Influence of Single-Nucleotide Polymorphisms on Clinical Outcomes of Capecitabine-Based Chemotherapy in Colorectal Cancer Patients: A Systematic Review

The aim of this systematic review was to provide a comprehensive overview of the literature published in the last decade on the association of single-nucleotide polymorphisms in genes involved in the pharmacodynamic and pharmacokinetic pathways of capecitabine with treatment outcomes among colorectal cancer patients. A systematic search of the literature published in the last 10 years was carried out in two databases (Medline and Scopus) using keywords related to the objective. Quality assessment of the studies included was performed using an assessment tool derived from the Strengthening the Reporting of Genetic Association (STREGA) statement. Thirteen studies were included in this systematic review. Genes involved in bioactivation, metabolism, transport, mechanism of action of capecitabine, DNA repair, and folate cycle were associated with toxicity. Meanwhile, genes related to DNA repair were associated with therapy effectiveness. This systematic review reveals that several SNPs other than the four DPYD variants that are screened in clinical practice could have an impact on treatment outcomes. These findings suggest the identification of future predictive biomarkers of effectiveness and toxicity in colorectal cancer patients treated with capecitabine. However, the evidence is sparse and requires further validationCo-funded by ERDF funds (EU) from the Instituto de Salud Carlos III (PT13/0010/0039)

Tributación : Incentivos del régimen tributario de Admisión Temporal, establecido en la ley 382, Ley de Admisión Temporal para el perfeccionamiento Activo y de Facilitación de las Exportaciones, en la Republica de Nicaragua.

El presente documento hace referencia a Incentivos del Régimen Tributario de Admisión Temporal, establecido en la Ley 382, Ley de Admisión Temporal de Perfeccionamiento Activo y de Facilitación de las Exportaciones en la República de Nicaragua, en el cual se tiene como objetivo conocer la importancia y la aplicación de los incentivos del régimen tributario de Admisión Temporal, establecido en la Ley 382. La metodología implementada es analítica y descriptiva debido a que se realiza análisis de los incentivos del régimen de admisión temporal por medio de la Ley 382 y la aplicación de la misma mediante un caso práctico con la en el cual se logró demostrar uno de los beneficios que obtendría la empresa OYANKA S, A al estar bajo el régimen de admisión temporal. Además este régimen permite, el ingreso de las mercancías suspensas de derechos e impuestos y bajo ciertas condiciones con el fin de fomentar el crecimiento económico, la creación de empleos y posicionamiento en el mercado internacional., Para estar amparado bajo este Régimen Tributario se debe cumplir con los requisitos establecidos en esta Ley y su Reglamento partiendo del llenado del formato de solicitud de inscripción emitido por el CNPE y la aprobación de la misma, así mismo se requiere la previa autorización de la autoridad aduanera y la constitución de una garantía para asegurar el pago de los derechos e impuestos. Es necesario mencionar que los beneficios tributarios que son otorgados por medio de este Régimen de las exportaciones nicaragüenses en el mercado internacional, a través de dos modalidades: Suspensión previa de derechos e impuestos o la Devolución de los mismos

La concepción de la sexualidad en las personas con síndrome de Down, desde la mirada de los padres de familia: caso de estudio en la Fundación Cultural Edgar Palacios en el año lectivo 2019-2020

La sexualidad en las personas con discapacidad no ha sido tomada en cuenta por parte de la sociedad ecuatoriana, por lo cual es vista como un tema tabú. Los padres de familia de los jóvenes con discapacidad no piensas que su hijo/a pueda atravesar por esta transición a la adultez. El propósito de este trabajo es conocer acerca de la concepción de la sexualidad de las personas con síndrome de Down, desde la mirada de los padres de familia en la Fundación Cultural Edgar Palacios durante el año escolar 2019-2020, mediante la investigación cualitativa, documental y de campo, las cuales consistieron en entrevistas a profundidad a padres de familia, siendo el enfoque descriptivo indispensable en el estudio. Dentro del marco social ecuatoriano la sexualidad de las personas con síndrome de Down no es tomada en cuenta, no tiene relevancia ya que por su condición son infantilizadas y por ende no se considera que exista desarrollo en su sexualidad. El resultado principal acerca de la sexualidad de las personas con síndrome de Down, es que los padres tienden a creer que sus hijos no van a atravesar por un desarrollo común al igual que los demás jóvenes de su edad, esta creencia se debe al desconocimiento que tienen sobre el tema.Sexuality in people with disabilities has not been taken into account by Ecuadorian society, which is why it is seen as a taboo subject. Parents of youth with disabilities do not think that their child can go through this transition to adulthood. The purpose of this work is to learn about the conception of sexuality of people with Down syndrome, from the perspective of parents at the Edgar Palacios Cultural Foundation during the 2019-2020 school year, through qualitative research, documentary and field, which consisted of in-depth interviews with parents, being the essential descriptive approach in the study. Within the Ecuadorian social framework, the sexuality of people with Down syndrome is not taken into account, it has no relevance since due to their condition they are infantilized and therefore it is not considered that there is development in their sexuality. The main result about the sexuality of people with Down syndrome is that parents tend to believe that their children will not go through a common development like other young people their age, this belief is due to ignorance that have on the subject

Comparison between MAC and PIAR

Teniendo en cuenta que hay actores sociales individuales y colectivos, que, según su incidencia, ya sea positiva o negativa, impacta en la estructura del individuo en sociedad o en la sociedad frente al individuo. La dinámica social mediara el marco de desarrollo del actor de tomadores y ejecutores frente a la realidad social, quienes a su vez hacen parte de este entorno y se movilizan desde una reglas, patrones y dinámicas propias de su entorno; ya sea, familia, profesionales (instituciones educativas, cuerpo docente, instituciones de protección, defensoría de familia, entidades de salud), teoría, lineamiento y leyes.Magíster en Educación Inclusiva e InterculturalMaestríaTaking into account that there are individual and collective social actors, which, according to their incidence, whether positive or negative, impact on the structure of the individual in society or on society in relation to the individual. The social dynamics mediate the development framework of the actor's framework of decision makers and executors in front of the social reality, who in turn are part of this environment and are mobilized from rules, patterns and dynamics of their own environment, whether family, professionals (educational institutions, teaching staff, protection institutions, family ombudsman, health entities), theory, guidelines and laws

Impact of Functional Polymorphisms on Drug Survival of Biological Therapies in Patients with Moderate-to-Severe Psoriasis

Biological therapies (BTs) indicated for psoriasis are highly effective; however, not all patients obtain good results, and loss of effectiveness is the main reason for switching. Genetic factors may be involved. The objective of this study was to evaluate the influence of single-nucleotide polymorphisms (SNPs) on the drug survival of tumor necrosis factor inhibitors (anti-TNF) medications and ustekinumab (UTK) in patients diagnosed with moderate-to-severe psoriasis. We conducted an ambispective observational cohort study that included 379 lines of treatment with anti-TNF (n = 247) and UTK (132) in 206 white patients from southern Spain and Italy. The genotyping of the 29 functional SNPs was carried out using real-time polymerase chain reaction (PCR) with TaqMan probes. Drug survival was evaluated with Cox regression and Kaplan-Meier curves. The multivariate analysis showed that the HLA-C rs12191877-T (hazard ratio [HR] = 0.560; 95% CI = 0.40-0.78; p = 0.0006) and TNF-1031 (rs1799964-C) (HR = 0.707; 95% CI = 0.50-0.99; p = 0.048) polymorphisms are associated with anti-TNF drug survival, while TLR5 rs5744174-G (HR = 0.589; 95% CI = 0.37-0.92; p = 0.02), CD84 rs6427528-GG (HR = 0.557; 95% CI = 0.35-0.88; p = 0.013) and PDE3A rs11045392-T together with SLCO1C1 rs3794271-T (HR = 0.508; 95% CI = 0.32-0.79; p = 0.002) are related to UTK survival. The limitations are the sample size and the clustering of anti-TNF drugs; we used a homogeneous cohort of patients from 2 hospitals only. In conclusion, SNPs in the HLA-C, TNF, TLR5, CD84, PDE3A, and SLCO1C1 genes may be useful as biomarkers of drug survival of BTs indicated for psoriasis, making it possible to implement personalized medicine that will reduce financial healthcare costs, facilitate medical decision-making and improve patient quality of life. However, further pharmacogenetic studies need to be conducted to confirm these associations.University of Granada and the Fundación de Investigación Biosanitaria de Andalucía Oriental (FIBAO)Virgen de las Nieves University Hospital Biobank was supported by grants co-funded by ERDF funds (EU) from the Instituto de Salud Carlos III (PT13/0010/0039)

Biomaterials for bone regeneration

Objective: This article reviews the literature on biomaterials used for bone regeneration. Material and method: A total of seventeen bibliographic sources were found using the MEDLINE database and to avoid the variability of the search terms the thesaurus Mesh was used. Results: These materials act essentially due to their osteoconductive ability, although their osteoinductive capacity is being improved with the use of growth factors. As to their effectiveness, many differences exist between them and some even affect bone regeneration negatively. Conclusions: Biomaterials used for bone regeneration are valid when the correct material is used. As yet the osteogenic capacity of autogenous bone has not been equalled by biomaterials. Tissue engineering has caused great interest because of its many possibilities, although more studies are necessary in order to achieve the ambitious expectations when it comes to tissue or organ regeneration in the human bod

Influence of Genetic Polymorphisms on Response to Biologics in Moderate-to-Severe Psoriasis

This work was partly supported by a contract for Cristina Membrive Jimenez from the University of Granada and the Fundacion de Investigacion Biosanitaria de Andalucia Oriental (FIBAO). The Virgen de las Nieves University Hospital Biobank was supported by grants co-funded by ERDF funds (EU) from the Instituto de Salud Carlos III (PT13/0010/0039).The results of this research are part of the doctoral thesis that will be presented by Cristina Membrive Jiménez at the University of Granada as part of the doctoral studies in “Pharmacy”.Psoriasis is a chronic inflammatory skin pathology of autoimmune origin and unknown etiology. There are various therapies for treating it, including a wide range of biopharmaceuticals indicated in moderate-to-severe psoriasis. Depending on their therapeutic target, they are classified as tumor necrosis factor inhibitors (anti-TNF) or cytokine inhibitors (interleukin-12, 23, and 17 antagonists). Although they have proved effective and safe, in clinical practice, many patients show a short- and long-term suboptimal response and even varying degrees of toxicity. This variability in response may be influenced by genetic factors, such as polymorphisms in the genes involved in the pathological environment, metabolism or mechanism of action of the drug that could affect the effectiveness and toxicity of biological therapies. This review assesses pharmacogenetic studies of the impact of genetic factors on response to biopharmaceuticals and toxicity in patients diagnosed with moderate-to-severe psoriasis. The results suggest that polymorphisms detected in the HLA genes, in genes that encode cytokines (TNF, IL genes, TNFAIP3), transporters (PDE3A-SLCO1C1, SLC12A8), receptors (TNFRSF1B, CD84, FCGR2A and FCGR3A, IL17RA, IL23R, TLR genes, PGLYRP4) and associated proteins (TNFAIP3, LY96, TIRAP, FBXL19), as well as other genes implicated in the pathogenesis of psoriasis (CDKAL1, CARD14, PTTG1, MAP3K1, ZNF816A, GBP6, CTNNA2, HTR2A, CTLA4, TAP1) can be used in the future as predictive markers of treatment response and/or toxicity with biological therapies in patients diagnosed with moderate-to-severe psoriasis, tailoring treatment to the individual patient.University of GranadaFundacion de Investigacion Biosanitaria de Andalucia Oriental (FIBAO)ERDF funds (EU) from the Instituto de Salud Carlos III PT13/0010/003

Risk of contagion of SARS-CoV-2 among otorhinolaryngologists in Spain during the 'Two waves'.

Introduction The aim of our study was to obtain data about the contagion rate among Otolaryngologists in Spanish ENT Departments and about the clinical outcomes in positive otolaryngologists. As a secondary objective, we aim to assess the rate of contagion in the first and the second Covid-19 wave in Spain among Otorhinolaryngologists and the regional distribution by ENT-Departments. Methods Study design and population: This is a prospective observational study in a cohort of 975 Otolaryngologists from 87 ENT Departments conducted from March 25 to November 17 in our collaborative group, COVID ORL ESP. COVID-19 polymerase chain reaction (PCR) was the diagnostic standard. Hospitalization and/or intensive care admission and mortality was recorded as non-identified data. Results Data collected from 975 otolaryngologist from 87 Departments resulted in 157 (16.5%) otolaryngologists testing positive for SARS-CoV-19 by RT-PCR. Important geographic differences in contagion are reported. A total of 136 (86.6%) otolaryngologists were tested positive during the first wave and 21 (13.3%) during the second wave. At the last cut-off point of the study only 30/87 ENT Departments (34.5%) remained COVID19-free and 5 Departments reported more than 50% staff members testing positive. The majority of positive tested otolaryngologists (126/157; 80.2%) had only mild or no symptoms, 17 developed moderate symptoms (10.8%) and 3 had pneumonia not requiring hospitalization (2%). Five colleagues were admitted at hospital, 4 required ICU (2.5%) and 2 colleges died from COVID-19. Conclusions During the first wave of the SARS-CoV-19 pandemic otolaryngologists in Spain have been overall the group suffering the highest rate of contagion, particularly during the first month. Subsequently, the Spanish Ministry of Health should include otorhinolaryngologists as a high-risk group in airborne pandemics

Hypoxia-Inducible Factor-1 Alpha Expression Is Predictive of Pathological Complete Response in Patients with Breast Cancer Receiving Neoadjuvant Chemotherapy

Supplementary Materials The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cancers14215393/s1, Table S1: Relation between HIF-1α expression and pAKT and pMAPK; Table S2: Logistic regression model as a predictive factor of response to treatment.To demonstrate the value of hypoxia-inducible factor-1α (HIF-1α) in predicting response in patients with breast cancer receiving standard neoadjuvant chemotherapy (NAC). Methods: Ninety-five women enrolled in two prospective studies underwent biopsies for the histopathological diagnosis of breast carcinoma before receiving NAC, based on anthracyclines and taxanes. For expression of HIF-1α, EGFR, pAKT and pMAPK, tumor samples were analyzed by immunohistochemistry in tissues microarrays. Standard statistical methods (Pearson chi-square test, Fisher exact test, Kruskal–Wallis test, Mann–Whitney test and Kaplan–Meier method) were used to study the association of HIF-1α with tumor response, survival and other clinicopathologic variables/biomarkers. Results: HIF-1α expression was positive in 35 (39.7%) cases and was significantly associated to complete pathological response (pCR) (p = 0.014). HIF-1α expression was correlated positively with tumor grade (p = 0.015) and Ki-67 expression (p = 0.001) and negativity with progesterone receptors (PR) (p = 0.04) and luminal A phenotype expression (p = 0.005). No correlation was found between HIF-1α expression and EGFR, pAKT and pMAPK. In terms of survival, HIF-1α expression was associated with a significantly shorter disease-free survival (p = 0.013), being identified as an independent prognostic factor in multivariate analysis. Conclusions: Overexpression of HIF-1α is a predictor of pCR and shorter DFS; it would be valuable to confirm these results in prospective studies