G6PD overexpression protects from oxidative stress and age-related hearing loss

Aging of the auditory system is associated with the incremental production of reactive oxygen species (ROS) and the accumulation of oxidative damage in macromolecules, which contributes to cellular malfunction, compromises cell viability, and, ultimately, leads to functional decline. Cellular detoxification relies in part on the production of NADPH, which is an important cofactor for major cellular antioxidant systems. NADPH is produced principally by the housekeeping enzyme glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the rate-limiting step in the pentose phosphate pathway. We show here that G6PD transgenic mice (G6PD-Tg), which show enhanced constitutive G6PD activity and NADPH production along life, have lower auditory thresholds than wild-type mice during aging, together with preserved inner hair cell (IHC) and outer hair cell (OHC), OHC innervation, and a conserved number of synapses per IHC. Gene expression of antioxidant enzymes was higher in 3-month-old G6PD-Tg mice than in wild-type counterparts, whereas the levels of pro-apoptotic proteins were lower. Consequently, nitration of proteins, mitochondrial damage, and TUNEL apoptotic cells were all lower in 9-month-old G6PD-Tg than in wild-type counterparts. Unexpectedly, G6PD overexpression triggered low-grade inflammation that was effectively resolved in young mice, as shown by the absence of cochlear cellular damage and macrophage infiltration. Our results lead us to propose that NADPH overproduction from an early stage is an efficient mechanism to maintain the balance between the production of ROS and cellular detoxification power along aging and thus prevents hearing loss progression.Secretaría de Estado de Investigación, Desarrollo e Innovación, Grant/Award Number: MINECO/FEDER SAF2017-86107-R; Comunidad de Madrid, Grant/Award Number: FEDER/CM-B2017/BMD-368

La legitimidad en el derecho colombiano

Dentro de la estructura social colombiana, existen formas de vida tan diversas como regiones y dialectos hay a lo largo y ancho de la geografía nacional. De tal forma, no existe un concepto unívoco de bien común que determine la legitimidad del ordenamiento jurídico nacional, como consecuencia de las características sociológicas de nuestra nación. No hay un consenso en el ethos colombiano, se impone uno sobre los otros. El Presidente de la República encarna el ethos dominante y a su vez tiene una injerencia determinante tanto en la conformación de las altas Cortes como en el poder legislativo, por lo tanto, cuando la Corte Constitucional interpreta la Constitución y cuando el Congreso legisla, lo hacen de acuerdo con el ethos imperanteAbstract: In Colombian social structure there are life forms as diverse as there are dialects and regions across the length and breadth of the country. Thus, there is no uniform concept of the common good that determines the legi- timacy of the national legal system as a result of the sociological characteristics of our nation. There isn’t a consensus in the Colombian ethos; one will be imposed over the others. The president of the republic embodies the dominant ethos and has a determining interference in the conformation of the High Courts as well as in the legislative power, and therefore when the Constitutional Court interprets the constitution and the Parliament enacts laws, they do it according to the prevailing ethos

The economic ethos as a legitimate factor in Colombian legal system

El presente documento de reflexión realiza un análisis del planteamiento consistente en afirmar que la legitimidad del ordenamiento jurídico en Colombia radica en el ethos económico. Efectivamente si se considera que la legitimidad del ordenamiento jurídico colombiano no es fruto del consenso, entonces surge la pregunta, ¿radica en la voluntad del ethos económico dominante? A esta pregunta se pretende responder en este artículo. La estructura social colombiana tiene formas de vida tan diversas como regiones y culturas hay a lo largo y ancho de la geografía nacional, lo cual conlleva que no exista un concepto unívoco de bien común que determine la legitimidad del ordenamiento jurídico nacional. Se observa entonces que el factor económico es el que legitima el derecho colombiano en la medida que la producción normativa responde a los intereses de los grupos que manejan el ethos económico, lo cual evidencia que la legitimidad de nuestro derecho no radica en el conjunto de costumbres, valores, tradiciones, símbolos y hábitos que definen la identidad de nuestros nacionales, sino en el factor económico y en los intereses de los grupos sociales que lo detentan.Abstract: This discussion paper analyzes a consistent approach in asserting that the legitimacy of law in Colombia is in the economic ethos. Indeed assuming that the legitimacy of the Colombian legal system is not the result of consensus, and then the question lies in the will of the dominant economic ethos? This question seeks to answer in this article. The Colombian social structure is composed by as many different lifestyles as many are the regions and cultures on the national territory. This complexity results in the fact that it does not exist a univocal concept of common good that is able to determine the legitimacy of the national juridical order. It is anyhow clear that the element with the strongest influence is the economical one, as far as the production of laws corresponds to the interests of the economical leading group. Therefore the legitimacy of our juridical order is not based on the customs, values, traditions and habits that are the identity of our nation, but on the economical factor and on the interests of the leading social groups

La legitimidad en el derecho colombiano

Dentro de la estructura social colombiana existen formas de vida tan diversas como regiones y dialectos hay a lo largo y ancho de nuestra geografía. Por ello, no existe un concepto unívoco de bien común que determine la legitimidad del ordenamiento jurídico nacional, debido a las características sociológicas de nuestra nación. No hay un consenso en el ethos colombiano, se impone uno sobre los otros. El Presidente de la República encarna el ethos dominante, y a su vez tiene una injerencia determinante tanto en la conformación de las altas Cortes como en el poder legislativo. Por esto, cuando la Corte Constitucional interpreta la Constitución y cuando el Congreso legisla, lo hacen de acuerdo con el ethos imperante

Dual-Specificity Phosphatase 1 (DUSP1) Has a Central Role in Redox Homeostasis and Inflammation in the Mouse Cochlea.

Stress-activated protein kinases (SAPK) are associated with sensorineural hearing loss (SNHL) of multiple etiologies. Their activity is tightly regulated by dual-specificity phosphatase 1 (DUSP1), whose loss of function leads to sustained SAPK activation. Dusp1 gene knockout in mice accelerates SNHL progression and triggers inflammation, redox imbalance and hair cell (HC) death. To better understand the link between inflammation and redox imbalance, we analyzed the cochlear transcriptome in Dusp1-/- mice. RNA sequencing analysis (GSE176114) indicated that Dusp1-/- cochleae can be defined by a distinct profile of key cellular expression programs, including genes of the inflammatory response and glutathione (GSH) metabolism. To dissociate the two components, we treated Dusp1-/- mice with N-acetylcysteine, and hearing was followed-up longitudinally by auditory brainstem response recordings. A combination of immunofluorescence, Western blotting, enzymatic activity, GSH levels measurements and RT-qPCR techniques were used. N-acetylcysteine treatment delayed the onset of SNHL and mitigated cochlear damage, with fewer TUNEL+ HC and lower numbers of spiral ganglion neurons with p-H2AX foci. N-acetylcysteine not only improved the redox balance in Dusp1-/- mice but also inhibited cytokine production and reduced macrophage recruitment. Our data point to a critical role for DUSP1 in controlling the cross-talk between oxidative stress and inflammation

Resposta emocional de pacientes cardiológicos críticos durante a higiene em cuidados intensivos: um estudo prospectivo e descritivo

Objetivo: analizar la respuesta emocional de pacientes conscientes en estado crítico durante la higiene diaria en una unidad de cuidados intensivos cardiológicos y compararla en función de experiencias previas o no. Método: estudio prospectivo y descriptivo. Encuesta ad hoc de 30 ítems realizada a 148 pacientes y basada en la higiene del primer día. Se formulan preguntas sobre los sentimientos durante la higiene y aspectos positivos y negativos de la experiencia. Se compara a los pacientes en función de si se los había higienizado con anterioridad. Resultados: el 67,6% fueron hombres y la media de edad fue de 67±15 años. El 45,9% presentó conformismo, el 27% sintió vergüenza y el 86,3% agradeció que le hablaran durante la higiene. Al 33,1% de los pacientes nunca les habían realizado higiene en la cama, eran significativamente más jóvenes y solteros, y tenían menor sensación de limpieza. El 32% expresó que le gustaría que un familiar colaborase en la higiene. Conclusión: los pacientes no sienten que se invade su intimidad cuando se los higieniza y aprecian la comunicación con el personal sanitario durante estos cuidados. Los pacientes a quienes no les habían realizado higiene en la cama previamente son más jóvenes, sienten mayor vergüenza y les molestan más las interrupciones, siendo más conscientes de ellas.Objetivo: analisar a resposta emocional de pacientes críticos conscientes durante a higiene diária em uma unidade de terapia intensiva cardíaca e compará-la considerando ou não as experiências prévias. Método: estudo prospectivo e descritivo. Foi aplicado questionário ad hoc de 30 itens a 148 pacientes, com base na higiene do primeiro dia. Foram feitas perguntas sobre sentimentos durante a higiene e aspectos positivos e negativos da experiência. Os pacientes foram comparados considerando o fato de terem sido higienizados anteriormente. Resultados: 67,6% eram homens e a idade média foi de 67±15 anos. 45,9% apresentavam conformismo, 27% se sentiram envergonhados e 86,3% estavam gratos por terem conversado com eles durante a higiene; 33,1% dos pacientes acamados nunca haviam recebido cuidados de higiene no leito, eram significativamente mais jovens e solteiros, e tinham um senso de limpeza mais baixo; 32% expressaram que gostariam que um membro da família ajudasse na higiene. Conclusão: os pacientes não se sentiram invadidos em sua intimidade quando receberam os cuidados de higiene e apreciaram a comunicação com o pessoal de saúde durante o procedimento. Os pacientes que não tinham recebido cuidados de higiene no leito anteriormente são mais jovens, sentem-se mais constrangidos e mais incomodados pelas interrupções, sendo mais conscientes delas.Objective: to analyze the emotional response of critically-ill conscious patients during daily hygiene procedures in a Cardiology Intensive Care Unit and to compare it based on the existence of previous experiences or not. Method: a prospective and descriptive study. A 30-item ad hoc survey based on the first-day hygiene procedures was applied to 148 patients. Questions are asked about the feelings during the hygiene procedures and about positive and negative aspects of the experience. The patients are compared based on whether they had been already subjected to hygiene procedures or not. Results: 67.6% were men and their mean age was 67±15 years old; 45.9% proved to be satisfied, 27% felt embarrassment and 86.3% were grateful to the professionals for talking to them during the hygiene procedures. 33.1% of the patients had never been subjected to hygiene procedures in bed, were significantly younger and single, and presented a lower cleanliness sensation. 32% stated that they would like for a family member to collaborate in the hygiene procedures. Conclusion: the patients do not feel that their intimacy is invaded when they are subjected to hygiene procedures and appreciate communication with the health personnel while this care is provided. Those who had never been subjected to hygiene procedures in bed are younger, feel more embarrassed and are more disturbed by interruptions, in addition to being more aware of them

Non-Immersive Virtual Reality to Improve Balance and Reduce Risk of Falls in People Diagnosed with Parkinson’s Disease: A Systematic Review

(1) Objective: To evaluate the effectiveness of non-immersive virtual reality in reducing falls and improving balance in patients diagnosed with Parkinson’s disease. (2) Methods: The following databases were searched: PUBMED, PEDro, Scielo, CINAHL, Web of Science, Dialnet, Scopus and MEDLINE. These databases were searched for randomized controlled trials published using relevant keywords in various combinations. The methodological quality of the articles was evaluated using the PEDro scale. (3) Results: A total of 10 studies with a total of 537 subjects, 58.7% of which (n = 315) were men, have been included in the review. The age of the participants in these studies ranged between 55 and 80 years. Each session lasted between 30 and 75 min, and the interventions lasted between 5 and 12 weeks. These studies showed that non-immersive virtual reality is effective in reducing the number of falls and improving both static and dynamic balance in patients diagnosed with Parkinson’s disease. Results after non-immersive virtual reality intervention showed an improvement in balance and a decrease in the number and the risk of falls. However, no significant differences were found between the intervention groups and the control groups for all the included studies regarding balance. (4) Conclusions: There is evidence that non-immersive virtual reality can improve balance and reduce the risk and number of falls, being therefore beneficial for people diagnosed with Parkinson’s disease

Tumor cell and immune cell profiles in primary human glioblastoma: Impact on patient outcome

© 2020 The Authors.The distribution and role of tumor-infiltrating leucocytes in glioblastoma (GBM) remain largely unknown. Here, we investigated the cellular composition of 55 primary (adult) GBM samples by flow cytometry and correlated the tumor immune profile with patient features at diagnosis and outcome. GBM single-cell suspensions were stained at diagnosis (n = 44) and recurrence following radiotherapy and chemotherapy (n = 11) with a panel of 8-color monoclonal antibody combinations for the identification and enumeration of (GFAPCD45) tumor and normal astrocytic cells, infiltrating myeloid cells —i.e. microglial and blood-derived tumor-associated macrophages (TAM), M1-like, and M2-like TAM, neutrophils. and myeloid-derived suppressor cells (MDSC)— and tumor-infiltrating lymphocytes (TIL) —i.e. CD3T-cells and their TCD4, TCD8, TCD4CD8, and (CD25CD127) regulatory (T-regs) subsets, (CD19CD20) B-cells, and (CD16) NK-cells—. Overall, GBM samples consisted of a major population (mean ± 1SD) of tumor and normal astrocytic cells (73% ± 16%) together with a significant but variable fraction of immune cells (24% ± 18%). Within myeloid cells, TAM predominated (13% ± 12%) including both microglial cells (10% ± 11%) and blood-derived macrophages (3% ± 5%), in addition to a smaller proportion of neutrophils (5% ± 9%) and MDSC (4% ± 8%). Lymphocytes were less represented and mostly included TCD4 (0.5% ± 0.7%) and TCD8 cells (0.6% ± 0.7%), together with lower numbers of TCD4CD8 T-cells (0.2% ± 0.4%), T-regs (0.1% ± 0.2%), B-lymphocytes (0.1% ± 0.2%) and NK-cells (0.05% ± 0.05%). Overall, three distinct immune profiles were identified: cases with a minor fraction of leucocytes, tumors with a predominance of TAM and neutrophils, and cases with mixed infiltration by TAM, neutrophils, and T-lymphocytes. Untreated GBM patients with mixed myeloid and lymphoid immune infiltrates showed a significantly shorter patient overall survival versus the other two groups, in the absence of gains of the EGFR gene (p = 0.02). Here we show that immune cell infiltrates are systematically present in GBM, with highly variable levels and immune profiles. Patients with mixed myeloid and T-lymphoid infiltrates showed a worse outcome.Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and fondos FEDER, Grant/Award Number: CB16/12/00400 and ISCIII PI16/0476; Consejería de Sanidad Junta de Castilla y León, Gerencia Regional de Salud, Spain, Grant/Award Number: GRS2049/A/1

Young Nursing Student’s Knowledge and Attitudes about Contraceptive Methods

We would like to thank all the nursing students who voluntarily participated in this studyPurpose: Adolescence is considered a period in which individuals are particularly at risk of negative consequences related to sexual health. Increased knowledge levels have traditionally been used as an indicator of the effectiveness of educational programs, but attitudes are not addressed and are a key element for the success of such programs. The aim of this study is to determine the level of knowledge and attitudes toward the use of contraceptive methods among nursing students. A multicenter cross-sectional study was carried out. In total, 2914 university students (aged 18–25 years) enrolled in the study. Participants completed two validated scales to measure knowledge level and attitudes toward contraceptive use. Nursing degree students who received training about contraceptives obtained a success rate of over 70%, compared to 15.3% among students who had not received such training (p < 0.001). The mean attitude score was 43.45 points (10–50), but there were no significant differences in terms of student training (p = 0.435), although they were significantly higher among students who used contraceptives at first or last sexual intercourse (p < 0.001). There was a significant weak correlation between the level of knowledge and attitudes toward the use of contraceptives. An adequate level of knowledge about sexuality and contraceptive methods does not correspond to positive attitudes toward their use, although having an excellent attitude toward contraceptive use is related to their use during youth and adolescence

Young Nursing Student’s Knowledge and Attitudes about Contraceptive Methods

Purpose: Adolescence is considered a period in which individuals are particularly at risk of negative consequences related to sexual health. Increased knowledge levels have traditionally been used as an indicator of the effectiveness of educational programs, but attitudes are not addressed and are a key element for the success of such programs. The aim of this study is to determine the level of knowledge and attitudes toward the use of contraceptive methods among nursing students. A multicenter cross-sectional study was carried out. In total, 2914 university students (aged 18–25 years) enrolled in the study. Participants completed two validated scales to measure knowledge level and attitudes toward contraceptive use. Nursing degree students who received training about contraceptives obtained a success rate of over 70%, compared to 15.3% among students who had not received such training (p < 0.001). The mean attitude score was 43.45 points (10–50), but there were no significant differences in terms of student training (p = 0.435), although they were significantly higher among students who used contraceptives at first or last sexual intercourse (p < 0.001). There was a significant weak correlation between the level of knowledge and attitudes toward the use of contraceptives. An adequate level of knowledge about sexuality and contraceptive methods does not correspond to positive attitudes toward their use, although having an excellent attitude toward contraceptive use is related to their use during youth and adolescence