Implementation of an extended ZINB model in the study of low levels of natural gastrointestinal nematode infections in adult sheep

Background: In this study, two traits related with resistance to gastrointestinal nematodes (GIN) were measured in 529 adult sheep: faecal egg count (FEC) and activity of immunoglobulin A in plasma (IgA). In dry years, FEC can be very low in semi-extensive systems, such as the one studied here, which makes identifying animals that are resistant or susceptible to infection a difficult task. A zero inflated negative binomial model (ZINB) model was used to calculate the extent of zero inflation for FEC; the model was extended to include information from the IgA responses. Results: In this dataset, 64 % of animals had zero FEC while the ZINB model suggested that 38 % of sheep had not been recently infected with GIN. Therefore 26 % of sheep were predicted to be infected animals with egg counts that were zero or below the detection limit and likely to be relatively resistant to nematode infection. IgA activities of all animals were then used to decide which of the sheep with zero egg counts had been exposed and which sheep had not been recently exposed. Animals with zero FEC and high IgA activity were considered resistant while animals with zero FEC and low IgA activity were considered as not recently infected. For the animals considered as exposed to the infection, the correlations among the studied traits were estimated, and the influence of these traits on the discrimination between unexposed and infected animals was assessed. Conclusions: The model presented here improved the detection of infected animals with zero FEC. The correlations calculated here will be useful in the development of a reliable index of GIN resistance that could be of assistance for the study of host resistance in studies based on natural infection, especially in adult sheep, and also the design of breeding programs aimed at increasing resistance to parasites

Factors that control the geochemical evolution of hydrothermal systems of alkaline water in granites in Central Pyrenees (Spain)

La evolución geoquímica de las soluciones de los sistemas hidrotermales de Caldas de Boí, Artiés, Tredós y Les, situados en el Pirineo Central (Spain), muestra diferencias reflejadas en la concentración de sólidos disueltos y en la presencia de una situación de equilibrio o desequilibrio en profundidad de las soluciones respecto a la albita. La datación (14C) de las aguas pertenecientes a los distintos sistemas hidrotermales ha puesto de manifiesto que el tiempo de residencia no es el factor de control determinante de las diferencias existentes en el grado de evolución geoquímica alcanzado por las mismas, teniendo que contemplarse otro tipo de factores relacionados con la cinética de disolución de los minerales, como responsables de estas diferencias. El análisis de la influencia de los principales factores que controlan la tasa de disolución de los minerales y, más en concreto, de los feldespatos, muestra como las diferencias de temperatura de las soluciones en profundidad son capaces de justificar el distinto grado de evolución geoquímica, incluso en soluciones con tiempos de residencia muy similares

ABCB1 Genetic Variants as Predictors of Irinotecan-Induced Severe Gastrointestinal Toxicity in Metastatic Colorectal Cancer Patients

Irinotecan is widely used in the treatment of metastatic colorectal cancer (mCRC) despite its severe toxicities. Toxicity is often associated with the UGT1A1*28/*28 genotype. An explanation for idiopathic toxicity beyond the UGT1A1 biomarker, however, remains a major concern for clinicians. One of the main irinotecan transporters is P-glycoprotein (P-gp), which is a hepatic efflux pump encoded by ABCB1. P-gp is involved in the biliary excretion of irinotecan and its active metabolite SN-38. We aimed to assess whether functional variants in ABCB1 also contribute to identifying patients at risk of toxicity. A cohort of 308 mCRC patients treated with irinotecan-based regimens were genotyped for polymorphisms in ABCB1 (rs1128503, rs2032582, and rs1045642). The effect of these variants and their haplotypes on irinotecan-induced severe toxicity (diarrhea, neutropenia, asthenia, nausea, and mucositis) was assessed. After adjusting for the relevant clinical and pathological parameters in the multivariate analysis, we found rs1128503 was significantly associated with severe diarrhea and mucositis (P=0.014 and P=0.002, respectively). Additionally, rs2032582 was associated with severe mucositis (P<0.001). Our results show that rs1128503 genotyping could help to predict severe gastrointestinal toxicity induced by irinotecan

A pharmacogenetic intervention for the improvement of the safety profile of antipsychotic treatments

Antipsychotic drugs fail to achieve adequate response in 30-50% of treated patients and about 50% of them develop severe and lasting side effects. Treatment failure results in poorer prognosis with devastating repercussions for the patients, carers and broader society. Our study evaluated the clinical benefits of a pharmacogenetic intervention for the personalisation of antipsychotic treatment. Pharmacogenetic information in key CYP polymorphisms was used to adjust clinical doses in a group of patients who started or switched treatment with antipsychotic drugs (PharmG+, N = 123), and their results were compared with those of a group of patients treated following existing clinical guides (PharmG−, N = 167). There was no evidence of significant differences in side effects between the two arms. Although patients who had their antipsychotic dose adjusted according to CYPs polymorphisms (PharmG+) had a bigger reduction in side effects than those treated as usual (PharmG−), the difference was not statistically significant (p > 0.05 for all comparisons). However, PharmG+ patients treated with CYP2D6 substrates that were carriers of CYP2D6 UMs or PMs variants showed a significantly higher improvement in global, psychic and other UKU side effects than PharmG− patients (p = 0.02, p = 0.05 and p = 0.01, respectively). PharmG+ clozapine treated patients with CYP1A2 or CYP2C19 UM and PMs variants also showed higher reductions in UKU scores than PharmG− clozapine patients in general. However, those differences were not statistically significant. Pharmacogenetic interventions may improve the safety of antipsychotic treatments by reducing associated side effects. This intervention may be particularly useful when considering treatment with antipsychotics with one major metabolic pathway, and therefore more susceptible to be affected by functional variants of CYP enzymes

Serotonergic Polymorphisms and Psychotic Disorders in Populations From North Spain

There is strong biological evidence relating alterations in the serotonergic system with mental disorders. These alterations may be originated at the DNA level by sequence mutations that alter the functioning of serotonin receptors and transporter. To test this hypothesis we investigated three genetic variants of the 5-HT2A receptor (-1438G/A, 102T/C and His452Tyr) and two variants of the serotonin transporter (a VNTR in the second intron and a 44 bp insertion/delition in the promoter region of the gene) in a clinical sample recruited in a human isolate and in surrounding areas in Northern Spain (N = 257) and in ethnically matched controls (N = 334). No clear association was found between 5-HT2A variants and psychosis. However, marginal associations were observed between the 5-HTT LPR and VNTR variants and psychosis (P < or = 0.05) indicating a minor contribution to psychosis of genetic alterations in this gene

De novo erythroleukemia chromosome features include multiple rearrangements, with special involvement of chromosomes 11 and 19

Erythroid leukemia (ERL or AML-M6) is an uncommon subtype of acute myeloid leukemia, the clinical, morphological, and genetic behavior of which needs further characterization. We analyzed a homogeneous group of 23 de novo AML-M6 patients whose bone marrow cells showed complex karyotypes. We also analyzed eight leukemia cell lines with erythroid phenotype, performing detailed molecular cytogenetic analyses, including spectral karyotyping (SKY) in all samples. The main features are: (1) A majority of patients (56%) had hypodiploidy. Loss of genetic material was the most common genetic change, especially monosomies of chromosome 7 or 18, and deletions of chromosome arm 5q. Taken together, 87% of the cases displayed aberrations involving chromosome 5 or 8. (2) We describe a novel, cryptic, and recurrent translocation, t(11;19)(p11.2;q13.1). Another translocation, t(12;21)(p11.2;q11.2), was found to be recurrent in a patient with ERL and in the K562 cell line. (3) MLL gene rearrangements were detected in 20% of cases (three translocations and three amplifications) and, overall, we defined 52 rearrangements (excluding deletions) with a mean of 2.3 translocations per patient. (4) Of the structural aberrations, 21% involved chromosomes 11 and 19. Most of the rearrangements were unbalanced; only 13 reciprocal translocations were observed. The general picture of chromosomal aberrations in cell lines did not reflect what occurred in patient samples. However, both primary samples and cell lines shared three common breakpoints at 19q13.1, 20q11.2, and 21q11.2. This is the first molecular cytogenetic description of the karyotype abnormalities present in patients with ERL. It should assist in the identification of genes involved in erythroleukemogenesis

As múltiplas funções da agricultura familiar: um estudo no assentamento Monte Alegre, região de Araraquara (SP).

A partir da emergência da ideia de sustentabilidade, a agricultura adquiriu novas conotações, associadas não apenas ao aspecto produtivo, mas também à conservação dos recursos naturais e dos territórios rurais, em um reconhecimento de sua multifuncionalidade. Com base nesta noção, que valoriza as funções socioambientais desempenhadas pelas famílias rurais e pelas agriculturas praticadas, o presente artigo analisa um assentamento rural no estado de São Paulo, buscando identificar quais são e de que forma se expressam as funções para além da produção neste território particular. Por meio de uma metodologia de cunho quali-quantitativo, observou-se que, no assentamento em foco, a agricultura encerra em si questões de coesão territorial, manutenção da segurança alimentar, conservação da agrobiodiversidade e de fomento a outras atividades produtivas, sendo o elemento central da reconstrução de um modo de vida rural neste ambiente

Impacto de la intervención con una adaptación grupal del método de musicoterapia BMGIM en pacientes con Enfermedad Inflamatoria Intestinal (Enfermedad de Crohn y COLITIS Ulcerosa)

Las terapias complementarias no farmacológicas han demostrado las mejoras que producen en pacientes crónicos, en especial las terapias psicológicas (Gracie et al., 2017), dentro de las cuales se encuentra la Musicoterapia (MT). Uno de los métodos de Musicoterapia reconocidos a nivel mundial es el método Bonny de Imaginación Guiada con Música (BMGIM), cuya aplicación ha mostrado la mejora al tratar pacientes con ciertas enfermedades crónicas, como artritis reumatoide (Jacobi & Eisenberg, 2001) y fibromialgia (Torres, 2015a, 2015b). Aun así, no hay estudios específicos que evalúen el impacto de un tratamiento basado en una adaptación grupal del BMGIM en pacientes con enfermedad inflamatoria intestinal (EII), concretamente Colitis Ulcerosa (CU y Enfermedad de Crohn (EC), y ese ha sido el objeto de este estudio de tesis doctoral. El objetivo consiste en determinar la eficacia de la intervención con una adaptación grupal del método de MT BMGIM, en la mejora del estado de salud de pacientes con EII (CU y EC).Medicin