Luces y sombras del cribado del cáncer de próstata.

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Low peripheral blood chemokine (C-C motif) ligand 5 and tumor necrosis factor α gene expression is associated with unfavorable progression of respiratory syncytial virus bronchiolitis in infants

Objectives: We aimed to analyze whether the expression of inflammatory and antiviral genes in respiratory syncytial virus (RSV)-infected infants' peripheral blood is associated with bronchiolitis progression. Methods: We conducted a prospective study on 117 infants between 2015 and 2023. The expression levels of nine genes were quantified by quantitative polymerase chain reaction. Infants were classified according to their clinical evolution during hospital admission: (i) non-progression (n = 74), when the RSV bronchiolitis severity remained stable or improved; (ii) unfavorable progression (n = 43), when the RSV bronchiolitis severity increased. The association analysis was performed by logistic regression, adjusted by age, gender, prematurity, and RSV bronchiolitis severity in the emergency room. Results: Infants were 57.3% male, and the median age of the study population was 61 days. Thirty-five infants (30.7%) were admitted to the intensive care unit after hospital admission. Univariate logistic models showed that tumor necrosis factor (TNFα) and chemokine (C-C motif) ligand (CCL5) gene expression at baseline were inversely associated with unfavorable progression, which was confirmed by multivariate analyses: TNFα (adjusted odds ratio = 0.8 [95% confidence interval = 0.64-0.99], P-value = 0.038) and CCL5 (adjusted odds ratio = 0.76 [95% confidence interval = 0.62-0.93], P-value = 0.007). Conclusions: An inadequate immune response to RSV, characterized by reduced gene expression levels of CCL5 and TNFα in peripheral blood, was associated with an unfavorable progression of RSV bronchiolitis.The study was funded by the CIBER -Consorcio Centro de Investigación Biomédica en Red- (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU (grant # CB21/13/00044 to SR)S

MTHFR rs1801133 Polymorphism Is Associated With Liver Fibrosis Progression in Chronic Hepatitis C: A Retrospective Study.

Background: The MTHFR (methylenetetrahydrofolate reductase) rs1801133 polymorphism leads to higher circulating levels of homocysteine, which is related to several liver diseases. We aimed to evaluate the relationship between MTHFR rs1801133 polymorphism and liver fibrosis progression in HCV-infected patients. Methods: We conducted a preliminary retrospective cohort study in 208 non-cirrhotic HCV-infected patients. These subjects had at least two liver stiffness measurements (LSM), which were assessed using transient elastography, and no patient had cirrhosis at baseline. We analyzed the association between MTHFR rs1801133 and outcome variables using Generalized Linear Models. Results: HCV-infected patients were 47 years old, around 54% were males, a low frequency of high alcohol intake (13.5%) or prior use of intravenous drugs (10.1%). A total of 26 patients developed cirrhosis (LSM1 ≥ 12.5) during a median follow-up of 46.6 months. The presence of the rs1801133 C allele showed an inverse association with the LSM2/LSM1 ratio (adjusted AMR = 0.90; 95%CI = 0.83-0.98; p = 0.020) and the cirrhosis progression (adjusted OR = 0.43; 95%CI = 0.19-0.95; p = 0.038). Besides, rs1801133 CT/CC genotype had an inverse association with the LSM2/LSM1 ratio (adjusted AMR = 0.80; 95%CI = 0.68-0.95; p = 0.009) and the cirrhosis progression (adjusted OR= 0.21; 95%CI = 0.06-0.74; p = 0.015). Conclusions:MTHFR rs1801133 C allele carriers presented a diminished risk of liver fibrosis progression and development of cirrhosis than rs1801133 T allele carriers. This statement supports the hypothesis that MTHFR rs1801133 polymorphism appears to play a crucial role in chronic hepatitis C immunopathogenesis.This work has been supported by grants given by Instituto de Salud Carlos III (ISCIII) (grant # PI17CIII/00003 to SR). MJ-S and AF-R are supported by Instituto de Salud Carlos III (grant # CP17CIII/00007 and CP14CIII/00010, respectively).S

PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study.

Corrigendum to "PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study" [Biomed. Pharmacother. 159 (2023) 114220]. Biomed Pharmacother. 2023 Apr 27;114803. doi: 10.1016/j.biopha.2023.114803. PMID: 37120412.Background: Patients with advanced cirrhosis are at high risk of developing clinically significant portal hypertension (CSPH). We analyzed the gene expression profile of peripheral blood mononuclear cells (PBMCs) from HIV/HCV coinfected patients to identify a gene expression signature of advanced cirrhosis with high risk for CSPH. Methods: We conducted a cross-sectional study on 68 patients. Liver stiffness measurement (LSM) was used to stratify patients into < 12.5 kPa (no cirrhosis, n = 19), 12.5 - 24.9 kPa (cirrhosis, n = 20), and ≥ 25 kPa (advanced cirrhosis with high risk for CSPH, n = 29). Besides, we further evaluated LSM < 25 kPa (n = 39) vs. ≥ 25 kPa (n = 29). Total RNA was extracted from PBMCs, and poly(A) RNA sequencing was performed. Two significant differentially expressed (SDE) transcripts were validated by quantitative PCR in a different cohort (n = 46). Results: We found 60 SDE transcripts between patients with LSM < 12.5 kPa and ≥ 25 kPa. Partial least squares discriminant analysis showed that those 60 SDE transcripts collectively discriminated LSM ≥ 25 kPa, with an area under the receiver operating characteristic curve (AUROC) of 0.84. Eight genes had an AUROC ≥ 0.75 for LSM ≥ 25 kPa: five were positively associated with LSM values (SCAMP1, ABHD17B, GPR146, GTF2A1, and TMEM64), while three were inversely associated (ZFHX2-AS1, MDK, and STAG3L2). We validated the two SDE transcripts with the highest discrimination capacity in a different cohort, finding significant differences between < 25 kPa and ≥ 25 kPa (MDK (p = 0.006) and STAG3L2 (p = 0.021)). Conclusions: A gene expression signature of 60 transcripts was associated with advanced cirrhosis with high risk for CSPH in HIV/HCV coinfected patients.This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers CP17CIII/00007 and PI18CIII/00028 to MAJS, PI17/00657 and PI20/00474 to JB, PI17/00903 and PI20/00507 to JGG, PI18CIII/00020 to AFR, and PI17CIII/00003 and PI20CIII/00004 to SR) and Ministerio de Ciencia e Innovación (AEI, PID2021-126781OB-I00 to AFR). The study was also funded by the CIBER -Consorcio Centro de Investigación Biomédica en Red- (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU (CB21/13/00044).S

TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients

TRPM5 (transient receptor potential cation channel subfamily M member 5) rs886277 polymorphism has been related to liver cirrhosis from different etiologies. The present study investigates the association of TRPM5 rs886277 polymorphism with liver fibrosis progression and cirrhosis development in chronic hepatitis C (CHC) patients. We conducted a retrospective study of 208 non-cirrhotic patients with CHC, who had at least two liver stiffness measurements (LSM) with a separation of 12 months (baseline LSM (LSM1) and the last LSM (LSM2)). Two outcome variables were considered: (1) LSM2/LSM1 ratio; (2) cirrhosis progression (F4; LSM ≥ 12.5 kPa). DNA genotyping was done at the CeGen using a MassARRAY platform. The follow-up time was similar irrespective of the rs886277 genotype (46.4 months in TT genotype, 46.4 months in CT genotype, and 49.2 months in CC genotype; p = 0.649). The highest LSM increases were found in patients with CC genotype compared with TT and CT genotypes (p = 0.044 and p = 0.038, respectively). The cirrhosis progression was higher in patients with CC genotype than TT genotype (p = 0.033). Thus, the rs886277 C allele was associated with higher cirrhosis progression (adjusted odds ratio (aOR) = 2.64; p = 0.014). Moreover, rs886277 CC genotype was also related to higher values of LSM2/LSM1 ratio (adjusted arithmetic mean ratio a(AMR) = 1.31; p = 0.001) and cirrhosis progression (aOR = 4.33; p = 0.027). TRPM5 rs886277 polymorphism was associated with liver fibrosis progression and cirrhosis development among hepatitis C virus (HCV)-infected patients. Specifically, the rs886277 C allele and CC genotype were risk factors for advancing liver fibrosis and cirrhosis compared to the rs886277 T allele and CT/TT genotype, respectively.This study is supported by grants from Instituto de Salud Carlos III (ISCIII) (grant # PI20CIII/00004 to S.R.). M.A.J.-S. and A.F.-R. are supported by “Instituto de Salud Carlos III” (grant # CP17CIII/00007 and CP14CIII/00010, respectively).S

Reduced antiviral gene expression and elevated CXCL8 expression in peripheral blood are associated with severe hypoxemia in RSV-infected children

The pathology of respiratory syncytial virus (RSV) infection remains unclear. An unbalanced immune response to RSV infection can lead to immunopathology, causing airway damage and impaired exchange of oxygen and carbon dioxide between the air and the bloodstream. We aimed to evaluate the association of the expression of inflammatory and antiviral genes in peripheral blood with severe hypoxemia in children with RSV infection seen in the hospital emergency room. We conducted a cross-sectional study on 121 RSV-infected children seen in hospital emergency rooms between 2015 and 2023. Total RNA was extracted from whole blood samples, and gene expression (IL-6, TNFα, CXCL8, ISG15, IFIT1, RIGI, IFNβ, CCL5, and CXCL10) was quantified using quantitative RT-PCR. The outcome variable was having severe hypoxemia (SpO2 ≤ 90%). The association analysis was performed using a volcano plot, adjusted logistic regression, and orthogonal partial least squares discriminant analysis (OPLS-DA). We found that 26 of 121 children had severe hypoxemia (SpO2 ≤ 90%). CXCL8 was overexpressed [fold changes (FC) &gt; 2; q-value &lt; 0.05], and ISG15, IFIT1, RIGI, IFNβ, CCL5, and CXCL10 were underexpressed (FC &lt;0.5; q-value &lt;0.05) in children with severe hypoxemia. These associations were ratified using adjusted logistic regression. The OPLS-DA showed that the gene expressions of CXCL8, ISG15, IFIT1, RIGI, and CXCL10 had values of variable importance in projection (VIP) ≥1, being the most relevant features. In conclusion, an imbalance favoring inflammation over antiviral defense may contribute to the pathogenesis of severe hypoxemia in RSV-infected children. These findings provide valuable insights into the pathology of RSV infection

Metabolomic changes after DAAs therapy are related to the improvement of cirrhosis and inflammation in HIV/HCV-coinfected patients

Background: A better understanding of the evolution of cirrhosis after hepatitis C virus (HCV) clearance is essential since the reversal of liver injury may not happen. We aimed to assess the evolution of plasma metabolites after direct-acting antivirals (DAAs) therapy and their association with liver disease scores in HIV/HCV-coinfected patients with advanced HCV-related cirrhosis. Methods: We performed a prospective study in 49 cirrhotic patients who started DAAs therapy. Data and samples were collected at baseline and 36 weeks after SVR. Metabolomics analysis was carried out using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. Inflammation-related biomarkers were analyzed using ProcartaPlex Immunoassays. Results: At 36 weeks after SVR, patients experienced significant decrease in taurocholic acid, 2,3-butanediol, and LPC(18:0); while several phosphatidylcholines (LPC(16:1), LPC(18:1), LPC(20:4), and PC(16:0/9:0(CHO))/PC(16:0/9:0(COH)), 2-keto-n-caproic acid/2-keto-isocaproic acid and N-methyl alanine increased, compared to baseline. The plasma decrease in taurocholic acid was associated with a reduction in Child-Turcotte-Pugh (CTP) (AMR=3.39; q-value=0.006) and liver stiffness measurement (LSM) (AMR=1.06; q-value<0.001), the plasma increase in LPC(20:4) was related to a reduction in LSM (AMR=0.98; q-value=0.027), and the rise of plasma 2-keto-n-caproic acid/2-keto-isocaproic acid was associated with a reduction in CTP (AMR=0.35; q-value=0.004). Finally, plasma changes in taurocholic acid were directly associated with inflammation-related biomarkers, while changes in LPC(20:4) were inversely associated. Conclusions: Plasma metabolomic profile changed after HCV clearance with all oral-DAAs in HIV/HCV-coinfected with advanced HCV-related cirrhosis. Changes in plasma levels of LPC (20: 4), 2-keto-n-caproic acid/2-keto-isocaproic acid, and taurocholic acid were related to improvements in cirrhosis scores and inflammatory status of patients.This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers CP17CIII/00007 (MPY407/18) and PI18CIII/00028 (MPY385/18) to MAJS, PI14/01094, PI17/00657, and PI20/00474 to JB, PI14/01581, PI17/00903 and PI20/00507 to JGG, and PI14CIII/00011, PI17CIII/00003, and PI20CIII/00004 to SR) and Ministerio de Sanidad, Servicios Sociales e Igualdad (grant number EC11–241). The study was also funded by the Spanish AIDS Research Network (RD16/0025/0017, RD16/0025/0018 and RD16CIII/0002/0002) and Centro de Investigación Biomédica en Red (CIBER) en Enfermedades Infecciosas (CB21/13/00044 and CB21/13/00039). MAJS is a Miguel Servet researcher supported and funded by ISCIII (grant number: CP17CIII/00007). JB is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS), Refs INT16/00100. CB and DR acknowledge funding from the Ministerio de Ciencia, Innovación y Universidades (RTI2018–095166-B-I00).S

Relative telomere length impact on mortality of COVID-19: Sex differences

Increasing age is associated with severity and higher mortality of COVID-19. Telomere shortening is associated with higher risk of infections and may be used to identify those patients who are more likely to die. We evaluated the association between relative telomere length (RTL) and COVID-19 mortality. RTL was measured in patients hospitalized because of COVID-19. We used Kaplan-Meier method to analyze survival probabilities, and Cox regression to investigate the association between RTL and mortality (30 and 90 days). Six hundred and eight patients were included in the analysis (mean age =72.5 years, 41.1% women, and 53.8% Caucasic). During the study period, 75 people died from COVID-19 and 533 survived. Lower RTL was associated with a higher risk of death in women either at 30 (adjusted hazard ratio [HR] (aHR) = 3.33; 95% confidence interval [CI] = 1.05-10.00; p = 0.040) and at 90 days (aHR = 3.57; 95%CI = 1.23-11.11; p = 0.019). Lower RTL was associated with a higher risk of dying of COVID-19 in women. This finding suggests that RTL has an essential role in the prognosis of this subset of the population.This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant number COV20/1144 [MPY224/20] to AFR/MAJS) and Fundación Universidad Alfonso X el Sabio (FUAX) – Santander (1.013.005). MAJS is Miguel Servet researcher supported and funded by ISCIII (grant number: CP17CIII/00007). The study was also supported by the Centro de Investigación Biomédica en Red (CIBER) en Enfermedades Infecciosas (CB21/13/00044). We also acknowledge the Spanish Coalition to Unlock Research on Host Genetics on COVID‐19 (SCOURGE).S

Estrategias docentes en asignaturas del máster en Ingeniería Química: Ingeniería de Procesos

El título de Máster de Ingeniería Química: Ingeniería de Procesos complementa los estudios del Grado en Ingeniería Química, constituyendo una profundización y extensión de los conocimientos adquiridos en el mismo, así como la adquisición de una formación adecuada para la continuación de estudios de doctorado en el área de la Ingeniería Química. La existencia de estudios avanzados de Ingeniería Química como continuación o unidos a los estudios de primer nivel universitario es prácticamente general en universidades de todos los países, aunque de diferentes modos en función de la configuración de sus estudios propios. Los estudios de Ingeniería Química tienen larga tradición en la Universidad Complutense, que ha sido un referente a nivel nacional para la implantación de nuevos planes de estudio en esta disciplina. En 1944, se establecieron los estudios del Doctorado en Química Industrial, que incluían asignaturas de especialización en Ingeniería Química. En 1960, se inicia la especialidad de Química Industrial en los dos últimos cursos de la Licenciatura en Ciencias Químicas, cuyo plan de estudios se modifica posteriormente en 1970. En 1992 comienza a impartirse el título de Ingeniero Químico que se ha mantenido hasta la implantación del Grado en Ingeniería Química conforme a las directrices del EEES. Los estudios de Posgrado a nivel de Máster se establecen en 2006 al comenzar los programas oficiales de Postgrado, primero con el Máster de Ingeniería de Procesos Industriales, que ha mantenido una gran aceptación durante todos los cursos en los que se ha impartido. El Programa Oficial de Postgrado de Ingeniería Química obtuvo la Mención de Calidad en el año 2006. El presente Máster sustituye a este primer curso de postgrado, adaptándose al EEES. La Universidad Complutense debe tener una estrategia de futuro por los postgrados, por lo que se deben introducir mejoras en la docencia de los mismos que hagan más atractivo los Másteres impartidos. La consecución de este objetivo pasa por el diseño y aplicación de metodologías de enseñanza-aprendizaje lo suficientemente flexibles para adaptarse a las circunstancias personales del alumnado. En este contexto, las Tecnologías de la Información y la Comunicación posibilitan una oferta académica flexible, así como la diversificación de metodologías docentes. La utilización de los espacios virtuales cobra una especial relevancia en los estudios de Máster dada la peculiaridad del alumnado de este nivel, como es su formación superior o la frecuente simultaneidad de sus estudios con la actividad profesional. El desarrollo de actividades que promuevan la participación y, como consecuencia, el mayor protagonismo y autonomía del estudiante en el aprendizaje, justifica este proyecto de innovación educativa. En este contexto, tras dos cursos académicos desde que se inició el Máster en Ingeniería Química: Ingeniería de Procesos, en la Facultad de Ciencias Químicas, se han detectado algunas deficiencias, como son la insuficiente participación activa del alumno en la resolución de casos en el aula, la deficiente capacidad creativa en la resolución de casos prácticos y por último, una insuficiente interacción entre los alumnos en el análisis de casos prácticos. Las alternativas que se proponen en este proyecto son mejorar la eficiencia en los procesos de adquisición de los resultados de aprendizaje por parte de los estudiantes, con especial atención a la incorporación de metodologías activas para el aprendizaje; potenciar que los alumnos sean activos en el proceso de aprendizaje autodirigido, explotando las posibilidades de las redes y las Tecnologías del Aprendizaje y Conocimiento como sistemas de acceso a los recursos; y por último, desarrollar repositorios de prácticas, recursos docentes, y actividades, que faciliten la experimentación así como el aprendizaje autónomo

Immunological and senescence biomarker profiles in patients after spontaneous clearance of hepatitis C virus: gender implications for long-term health risk

Background: About 25% of patients with acute hepatitis C virus (HCV) infection show spontaneous clearance within the first six months of infection but may remain at risk of inflammaging, aging, and liver and non-liver disease complications. This study evaluated the differences in the plasma levels of immune checkpoints (ICs) and senescence-associated secretory phenotype (SASP) biomarkers between patients who had spontaneously eliminated HCV infection (SC group) and individuals without evidence of HCV infection (C group). Methods: We performed a multicenter retrospective study of 56 individuals: 32 in the SC and 24 in the C groups. ICs and SASP proteins were analyzed using a Luminex 200TM analyzer. The statistical analysis used Generalized Linear Models with gamma distribution (log-link) adjusted by significant variables and sex. Results: 13 ICs (BTLA, CD137(4-1BB), CD27, CD28, CD80, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, and TIM-3) and 13 SASP proteins (EGF, Eotaxin, IL-1alpha, IL-1RA, IL-8, IL-13, IL-18, IP-10, SDF-1alpha, HGF, beta-NGF, PLGF-1, and SCF) were significantly higher in SC group after approximately more than two years of HCV clearance. After stratifying by sex, differences remained significant for males, which showed higher levels for 13 ICs and 4 SASP proteins in SC. While only PD-L2 was significantly higher in SC women, and no differences in SASP were found. Conclusions: Higher plasma levels of different IC and SASP proteins were found in individuals after more than two years of HCV clearance, mainly in men. Alterations in these molecules might be associated with an increased risk of developing liver and non-hepatic diseases.This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant number CP14/0010) to AFR), Fundación Universidad Alfonso X el Sabio (FUAX) – Santander (grant number 1.010.932 to AFR) and by PID2021–126781OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. The study was also funded by the CIBER -Consorcio Centro de Investigación Biomédica en Red- (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next‑GenerationEU (CB21/13/00044, CB21/13/00118, and GVC16/EHD/4). M.A.J.-S. is Miguel Servet researcher supported and funded by ISCIII (grant numbers CP17CIII/00007). RME is Juan de la Cierva researcher supported and fnanced by MICINN of Spain (FJC2020-042865-I).S