Estudio de la resistencia a los antifúngicos en hongos patógenos humanos

Las mejoras en el diagnóstico, el tratamiento y el cuidado de pacientes inmunodeprimidos han incrementado su tasa de supervivencia, pero también han dado lugar al aumento progresivo de otras enfermedades, como las infecciones fúngicas invasoras. A pesar del avance que las herramientas para el diagnóstico de estas infecciones han experimentado, este sigue realizándose de forma tardía en muchas ocasiones, lo que con frecuencia conlleva el inicio de una terapia antifúngica empírica y profiláctica. Este uso generalizado de los antifúngicos es considerado una de las principales causas de la emergencia de la resistencia a estos compuestos entre un gran número de patógenos fúngicos. En los últimos años se ha observado un aumento en el número de cepas que han desarrollado resistencia secundaria entre las especies más prevalentes de los géneros Candida y Aspergillus, así como se han identificado especies que presentan una sensibilidad reducida intrínseca a los antifúngicos, como las especies crípticas de Aspergillus o aquellas pertenecientes a los géneros Fusarium, Scedosporium, Lomentospora o alorden Mucorales..

Currency and commodity return relationship under extreme geopolitical risks: Evidence from the invasion of Ukraine

We examine the relationship between currency and commodity returns around the invasion of Ukraine in February 2022. We find that the expected positive contemporaneous relationship between currency and commodity returns reverses and becomes negative during this period of extreme geopolitical risks. In addition to commodity returns, currency returns around the invasion of Ukraine are significantly affected by geopolitical factors, particularly geographic distance to the war. Our results indicate that a war between two major commodity-exporting countries significantly affects global currency pricing

Bases genéticas de la esquizofrenia: aspectos emocionales, cognitivos y neuroanatómicos.

La esquizofrenia es un desorden mental severo, con una incidencia del 1% y una elevada heredabilidad (alrededor del 80%). Por ello, hay un enorme interés en conocer los factores genéticos implicados en la vulnerabilidad a padecer esquizofrenia. Sin embargo, esta enfermedad presenta una herencia poligénica y además un importante número de factores ambientales parecen influir en su aparición. Asimismo, la heterogeneidad clínica también es elevada y esto dificulta el tener un fenotipo bien definido para el estudio genético. Por ello, el estudio de fenotipos más recortados y mejor definidos puede ser de gran utilidad. En el presente trabajo, se han seleccionado nueve genes de interés. Nuestra hipótesis principal es que variaciones en estos genes modulan la vulnerabilidad a padecer esquizofrenia o alguno de sus rasgos característicos, particularmente las alucinaciones auditivas, el deterioro cognitivo y la disfunción emocional. Como objetivo, nos planteamos el estudio de polimorfismos genéticos en varias muestras caso-control y familiares de España, Alemania y Estados Unidos. Se realizaron análisis de asociación caso-control, basados en familias y estudios de asociación con diferentes escalas clínicas. Asimismo, se estudió el impacto de ciertos polimorfismos sobre fenotipos de neuroimagen estructural y funcional. Los resultados más interesantes fueron los siguientes: por una parte, diferentes genes del sistema serotoninérgico (principalmente los genes SLC6A4 y HTR2A) parecían influir en el estado emocional del paciente, así como en la respuesta emocional del paciente a las alucinaciones auditivas. Además, el gen ASPM se asoció con el riesgo de psicosis y con diferentes parámetros cognitivos y de neuroimagen. Otros genes como NOS1, STMN1, PDE4D y PLEKHB1 parecían influir sobre el riesgo de psicosis, así como sobre las puntuaciones obtenidas en diferentes escalas psicopatológicas, si bien en estos casos la significación fue menor. Todos estos resultados permiten proponer un modelo de vulnerabilidad, según el cual ciertos genes tendrían un mayor efecto sobre la vulnerabilidad a sufrir esquizofrenia, mientras que otros genes influirían sobre la severidad de ciertos síntomas. Además, nuestros resultados apoyan la existencia de una vulnerabilidad genética a respuestas emocionales aberrantes, que podría estar modulada por la variación en ciertos genes, tales como el transportador de serotonina.Schizophrenia is a severe psychotic mental disorder, with a prevalence of around 1% in general population. It is well known that this disease presents a high heritability (around 80%). For this reason, there is a great interest in discovering the genetic factors affecting the risk for schizophrenia. However, due to the polygenic inheritance of this disorder, it is particularly hard to discover schizophrenia-related genes. Moreover, it has been hypothesized that an important number of environmental factors of different nature may affect the vulnerability to schizophrenia. Furthermore, schizophrenia is a clinically heterogeneous disorder and it can be particularly difficult to have a well-defined phenotype for genetic studies. For all these reasons, we consider that it is important to study the neurobiology of schizophrenia as a global entity, but also to complement these studies with other approaches, for example through the use of other alternative phenotypes, such as cognitive impairment, electrophysiological responses or auditory hallucinations, for example. In the present study, different candidate genes were selected. Our main hypothesis is that variations in these nine genes modulate the vulnerability to schizophrenia and some of their most characteristic and important features, particularly auditory hallucinations, cognitive impairment and, finally, the emotional dysfunction associated to schizophrenia. To test this hypothesis, we focused the study on the analysis of genetic polymorphisms (mainly single nucleotide polymorphisms) in three case-control samples from Spain, Germany and United States and a family sample from the United States. All samples were of Caucasian origin. Different analysis were performed, namely case-control association analysis, family-based association analysis (in some cases) and association analysis with clinical measures that corresponded to different psychopathological scales (BPRS, KGV, PANSS and PSYRATS for auditory hallucinations and delusions). Moreover, we also assessed the impact of certain genetic polymorphisms on functional and structural neuroimaging phenotypes, which evaluated both cognitive and emotional aspects. The most interesting results were the following: first, several polymorphisms from serotonergic system genes (mainly SLC6A4 and HTR2A genes, but also TPH2 gene to a lesser extent) appeared to modulate the patient's emotional state, including the emotional response to auditory hallucinations, assessed with clinical scales and neuroimaging techniques. Moreover, the positive selection gene ASPM, involved in neurodevelopmental processes, was associated with the risk for psychosis and with different cognitive and neuroimaging measures in both the Spanish and the American sample. Other genes such as NOS1, STMN1, PDE4D and PLEKHB1 also appeared to influence the risk for psychosis and the scores in some psychopathological scales, although in these cases significance was weaker.All these findings allow us to propose a vulnerability model. According to this model, some genes would have a major effect on the vulnerability to schizophrenia, while other genes would have an effect on the severity to certain symptoms. Regarding the vulnerability to auditory hallucinations, our results also support the existence of a genetic vulnerability to aberrant emotional responses, which could be modulated by the variation in different genes, such as the serotonin transporter gene, among others

The experiences of staff at children’s hospices who use ‘cold’ facilities to care for families after the death of an infant: A qualitative study

Background: Children’s hospices in the UK have developed to incorporate various ‘cold’ facilities, which allow families to spend time with their baby after they have died. To date, no research has explored the impact on staff of providing this form of care alongside their usual roles within the hospice. This thesis aims to understand the experiences of stress in those providing palliative care through a systematic review, and explore the experiences of staff who are supporting families using ‘cold’ facilities within a paediatric hospice after the death of their infant. Methods: A mixed-method systematic review and narrative synthesis of the literature was conducted using electronic databases and relevant reference sections of papers to evaluate the experience of stress in staff members who provide care in palliative services. Alongside this, a qualitative study was conducted using semi-structured interviews with seven members of staff at regional children’s hospices to explore their experiences and the sense they made of their work. Data were transcribed and analysed using thematic analysis. Results: The systematic review found 12 studies which met the inclusion criteria. Quality was appraised and data was analysed using narrative synthesis. Results reported the levels of stress, types of stressor and coping strategies identified. The thematic analysis of the qualitative study identified two key themes (‘Challenges within the pathway’ and ‘Ways that challenges are met’) and 12 subthemes. Conclusions: The research highlighted the unique experiences of staff in providing care using ‘cold’ facilities. Some challenges are specific to this care pathway, though others appear in line with those faced in overall paediatric palliative care. Challenges are ameliorated through both cognitive and behavioural coping mechanisms and the 3 importance of an open and supportive workplace culture is emphasised in ensuring staff well-being. Limitations and directions for future research are considered

Point Mutations in the 14-α Sterol Demethylase Cyp51A or Cyp51C Could Contribute to Azole Resistance in Aspergillus flavus.

Infections caused by Aspergillus species are being increasingly reported. Aspergillus flavus is the second most common species within this genus causing invasive infections in humans, and isolates showing azole resistance have been recently described. A. flavus has three cyp51-related genes (cyp51A, cyp51B, and cyp51C) encoding 14-α sterol demethylase-like enzymes which are the target of azole drugs. In order to study triazole drug resistance in A. flavus, three strains showing reduced azole susceptibility and 17 azole susceptible isolates were compared. The three cyp51-related genes were amplified and sequenced. A comparison of the deduced Cyp51A, Cyp51B, and Cyp51C protein sequences with other protein sequences from orthologous genes in different filamentous fungi led to a protein identity that ranged from 50% to 80%. Cyp51A and Cyp51C presented several synonymous and non-synonymous point mutations among both susceptible and non-susceptible strains. However, two amino acid mutations were present only in two resistant isolates: one strain harbored a P214L substitution in Cyp51A, and another a H349R in Cyp51C that also showed an increase of cyp51A and cyp51C gene expression compared to the susceptible strain ATCC2004304. Isolates that showed reduced in vitro susceptibility to clinical azoles exhibited a different susceptibility profile to demethylation inhibitors (DMIs). Although P214L substitution might contribute to azole resistance, the role of H349R substitution together with changes in gene expression remains unclear.This research was funded by Fondo de Investigacion Sanitaria (FIS PI18CIII/00045) and also by Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/CIII/0004/0003), co-financed by European Development Regional Fund ERDF “A way to achieve Europe”, Operative program Intelligent Growth 2014-2020. J.L. holds a predoctoral fellowship from the Fondo de Investigación Sanitaria (F17CIII/00037).S

Impact of the AHI1 Gene on the Vulnerability to Schizophrenia: A Case-Control Association Study

Background: The Abelson helper integration-1 (AHI1) gene is required for both cerebellar and cortical development in humans. While the accelerated evolution of AHI1 in the human lineage indicates a role in cognitive (dys)function, a linkage scan in large pedigrees identified AHI1 as a positional candidate for schizophrenia. To further investigate the contribution of AHI1 to the susceptibility of schizophrenia, we evaluated the effect of AHI1 variation on the vulnerability to psychosis in two samples from Spain and Germany. Methodology/Principal Findings: 29 single-nucleotide polymorphisms (SNPs) located in a genomic region including the AHI1 gene were genotyped in two samples from Spain (280 patients with psychotic disorders; 348 controls) and Germany (247 patients with schizophrenic disorders; 360 controls). Allelic, genotypic and haplotype frequencies were compared between cases and controls in both samples separately, as well as in the combined sample. The effect of genotype on several psychopathological measures (BPRS, KGV, PANSS) assessed in a Spanish subsample was also evaluated. We found several significant associations in the Spanish sample. Particularly, rs7750586 and rs911507, both located upstream of the AHI1 coding region, were found to be associated with schizophrenia in the analysis of genotypic (p = 0.0033, and 0.031,respectively) and allelic frequencies (p = 0.001 in both cases). Moreover, several other risk and protective haplotypes were detected (0.006,p,0.036). Joint analysis also supported the association of rs7750586 and rs911507 with the risk for schizophrenia. The analysis of clinical measures also revealed an effect on symptom severity (minimum P value = 0.0037). Conclusions/Significance: Our data support, in agreement with previous reports, an effect of AHI1 variation on the susceptibility to schizophrenia in central and southern European populations

Hollow Fiber Membranes of PCL and PCL/Graphene as Scaffolds with Potential to Develop In Vitro Blood—Brain Barrier Models

There is a huge interest in developing novel hollow fiber (HF) membranes able to modulate neural differentiation to produce in vitro blood–brain barrier (BBB) models for biomedical and pharmaceutical research, due to the low cell-inductive properties of the polymer HFs used in current BBB models. In this work, poly(ε-caprolactone) (PCL) and composite PCL/graphene (PCL/G) HF membranes were prepared by phase inversion and were characterized in terms of mechanical, electrical, morphological, chemical, and mass transport properties. The presence of graphene in PCL/G membranes enlarged the pore size and the water flux and presented significantly higher electrical conductivity than PCL HFs. A biocompatibility assay showed that PCL/G HFs significantly increased C6 cells adhesion and differentiation towards astrocytes, which may be attributed to their higher electrical conductivity in comparison to PCL HFs. On the other hand, PCL/G membranes produced a cytotoxic effect on the endothelial cell line HUVEC presumably related with a higher production of intracellular reactive oxygen species induced by the nanomaterial in this particular cell line. These results prove the potential of PCL HF membranes to grow endothelial cells and PCL/G HF membranes to differentiate astrocytes, the two characteristic cell types that could develop in vitro BBB models in future 3D co-culture systems.This research was funded by IDIVAL (INNVAL 17/20), MINECO/EIG-Concert Japan (X-MEM PCI2018-092929 project, International Joint Program 2018) and MINECO/Spain Feder (CTM-2016-75509-R project)

Leptin-resistant Zucker rats with trinitrobenzene sulfonic acid colitis present a reduced inflammatory response but enhanced epithelial damage

The study was funded the following grants of the Ministerio de Economía y Competitividad and the Fondo Europeo de Desarrollo Regional FEDER (SAF2011-22922, SAF2011-22812, BFU2014- 57736-P, and AGL2014-58883-R) and Junta de Andalucía (CTS164, CTS235, and CTS6736). B. Rivero-Guti errez, R. Gámez-Belmonte, and M. Arredondo-Amador were supported by fellowships from the Ministerio de Educación.The role of leptin in the development of intestinal inflammation remains controversial, since proinflammatory and anti-inflammatory effects have been described. This study describes the effect of the absence of leptin signaling in intestinal inflammation. Experimental colitis was induced by intrarectal administration of trinitrobenzene sulfonic acid (TNBS) to lean and obese Zucker rats (n = 10). Effects on inflammation and mucosal barrier were studied. Bacterial translocation and LPS concentration were evaluated together with colonic permeability to 4-kDa FITC-dextran. Obese Zucker rats showed a lower intestinal myeloperoxidase and alkaline phosphatase activity, reduced alkaline phosphatase sensitivity to levamisole, and diminished colonic expression of Nos2, Tnf, and Il6, indicating attenuated intestinal inflammation, associated with attenuated STAT3, AKT, and ERK signaling in the colonic tissue. S100a8 and Cxcl1 mRNA levels were maintained, suggesting that in the absence of leptin signaling neutrophil activation rather than infiltration is hampered. Despite the lower inflammatory response, leptin resistance enhanced intestinal permeability, reflecting an increased epithelial damage. This was shown by augmented LPS presence in the portal vein of colitic obese Zucker rats, associated with induction of tissue nonspecific alkaline phosphatase, LPS-binding protein, and CD14 hepatic expression (involved in LPS handling). This was linked to decreased ZO-1 immunoreactivity in tight junctions and lower occludin expression. Our results indicate that obese Zucker rats present an attenuated inflammatory response to TNBS, but increased intestinal epithelial damage allowing the passage of bacterial antigens.Ministerio de Economía y Competitividad and the Fondo Europeo de Desarrollo Regional FEDER (SAF2011-22922, SAF2011-22812, BFU2014- 57736-P, and AGL2014-58883-R)Junta de Andalucía (CTS164, CTS235, and CTS6736)Ministerio de Educació

Phytochemical Characterization and Fixed Carbon by Ignition of Two Varieties of Cocoa Husk (Theobroma Cacao L.) for Sustainable Use of the Residue

One reality for Colombia is that the government has considered cocoa production to be of great economic importance and plans to progressively increase the areas under cultivation. In this context, only the seed, which represents approximately 10 % of the weight of the fruit, is used for cocoa production. The waste generated consists of the husk or pod, which is a focus for the propagation of pathogens of the Phytophora spp. genus, the main cause of economic losses in cocoa farming. Therefore, this project evaluated the potential use of cocoa pods of ICS-95 and CCN-51 clone based on bromatological, phytochemical, volatile material, and fixed carbon analyses of harvest residues. Laboratory tests were carried out at the Fundación Universitaria Agraria de Colombia - UNIAGRARIA, in the Nutrition and Animal Feeding laboratories, as well as in the Phytochemistry laboratory. The bromatological analysis and preliminary phytochemistry were carried out under the Colombian technical standard, while moisture was determined with the use of standard D3173-87, volatile matter with standard D3175-89 (02), ash with standard D3172-89 (02) and fixed carbon ignition with standard 3172- 89 (02); The latter, considered as the part that is not volatile and burns in solid state of the lignocellulosic material, establishing the difference between the sum of residual moisture, moisture, ash and volatile material and 100. The analysis of the data was carried out in the IBM SPSS Statistics package using a simple analysis of variance and a multiple range test for comparison of means. The comparative analysis of the variables shows a statistically significant difference in fixed carbon content according to the variety under study, but greater than 20% in both cases. The above results agree with those indicated for the % moisture, the response variables of the bromatological analysis, the phytochemical results, and the content of volatile compounds. Keywords: Agricultural, plant fisiology, by-products, agribusiness