphism and haplotype are associated with obesity and lipid profile in young population: a pilot study.

BACKGROUND: The single nucleotide polymorphisms in the TLR4 gene can decrease or increase the response to lipopolysaccharide, increasing the susceptibility to inflammatory diseases, affecting the expression or receptor function by inducing a low-grade chronic inflammatory response. PURPOSE: The objective of this study was to evaluate the association of SNPs - 2570 A > G (rs2737190), - 2081 G > A (rs10983755), 896 A > G (rs 4986790), and 1196 C > T (rs4986791) of the TLR4 gene with obesity and metabolic alterations in the young population. RESULTS: In this study, it was found that the carriers of the heterozygous genotype of the SNPs - 2081 G > A, 896 A > G, and 1196 C > T confer a higher risk of developing obesity (OR = 3.73, p = 0.018; OR = 5.66, p = 0.014, and OR = 8.95, p = 0.014, respectively). Also, with the lipid profile, the SNP - 2081 G > A was associated with total cholesterol (TC) ≥ 200 mg/dL (OR = 3.91, p = 0.020) and Kannel index > 3% (OR = 4.00, p = 0.008). The SNP 896 A > G was associated with LDL-c ≥ 100 mg/dL (OR = 3.64, p = 0.040) and Kannel index > 3% (OR = 4.33, p = 0.016), and the SNP 1196 C > T was associated with TC ≥ 200 mg/dL (OR = 4.37, p = 0.048), Castelli index > 4.5/> 5% (OR = 5.33, p = 0.016), and Kannel index > 3% (OR = 16.00, p = 0.001). Finally, the AGGT haplotype was associated with Castelli index > 4.5/> 5% (OR = 5.40, p = 0.015) and Kannel index > 3% (OR = 10.46, p < 0.001), and the AAAC haplotype was associated with obesity (OR = 3.56, p = 0.020), TC ≥ 200 mg/dL (OR = 4.04, p = 0.007), LDL-c ≥ 100 mg/dL (OR = 2.98, p = 0.030) and Kannel index > 3% (OR = 4.20, p = 0.002). CONCLUSION: The heterozygous genotype of the SNPs - 2081 G > A, 896 A > G and 1196 C > T of the TLR4 gene was associated with altered lipid profile and development of obesity in young university students of Guerrero State, Mexico.

Combination of white matter hyperintensities and Aß burden is related to cognitive composites domain scores in subjective cognitive decline: the FACEHBI cohort.

BACKGROUND: To explore whether the combination of white matter hyperintensities (WMHs) and amyloid-beta (Aß) deposition is associated with worse cognitive performance on cognitive composites (CCs) domain scores in individuals with subjective cognitive decline (SCD). METHODS: Two hundred participants from the FACEHBI cohort underwent structural magnetic resonance imaging (MRI), 18F-florbetaben positron emission tomography (FBB-PET), and neuropsychological assessment. WMHs were addressed through the Fazekas scale, the Age-Related White Matter Changes (ARWMC) scale, and the FreeSurfer pipeline. Eight CCs domain scores were created using the principal component analysis (PCA). Age, sex, education, and apolipoprotein E (APOE) were used as adjusting variables. RESULTS: Adjusted multiple linear regression models showed that FreeSurfer (B - .245; 95% CI - .1.676, - .393, p = .016) and ß burden (SUVR) (B - .180; 95% CI - 2.140, - .292; p = .070) were associated with face-name associative memory CCs domain score, although the latest one was not statistically significant after correction for multiple testing (p = .070). There was non-significant interaction of these two factors on this same CCs domain score (p = .54). However, its cumulative effects on face-name associative performance indicated that those individuals with either higher WMH load or higher Aß burden showed the worst performance on the face-name associative memory CCs domain score. CONCLUSIONS: Our results suggest that increased WMH load and increased Aß are independently associated with poorer episodic memory performance in SCD individuals, indicating a cumulative effect of the combination of these two pathological conditions in promoting lower cognitive performance, an aspect that could help in terms of treatment and prevention.

High leucine levels affecting valine and isoleucine recommendations in low-protein diets for broiler chickens.

Four experiments were conducted to estimate the optimal standardized ileal digestible (SID) level of branched-chain amino acids in low-protein diets during the starter, grower, and finisher periods, using the response surface methodology, and to study their effects on performance and mRNA expression of genes involved in the mechanistic target of rapamycin (mTOR) pathway of broiler chickens from 8 to 21 D of age. In experiments 1, 2, and 3, a total of 1,500 Cobb male broiler chickens were assigned to 15 diets of a central composite rotatable design (CCD) of response surface methodology containing 5 levels of SID Leu, Val, and Ile with 5 replicate pens of 20 birds each. A 3-factor, 5-level CCD platform was used to fit the second-order polynomial equation of broiler performance. In experiment 4, a total of 540 8-day-old Cobb male broiler chickens were distributed in a completely randomized 2 x 3 x 3 factorial arrangement with 2 SID Leu levels (1.28 or 1.83%), 3 SID Val levels (0.65, 0.90, or 1.20%), and 3 SID Ile levels (0.54, 0.79, or 1.09%) for a total of 18 treatments with 5 replicate cages of 6 birds each. High Leu levels impaired (P < 0.05) gain:feed when birds were fed marginal Val or Ile diets. However, gain:feed was restored when both Val and Ile were supplemented to reach adequate or high levels. High Leu levels increased (P < 0.05) mRNA expression of S6K1 and eEF2 genes only in birds fed high Ile levels. Dietary SID Leu, Val, and Ile levels required for gain:feed optimization in low-protein diets were estimated at 1.37, 0.94, and 0.87% during the starter period; 1.23, 0.82, and 0.75% during the grower period; and 1.15, 0.77, and 0.70% during the finisher phase, respectively. Higher Val and Ile levels are required to optimize the effect of Leu supplementation on mRNA expression of mTOR pathway genes in the pectoralis major muscle of broilers from day 1 to 21 after hatch.

A framework to bridge scales in distribution modeling of soil microbiota.

Creating accurate habitat suitability and distribution models (HSDMs) for soil microbiota is far more challenging than for aboveground organism groups. In this perspective paper, we propose a conceptual framework that addresses several of the critical issues holding back further applications. Most importantly, we tackle the mismatch between the broadscale, long-term averages of environmental variables traditionally used, and the environment as experienced by soil microbiota themselves. We suggest using nested sampling designs across environmental gradients and objectively integrating spatially hierarchic heterogeneity as covariates in HSDMs. Second, to incorporate the crucial role of taxa co-occurrence as driver of soil microbial distributions, we promote the use of joint species distribution models, a class of models that jointly analyze multiple species' distributions, quantifying both species-specific environmental responses (i.e. the environmental niche) and covariance among species (i.e. biotic interactions). Our approach allows incorporating the environmental niche and its associated distribution across multiple spatial scales. The proposed framework facilitates the inclusion of the true relationships between soil organisms and their abiotic and biotic environments in distribution models, which is crucial to improve predictions of soil microbial redistributions as a result of global change.

A potential inflammatory role of IL-31 in psoriatic arthritis: A correlation with Th17 cytokine profile.

The goals of our study were to determine the possible association of interleukin (IL)-31 with Th17 cytokine profile in serum and to quantify retinoic acid-related orphan receptor C (RORC) mRNA expression in psoriatic arthritis (PsA) patients. This cross-sectional study was conducted in 50 patients with PsA and 30 control subjects (CS) matched by age and gender. The cytokine serum levels were quantified by magnetic bead-based assay using the Bio-Plex MAGPIX system, and RORC mRNA expression was determined by quantitative polymerase chain reaction (qPCR). As a result, significant differences in IL-31 were observed between study groups (77.23 pg/mL in PsA vs 64.4 pg/mL in CS, P < 0.001) and Th17 cytokine profile serum levels (IL-17A: 6.36 pg/mL in PsA vs 2.97 pg/mL in CS, P = 0.02; IL-17F: 44.15 pg/mL in PsA vs 23.36 pg/mL in PsA, P = 0.01; IL-17E: 3.03 pg/mL in PsA vs 0.82 pg/mL in CS, P < 0.001; IL-21: 36.45 pg/mL in PsA vs 12.44 pg/mL in CS, P = 0.02); however, significant differences were not observed for IL-23 (31.2 pg/mL in PsA vs 53.26 pg/mL in CS, P = 0.58). Furthermore, positive correlations between IL-31 and Th17 cytokine profile serum levels were found (IL-17A: rs = 0.64, P < 0.001; IL-17F: rs = 0.73, P < 0.001; IL-17E: rs = 0.70, P < 0.001; IL-21: rs = 0.54, P = 0.002; IL-23: rs = 0.5, P < 0.01). Regarding RORC gene expression, the PsA group showed an increase of 6.85-fold compared to the CS group. We did not find any association between the serum levels of cytokines and RORC gene expression. In conclusion, in PsA, there are increased serum levels of IL-31, IL-17A, IL-17F, IL-17E, and IL-21, but not IL-23. Moreover, there was a positive correlation of IL-31 with the Th17 cytokine profile and a high RORC gene expression. Altogether, these findings suggest a proinflammatory contribution of IL-31 in close association with the Th17 cytokine profile in PsA.

The -675 4G/5G PAI-1 polymorphism confers genetic susceptibility to systemic lupus erythematosus, its clinical manifestations, and comorbidities in Mexican-Mestizo population.

Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the development of SLE, and the -675 4G/5G PAI-1 polymorphism has been associated with several pathologies with a chronic inflammatory component. Our objective was to investigate the genetic association between the -675 4G/5G PAI-1 polymorphism with SLE, its clinical manifestations, and comorbidities in a Mexican-Mestizo population. The -675 PAI-1 polymorphism was determined by PCR-RFLP in 716 subjects: 293 SLE patients and 423 control subjects. Significant associations for SLE genetic susceptibility were found in carriers of 4G/5G (OR = 2.63; CI 1.81-3.87; p < .001) and 4G/4G (OR = 2.70; CI 1.62-4.51; p < .001) genotype in comparison with the 5G/5G genotype; 4G allele carriers also presented genetic risk for SLE (OR = 1.63; CI 1.31-2.03; p < .001) compared to the 5G allele. Following a dominant genetic model, a similar association was found with the 4G allele to SLE (OR = 2.66; CI1.84-3.84; p < .001). The 4G/5G genotype was associated with shorter disease duration (p = .039), as well as lower levels of haemoglobin (p = .001) and haematocrit (p = .009); the need for prednisone treatment (p = .001), higher BMI (p = .03), presence of type 2 DM (p = .015), clinical activity (Mex-SLEDAI = 57%; p = .047), Chronicity (SLICC-ACR = 0; p = .015) and CRP levels (p = .015) were associated with 5G/5G genotypes. In conclusion, the -675 4G/5G and 4G/4G PAI-1genotypes were found as genetic risk markers of susceptibility for SLE in the Mexican-Mestizo population, and each genotype could influence the clinical manifestations and comorbidities differently in SLE.

Genome Wide Meta-Analysis identifies common genetic signatures shared by heart function and Alzheimer's disease.

Echocardiography has become an indispensable tool for the study of heart performance, improving the monitoring of individuals with cardiac diseases. Diverse genetic factors associated with echocardiographic measures have been previously reported. The impact of several apoptotic genes in heart development identified in experimental models prompted us to assess their potential association with human cardiac function. This study aimed at investigating the possible association of variants of apoptotic genes with echocardiographic traits and to identify new genetic markers associated with cardiac function. Genome wide data from different studies were obtained from public repositories. After quality control and imputation, a meta-analysis of individual association study results was performed. Our results confirmed the role of caspases and other apoptosis related genes with cardiac phenotypes. Moreover, enrichment analysis showed an over-representation of genes, including some apoptotic regulators, associated with Alzheimer's disease. We further explored this unexpected observation which was confirmed by genetic correlation analyses. Our findings show the association of apoptotic gene variants with echocardiographic indicators of heart function and reveal a novel potential genetic link between echocardiographic measures in healthy populations and cognitive decline later on in life. These findings may have important implications for preventative strategies combating Alzheimer's disease.

Parámetros basales de la espirometría que pueden influir en la prueba de broncodilatación / Baseline spirometry parameters that can influence the bronchodilation test

OBJETIVO: Estudiar si los parámetros basales de la espirometría forzada pueden influir en la positividad de la prueba de broncodilatación (PBD) y si esto pudiera influir en futuros criterios de positividad. MATERIAL Y MÉTODOS: Estudio descriptivo transversal multicéntrico con emplazamiento en Atención Primaria. Fueron incluidos todos los pacientes derivados por su médico de familia, para la realización de espirometría forzada por tabaquismo, síntomas respiratorios o seguimiento de enfermedades respiratorias, entre los meses de junio de 2015 y febrero de 2017. A todos ellos se les realizó una espirometría forzada con PBD. RESULTADOS: Se incluyeron 295 pacientes, con una edad media de 53,4+/-15,5 años, el 62% fueron hombres. En el 20% de las espirometrías se obtuvo un patrón obstructivo; presentando el 67,5% una obstrucción leve, 18% moderada, 9,6% moderada-grave y un 4,8% muy grave. El 8,8% de las espirometrías obtuvieron PBD positiva; 11,2% fueron positivas únicamente en volumen y el 17,6% fueron positivas únicamente en porcentaje. Se observó que los pacientes con una PBD positiva en porcentaje presentaban de forma basal menor volumen espiratorio forzado en el primer segundo (1,66 l/sg vs.2,74 l/sg; p <0,001), y menor capacidad vital forzada (2,85 l vs.3,73 l; p < 0,001). Los pacientes con PBD positiva en volumen presentaban menor volumen espiratorio forzado en el primer segundo (2,59 l/sg vs.2,62 l/sg; p <0,001), y mayor capacidad vital forzada (3,89 l vs.3,58 l; p < 0,001). CONCLUSIONES: El volumen espiratorio forzado en el primer segundo y la capacidad vital forzada basales influyen en la positividad de la PBD. Debería valorarse esta circunstancia a la hora de establecer los criterios de positividad de la PBD

OBJECTIVE: To determine whether the baseline parameters of forced spirometry can influence the positivity of the bronchodilation test (BDT), and whether this could have an influence in future positivity criteria. MATERIAL AND METHODS: A descriptive, cross-sectional study was conducted in a Primary Care setting. It included all patients referred by their family doctor to perform a forced spirometry test due to smoking, respiratory symptoms, or follow-up of respiratory diseases, between the months of June 2015 and February 2017. All of them were subjected to a forced spirometry with a BDT. RESULTS: A total of 295 patients were included, with a mean age 53.4+/-15.5 years, and 62% were male. An obstructive pattern was obtained in 20% of the spirometries, with 67.5% presenting with a mild obstruction, 18% a moderate, 9.6% moderate to severe, and 4.8% very severe. The BDT was positive in 8.8% of the spirometries, with 11.2% only positive in volume, and 17.6% were only positive in percentage. It was observed that the patients with a BDT positive in percentage had a lower base forced expiry volume in the first second (1.66 L/sec vs.2.74 L/sec; P<.001), and a lower forced vital capacity (2.85 l vs.3.73 l; P<.001). The patients with a positive BDT in volume had a lower forced expiry volume in the first second (2.59 l/sec vs.2.62 l/sec; P<.001), and a higher forced vital capacity (3.89 l vs.3.58 l; P<.001). CONCLUSIONS: The baseline forced expiry volume in the first second and forced vital capacity have an influence in the positivity of the BDT. This circumstance should be assessed when establishing the positivity of the BDT

Riesgo de declive funcional en pacientes ancianos no institucionalizados / Functional decline risk in elderly patients not institutionalized

OBJETIVO: Valorar el riesgo de declive funcional (DF) mediante varias escalas de predicción. MATERIAL Y MÉTODOS: Estudio multicéntrico, observacional y corte transversal, dirigido a una población de 70 años o más del área de salud de Toledo. Se excluyeron los pacientes institucionalizados, terminales y dependientes para 3 o más actividades básicas de la vida diaria. La muestra (480 pacientes), fue calculada para: prevalencia DF estimada del 15%, precisión 2%, nivel de confianza 95 y 10% de pérdidas estimadas. Muestreo estratificado, primero por conglomerados (centros de salud) y posteriormente muestreo sistemático (1/15) por listado de pacientes ordenados por edad. Tasa de respuesta: 98%. VARIABLES: Sociodemográficas, de morbilidad, cuestionarios para evaluar la capacidad funcional para las actividades básicas (índice de Katz) e instrumentales (índice de Lawton-Brody) de la vida diaria y reglas de predicción de riesgo de DF (SHERPA, TRST, ISAR-PC e Inouye). Aprobado por el Comité Ético de Investigación Clínica de Toledo. RESULTADOS: Media de edad: 77,94 (DS: 6,27) años, el 54,4% mujeres. Media de enfermedades: 4,38 (DS: 2,17) y de fármacos: 5,57 (DS: 3,35). Riesgo de DF según las reglas de predicción: SHERPA: 32,7% (IC95%: 28,52-36,88) (riesgo leve: 17,2% [IC95%: 13,83-20,57]; moderado: 9,7% [IC95%: 7,06-12,34] y alto: 5,8% [IC95%: 3,72-7,88]); TRST: 42% (IC95%: 37,6-46,4); ISAR-PC: 75,4% (IC95%: 71,14-78,86); Inouye: 49,3% (IC95% 44,84-53,76) (riesgo medio: 44,5% [IC95%: 40,07-48,93] y riesgo alto: 4,8% [IC95%: 2,89-6,71]). CONCLUSIONES: Porcentaje importante de pacientes en riesgo de DF, pero gran variabilidad entre las distintas reglas. En general, el riesgo es inferior al encontrado en otros estudios, siendo necesario validar nuevas reglas adaptadas a nuestro medio

OBJECTIVE: To assess the risk of functional decline (DF) by using several prediction scales. MATERIAL AND METHODS: A multicentre, observational, cross-sectional study was conducted on a population of 70 years or more in the health area of ??Toledo. Institutionalised, terminal ill, and patients dependent for three or more basic activities of daily life, were excluded. The sample (480 patients) was calculated for an estimated DF prevalence of 15%, accuracy 2%, confidence level 95%, and 10% of estimated losses. Stratified sampling; first by conglomerates (Health Centres) and then systematic sampling (1/15) by list of patients ordered by age. Response rate: 98%. VARIABLES: Sociodemographic, morbidity, questionnaires to assess the functional capacity for basic activities (Katz index), and tools (Lawton-Brody index) of daily life and risk prediction rules of DF (SHERPA, TRST, ISAR-PC and Inouye). Approved by the Clinical Research Ethics Committee of Toledo. RESULTS: The mean age was 77.94 (SD: 6.27), with 54.4% women. Mean number of illnesses: 4.38 (SD: 2.17) and drugs: 5.57 (SD: 3.35). Risk of DF according to the prediction rules: SHERPA: 32.7% (95% CI: 28.52-36.88) (slight risk: 17.2% [95% CI: 13.83-20.57]; moderate: 9.7% [95% CI: 7.06-12.34] and high: 5.8% [95% CI: 3.72-7.88]); TRST: 42% (95% CI: 37.6-46.4); ISAR-PC: 75.4% (95% CI: 71.14-78.86); Inouye: 49.3% (95% CI: 44.84-53.76) (mean risk: 44.5% [95% CI: 40.07-48.93], and high: risk 4.8% [95% CI: 2.89-6.71]). CONCLUSIONS: A significant percentage of patients are at risk of DF, but there is a wide variation between the different rules. In general, the risk is lower than that found in other studies, and it is necessary to validate new rules adapted to our environment

Células osteogénicas afectadas por los factores solublestumorales contribuyen a la formación del nichopre-metastásico óseo / Osteogenic cells affected by soluble tumor factorscontribute to bone pre-metastatic niche formation

Objetivo: Analizar el efecto de los secretomas de tumores sólidos organotrópicos hacia el hueso en células de linaje osteogénico, de tipo osteoblástico y osteocítico, en la expresión de genes relacionados con el metabolismo óseo. Material y método: Caracterizamos los cambios en expresión génica por PCR cuantitativa a tiempo real del eje OPG/RANKL, así como de otros genes relacionados con la diferenciación osteoblástica como son Runx2 y osteocalcina, inducidos por los medios condicionados de células tumorales prostáticas, mama y melanoma en pre‐osteoblastosMC3T3‐E1 y osteocitos MLO‐Y4 murinos o en osteoblastos humanos, según correspondiese por especie. Resultados: La estimulación de las células osteocíticas con medios condicionados de células de melanoma o adenocarcinoma prostático indujo un incremento en la expresión génica de OPG y también de RANKL, viéndose incrementado la ratio OPG/RANKL. Únicamente el secretoma de las células de adenocarcinoma prostático alteró la expresión de Runx2en osteocitos. Los medios condicionados de células de cáncer de mama modificaron únicamente la expresión de RANKLen células osteoblásticas, viéndose disminuido la ratioOPG/RANKL. Conclusión: Los factores solubles tumorales tienen como diana celular a las células osteocíticas, favoreciendo la inducción de un nicho pre‐metastásico óseo por modificación de la ratio OPG/RANKL en el entorno óseo, y, con ello, la progresión de tumores organotrópicos óseos como son el melanoma y adenocarcinomas prostático

Objective: To analyze the effect of the secrets of solid organotropic tumors towards bone in osteogenic, osteoblastic and osteocytic lineage cells, in the expression of genes related to bone metabolism. Material and method: We characterize the changes in gene expression by quantitative real‐time PCR of the OPG/RANKL axis, as well as other genes related to osteoblastic differentiation such as Runx2 and osteocalcin, induced by the conditioned means of prostate tumor cells, breast and melanoma in pre MC3T3‐E1 osteoblasts and murine MLO‐Y4 osteocytes or in human osteoblasts, as appropriate by species. Results: Stimulation of osteocitic cells with conditioned means of melanoma or prostate adenocarcinoma cells inducedan increase in OPG and RANKL gene expression, with the OPG/RANKL ratio being increased. Only the secretome of prostate adenocarcinoma cells altered the expression of Runx2 in osteocytes. Conditioned media of breast cancer cellsonly modified the expression of RANKL in osteoblast cells, with a decrease in OPG/RANKL ratio. Conclusion: Soluble tumor factors have osteocitic cells as their cellular target, favoring the induction of a pre‐metastatic bone niche by modifying the OPG/RANKL ratio in the bone environment, and, thus, the progression of bone organo‐tropic tumors such as melanoma and prostatic adenocarcinomas

[Functional decline risk in elderly patients not institutionalized]. / Riesgo de declive funcional en pacientes ancianos no institucionalizados.

OBJECTIVE: To assess the risk of functional decline (DF) by using several prediction scales. MATERIAL AND METHODS: A multicentre, observational, cross-sectional study was conducted on a population of 70 years or more in the health area of ??Toledo. Institutionalised, terminal ill, and patients dependent for three or more basic activities of daily life, were excluded. The sample (480 patients) was calculated for an estimated DF prevalence of 15%, accuracy 2%, confidence level 95%, and 10% of estimated losses. Stratified sampling; first by conglomerates (Health Centres) and then systematic sampling (1/15) by list of patients ordered by age. Response rate: 98%. VARIABLES: Sociodemographic, morbidity, questionnaires to assess the functional capacity for basic activities (Katz index), and tools (Lawton-Brody index) of daily life and risk prediction rules of DF (SHERPA, TRST, ISAR-PC and Inouye). Approved by the Clinical Research Ethics Committee of Toledo. RESULTS: The mean age was 77.94 (SD: 6.27), with 54.4% women. Mean number of illnesses: 4.38 (SD: 2.17) and drugs: 5.57 (SD: 3.35). Risk of DF according to the prediction rules: SHERPA: 32.7% (95% CI: 28.52-36.88) (slight risk: 17.2% [95% CI: 13.83-20.57]; moderate: 9.7% [95% CI: 7.06-12.34] and high: 5.8% [95% CI: 3.72-7.88]); TRST: 42% (95% CI: 37.6-46.4); ISAR-PC: 75.4% (95% CI: 71.14-78.86); Inouye: 49.3% (95% CI: 44.84-53.76) (mean risk: 44.5% [95% CI: 40.07-48.93], and high: risk 4.8% [95% CI: 2.89-6.71]). CONCLUSIONS: A significant percentage of patients are at risk of DF, but there is a wide variation between the different rules. In general, the risk is lower than that found in other studies, and it is necessary to validate new rules adapted to our environment.

PRL -1149T allele (rs1341239) is associated with decreased risk of rheumatoid arthritis in population from southern Mexico: analysis of mRNA expression and PRL serum levels.

INTRODUCTION: Prolactin (PRL) is a sex hormone with immunomodulatory properties, and it is associated with the clinical activity of rheumatoid arthritis (RA). The -1149G>T polymorphism at the prolactin (PRL) gene has been associated with autoimmune diseases, but its functional effect is unclear. OBJECTIVE: To analyze the association of the PRL -1149G>T polymorphism with disease susceptibility, mRNA, and protein expression of PRL in RA patients from Southern Mexico. METHODS: We included 300 RA patients and 300 control subjects (CS). Genotypes were identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, the PRL mRNA expression was determined by real-time PCR, and PRL serum levels were measured by enzyme-linked immunosorbent assay. RESULTS: Applying genetic models of inheritance (dominant, recessive, and additive), we found an association between the T allele and decreased RA susceptibility (OR = 0.55, 95% CI 0.35-0.87, p = 0.009; OR = 0.09, 95% CI 0.012-0.76, p = 0.011; OR = 0.49, 95% CI 0.32-0.76, p = 0.001, respectively). RA patients had higher mRNA expression and soluble levels of PRL than CS (p < 0.05). The PRL serum levels were similar in RA and CS according to genotypes. However, in CS, carriers of GT and TT genotypes showed lower PRL mRNA expression than GG genotype carriers (7.1-fold and 20-fold respectively, p = 0.006). CONCLUSIONS: This study demonstrated that the PRL -1149T allele is a genetic marker of decrease risk to RA in population from Southern Mexico, and it is associated with low PRL mRNA. KEY POINTS: • PRL -1149T allele is a marker of decreased RA susceptibility in population from southern Mexico. • PRL -1149TT genotype is associated with low PRL mRNA expression. • RA patients have higher mRNA expression and soluble levels of PRL than healthy subjects. • PRL serum levels are higher in those RA patients with < 2 years of disease evolution.

[Baseline spirometry parameters that can influence the bronchodilation test]. / Parámetros basales de la espirometría que pueden influir en la prueba de broncodilatación.

OBJECTIVE: To determine whether the baseline parameters of forced spirometry can influence the positivity of the bronchodilation test (BDT), and whether this could have an influence in future positivity criteria. MATERIAL AND METHODS: A descriptive, cross-sectional study was conducted in a Primary Care setting. It included all patients referred by their family doctor to perform a forced spirometry test due to smoking, respiratory symptoms, or follow-up of respiratory diseases, between the months of June 2015 and February 2017. All of them were subjected to a forced spirometry with a BDT. RESULTS: A total of 295 patients were included, with a mean age 53.4±15.5 years, and 62% were male.An obstructive pattern was obtained in 20% of the spirometries, with 67.5% presenting with a mild obstruction, 18% a moderate, 9.6% moderate to severe, and 4.8% very severe. The BDT was positive in 8.8% of the spirometries, with 11.2% only positive in volume, and 17.6% were only positive in percentage. It was observed that the patients with a BDT positive in percentage had a lower base forced expiry volume in the first second (1.66 L/sec vs. 2.74 L/sec; P<.001), and a lower forced vital capacity (2.85 l vs.3.73 l; P<.001). The patients with a positive BDT in volume had a lower forced expiry volume in the first second (2.59 l/sec vs. 2. 62 l/sec; P<.001), and a higher forced vital capacity (3.89 l vs. 3.58 l; P<.001). CONCLUSIONS: The baseline forced expiry volume in the first second and forced vital capacity have an influence in the positivity of the BDT. This circumstance should be assessed when establishing the positivity of the BDT.

Manejo laparoscópico multidisciplinario de la endometriosis profunda del 2010 al 2017: estudio de cohorte retrospectivo / Multidisciplinary laparoscopic management of deep infiltrating endometriosis from 2010 to 2017: A retrospective cohort study

INTRODUCCIÓN La laparoscopía es actualmente el estándar en el manejo de la endometriosis profunda. Sin embargo, requiere de un entrenamiento específico e involucra la realización de procedimientos complejos y asociados a una alta tasa de complicaciones. Por lo anterior en Chile y Latinoamérica, la endometriosis profunda es frecuentemente manejada de manera inadecuada. OBJETIVO Describir nuestra experiencia en el enfrentamiento clínico y manejo quirúrgico laparoscópico de la endometriosis profunda, durante los últimos siete años. MÉTODOS Estudio de cohorte retrospectivo de 137 pacientes consecutivas operadas y con confirmación histológica de endometriosis profunda. Se recolectaron los datos demográficos, datos quirúrgicos, complicaciones, resultados reproductivos y seguimiento. RESULTADOS Todas las cirugías fueron completadas por laparoscopía, sin conversión. La dismenorrea y la dispareunia fueron los síntomas más frecuentes en 85,4 y 56,9%, respectivamente. La localización más frecuente de endometriosis profunda fueron los ligamentos úterosacros, coexistiendo un endometrioma en 48,9% de los casos. La mediana de tiempo operatorio fue de 140 minutos, siendo significativamente más prolongado en casos con compromiso intestinal (p < 0,0001). Quince pacientes (10,9%) presentaron complicaciones. El seguimiento medio fue de 24,5 meses. La tasa de embarazo fue de 58,1% y 90% de las pacientes reportó una mejoría significativa de su sintomatología. CONCLUSIONES El manejo laparoscópico de la endometriosis profunda es efectivo y seguro, pero debe reservarse a centros especializados y con disponibilidad de equipo multidisciplinario.

BACKGROUND Laparoscopy has become the standard of care in the surgical management of deep infiltrating endometriosis (DIE). However, it is a challenging procedure with a high complication rate. Despite the benefits of the minimally invasive approach, DIE resection is often performed by surgeons without adequate training, especially in developing countries like Chile. OBJECTIVE To asses our experience in the diagnosis and laparoscopic management of DIE during seven years. METHODS A retrospective cohort study of data including 137 patients with pathology-proven DIE. Surgical and fertility outcomes were evaluated. RESULTS All procedures were performed laparoscopically without conversion. Dysmenorrhea and dyspareunia were the most common symptoms in 85.4% and 56.9%, respectively. Uterosacral ligaments were the most common DIE location. Endometrioma was present in 48.9% of cases. Median operative time was 140 minutes; however, it was longer in cases requiring bowel surgery (p < 0.0001). The complication rate was 10.9%. Median follow-up was 24.5 months. The pregnancy rate was 58.1% and 90% of patients reported significant symptom relief after surgery. CONCLUSION Laparoscopic surgical management of DIE is effective and safe but it must be performed in tertiary centers with the availability of multidisciplinary teams.

Factores secretados por células óseas inducen acumulación de calcio intracelular y AMP cíclico y activación de ERK 1/2 en células de cáncer de próstata; evaluación por técnicas de fluorescencia en células vivas / Factors secreted by bone cells induce intracellular calcium accumulation and cyclic AMP and activation of ERK 1/2 in prostate cancer cells; evaluation by fluorescence techniques in living cells

Objetivos: Analizar en células tumorales de próstata los efectos causados por el secretoma de células óseas sobre la proliferación y sobre vías de señalización intracelular relacionadas con la progresión del cáncer de próstata. Materiales y métodos: Se caracterizaron los efectos de factores secretados presentes en medios condicionados de pre-osteoblastos MC3T3-E1 y osteocitos MLO-Y4 sobre la proliferación de células de adenocarcinoma de próstata metastásicas PC-3 mediante tinción por azul de tripano. Se observó por técnicas de fluorescencia en células vivas los efectos de los medios condicionados por células MC3T3-E1 y MLO-Y4 en moléculas de señalización intracelular implicadas en la progresión tumoral de células de adenocarcinoma de próstata PC-3. Se estudió la acumulación de calcio intracelular utilizando el indicador de calcio fluorescente Fluo-4AM y la generación de AMP cíclico, y la activación de la quinasa ERK 1/2 por Transferencia de Energía de Resonancia Fluorescente (FRET) usando los biosensores EPAC y ERK-NES, respectivamente. Resultados: La estimulación de células PC-3 con medios condicionados de pre-osteoblastos MC3T3-E1 y osteocitos MLO-Y4 indujo aumento en la proliferación de las células de adenocarcinoma PC-3. Los medios condicionados por células óseas causaron también aumento transitorio en la acumulación de calcio intracelular y de la generación de AMP cíclico e incrementaron la activación de la quinasa ERK 1/2. Conclusiones: Las células óseas secretan factores activadores de la proliferación y de vías de señalización que favorecen la progresión tumoral de células de cáncer de próstata, sugiriendo que la comunicación cruzada entre estos tipos celulares puede favorecer el desarrollo de nichos metástasicos de cáncer de próstata en el hueso

Objectives: To analyze in prostate tumor cells the effects caused by the secretome of bone cells on pro- liferation and on intracellular signaling pathways related to the progression of prostate cancer. Materials and methods: The effects of secreted factors present in conditioned media of pre-osteoblasts MC3T3-E1 and osteocytes MLO-Y4 on the proliferation of metastatic prostate adenocarcinoma cells PC-3 were characterized using trypan blue staining. The effects of media conditioned by MC3T3-E1 and MLO- Y4 cells on intracellular signaling molecules involved in the tumor progression of prostate adenocarcinoma cells PC-3 were observed by fluorescence techniques in living cells. The accumulation of intracellular calcium was studied using the fluorescent calcium indicator Fluo-4AM and the generation of cyclic AMP, and ERK 1/2 activation by Fluorescent Resonance Energy Transfer (FRET) using the EPAC and ERKNES biosensors, respectively. Results: The stimulation of PC-3 cells with conditioned media of pre-osteoblasts MC3T3-E1 and osteocytes MLO-Y4 induced an increase in PC-3 adenocarcinoma cell proliferation. Media conditioned by bone cells also caused a transient increase in intracellular calcium accumulation and generation of cyclic AMP and increased ERK 1/2 activation. Conclusions: Bone cells secrete proliferation-activating factors and signaling pathways that favor the tumor progression of prostate cancer cells, suggesting that cross-communication between these cell types may favor the development of metastatic niches of prostate cancer in the bone

Tibiotarsus bone characteristics and tibial dyschondroplasia incidence of broilers fed diets supplemented with leucine and valine.

Two experiments were conducted to study the effect of standardized ileal digestible (SID) leucine and valine levels on tibiotarsus bone characteristics and the incidence of tibial dyschondroplasia of broilers from day 1 to 21 (Experiment I) and day 21 to 42 post-hatch (Experiment II). Each experimental phase was evaluated independently. In both experiments, a total of 1,500 one-day-old Cobb 500 male broiler chickens were distributed in a completely randomized design 5 × 5 factorial arrangement for a total of 25 treatments. The SID leucine and valine levels were ranged from 10.0 to 19.6 g/kg, and 6.0 to 12.0 g/kg from day 1 to 21 post-hatch, respectively, while day 21 to 42 post-hatch ranged from 10.0 to 18.0 g leucine/kg, and 5.2 to 11.2 g valine/kg. Serum calcium and phosphorus, bone concentrations of calcium, phosphorus and ash, diameter and Seedor index of the tibiotarsus were not affected (p > .05) by the treatments at 21 or 42 days of age. There was an interaction (p ≤.06) between the SID levels of leucine and valine on tibiotarsus breaking strength at 21 days, but not at 42 days of age (p > .05). Tibiotarsus breaking strength was maximized in broilers from day 1 to 21 with the dietary levels of leucine and valine at 14.2 and 9.0 g/kg respectively. Dietary leucine levels reduced linearly (p < .05) the hypertrophic zone of tibiotarsus cartilage at 21 days of age. Therefore, leucine and valine supplementation interact positively on bone strength of broilers from day 1 to 21 post-hatch. Leucine can be a useful amino acid for reducing the hypertrophic cartilage zone in broilers from day 1 to 21, but not from day 21 to 42 post-hatch.