Proteasome-dependent degradation of histone H1 subtypes is mediated by its C-terminal domain.

Histone H1 is involved in chromatin compaction and dynamics. In human cells, the H1 complement is formed by different amounts of somatic H1 subtypes, H1.0-H1.5 and H1X. The amount of each variant depends on the cell type, the cell cycle phase, and the time of development and can be altered in disease. However, the mechanisms regulating H1 protein levels have not been described. We have analyzed the contribution of the proteasome to the degradation of H1 subtypes in human cells using two different inhibitors: MG132 and bortezomib. H1 subtypes accumulate upon treatment with both drugs, indicating that the proteasome is involved in the regulation of H1 protein levels. Proteasome inhibition caused a global increase in cytoplasmatic H1, with slight changes in the composition of H1 bound to chromatin and chromatin accessibility and no alterations in the nucleosome repeat length. The analysis of the proteasome degradation pathway showed that H1 degradation is ubiquitin-independent. The whole protein and its C-terminal domain can be degraded directly by the 20S proteasome in vitro. Partial depletion of PA28γ revealed that this regulatory subunit contributes to H1 degradation within the cell. Our study shows that histone H1 protein levels are under tight regulation to prevent its accumulation in the nucleus. We revealed a new regulatory mechanism for histone H1 degradation, where the C-terminal disordered domain is responsible for its targeting and degradation by the 20S proteasome, a process enhanced by the regulatory subunit PA28γ.

Genital chronic graft-versus-host disease: an unmet need that requires trained gynecologists.

OBJECTIVE: Menopause and chronic graft-versus-host disease (cGvHD) are the leading causes of morbidity after allogeneic hematopoietic stem cell transplantation (alloHSCT). Genitalia are one of the target organs of cGvHD causing sexual dysfunction and local symptoms, which may impair women's quality of life. The aim of this study is to describe the prevalence and clinical characteristics of genital cGvHD. METHODS: A retrospective cross-sectional observational study was performed including 85 women with alloHSCT. All women were diagnosed and counseled by a trained gynecologist. Health-related quality of life was assessed by the Cervantes Short-Form Scale and sexual function was evaluated by the Female Sexual Function Index. RESULTS: Seventeen women (20%) included in the study were diagnosed with genital cGvHD. The main complaints were vulvovaginal dryness (42.2%) and dyspareunia (29.4%), the presence of erythema/erythematous plaques (52.9%) being the most frequent sign. Median time from transplant to diagnosis of genital cGvHD was 17 months among those with mild involvement, 25 months for moderate and 42 months for severe forms. Mortality was 29.4% in patients who developed cGvHD with genital involvement versus 8.8% among those without (p = 0.012). CONCLUSION: Early gynecological evaluation might allow to identify patients with mild forms of genital cGvHD, potentially enabling better management and improved outcomes.

Effects of ascorbic acid addition on the oxidative stress response of Oryza sativa L. plants to As(V) exposure.

Accumulation of noxious elements in the edible part of crops and its impact on food safety is of increasing concern. Rice is one of the major staple food crops worldwide, including arsenic (As)-polluted areas, in which dietary As exposure is becoming a widespread health threat. Plant chemical priming has been shown to be an effective strategy to enhance tolerance to environmental stresses, including metal(loid) exposure. The priming effect of ascorbic acid (AsA) was assessed in rice seedlings exposed to As(V) in a hydroponics experiment. AsA treatment (co-addition to the growing media concomitantly (t0) or 24 h in advance (t24)) prevented an excessive accumulation of As in the roots (that decreased âˆ¼ 60%) and stimulated the activities of photosynthetic and antioxidant attributes (∼1.2-fold) in the aerial part of the plants. The increase in proline levels in both shoots (∼2.1-fold) and roots (∼2.4-fold) was found to be the most sensitive stress parameter, and was able to reflect the AsA-induced reduction of As toxic effects (concentrations back to Control levels, both simultaneously added or added as a pretreatment) in the aerial part of the plants. However, the phytotoxic effects related to As exposure were not fully prevented by priming with AsA, and further research is needed to find alternative priming approaches.

Stress responses in captive Crocodylus moreletii associated with metal exposure.

Environmental pollution by metals has repercussions on wildlife health. It is known that some metals can have an influence on the neuroendocrine stress response, and at the same time, metals have pro-oxidant effects that can overwhelm the antioxidant system and cause oxidative stress. This study evaluates the association of metals with neuroendocrine stress activity and biomarkers of oxidative stress in 42 captive female Morelet's crocodiles (Crocodylus moreletii). We measured five metals of ecotoxicological importance (Hg, Cd, Pb, Cu and Zn), and three biomarkers of the oxidative stress response in the liver: glutathione (GSH) and glutathione disulfide (GSSG) as markers for antioxidant system and thiobarbituric acid reactive substances (TBARS) for oxidative damage. We also measured one biomarker of the neuroendocrine response to stress: corticosterone (B) in blood plasma. The mean ± SD concentrations of metals in the liver expressed in µg/g (dw) were: Cd: 0.004 ± 0.003, Hg: 0.014 ± 0.019, Cu: 0.017 ± 0.013, Zn: 0.043 ± 0.035, Pb: 0.16 ± 0.256. The mean ± SD of GSH was 0.42 ± 0.35 nmol/mg protein, the mean ± SD of GSSG was 0.24 ± 0.20 nmol/mg protein, the mean ± SD concentrations of TBARS were 0.36 ± 0.21 nmol/mg protein, and the mean ± SD of B was 393.57 ± 405.14 pg/mL. Hg presented a significant negative relationship with corticosterone. Cd had a negative relationship with both GSH and GSSG; meanwhile, Zn showed a negative relationship with TBARS levels, could be a protective element against hepatic oxidative damage. Finally, B had negative relationship with oxidative damage. The connection found between Hg and the neuroendocrine stress response, as well as the correlations of Cd and Zn with oxidative damage and antioxidant activity should be studied further, given their toxicological importance and implications for the conservation of C. moreletii and other crocodilians.

Revisión de la medicación tras episodio de hipotensión / Review of medication after hypotension episode

PRESENTACIÓN: mujer de 86 años, polimedicada, tiene dos stents, padece diverticulitis e insuficiencia renal incipiente. Desde hace días está cansada, fatigada y mareada y como se siente peor acude a la farmacia comunitaria a medirse la presión arterial. Siguiendo el protocolo establecido en las guías se obtienen los siguientes valores:1º medida: PAS/PAD 12/6 (mmHg) FC 82 ppm2º medida: PAS/PAD 9.6/4 (mmHg) FC 86 ppm3º medida (tras 15 minutos) PAS/PAD 9/4 (mmHg) FC 85 ppm.EVALUACIÓN: con el fin de valorar si existe algún problema relacionado con los medicamentos (PRM) se revisan las prescripciones de su receta electrónica y se identifican los siguientes: Rifamixina: inseguridad no cuantitativa, pauta 1/8 h continuada durante años. En ficha técnica se indica no sobrepasar los 7 días de tratamiento. Furosemida: inseguridad cuantitativa, pauta en receta 3/24 (1-0.5-0). Desde hace un mes la pauta utilizada es, bajo indicación médica telefónica (1.5-1-0) Metamizol: inseguridad no cuantitativa, pauta 1/8 h. En ficha técnica se indica del riesgo de hipotensión severa, frecuentes (≥1/1000 y <1/100), dependiente de dosis y que se incrementa en hipovolemia o deshidratación.INTERVENCIÓN: se deriva al paciente a urgencias para valoración y se le cita para entregar carta de derivación al nefrólogo con el que tiene revisión en unos días.RESULTADO: el médico valora los PRM indicados y realiza los siguientes cambios: Rifamixina: 1/8 h los primeros 7 días de cada mesFurosemida: 1.5/24h (1-0.5-0) Metamizol: se sustituye por tramadol 37.5 mg/ paracetamol 325 mg 1/12 hCleboprida 500 mcg/ simeticona 200 mg: 1/8 h si dolor abdominal Además, el médico indica seguimiento de presión arterial en la farmacia comunitaria. Tras los cambios la paciente se encuentra mejor y sus valores de presión arterial se han normalizado con una media PAS/PAD 13/7 (mmHg) FC 72 ppm. (AU)

Impact of two sport education units on learning outcomes in primary school / Impacto de dos unidades didácticas de educación deportiva sobre objetivos de aprendizaje en educación primaria / Impacto de dúas unidades didáticas de educação esportiva nos objetivos de aprendizagem do ensino fundamental

The purposes of the study were (a) to explore the effect of two-Sport Education units (basketball and floorball) on game performance and game knowledge of Primary Education students according to their skill level, and (b) to know whether there were differences according to the sport taught (basketball and floorball). The participants were 33 students from two primary school classes. This study followed a mixed-methods approach. Quantitative data were obtained through a cuasi-experimental pretest-posttest design. Qualitative data were obtained after the intervention. Two teaching units (basketball and floorball) were applied in two different classes, one class experienced the basketball unit and the other the floorball unit and vice versa. We analysed game performance variables (decision making, skill execution, game performance, game involvement) and game knowledge. Students' performance was also measured using qualitative data which were collected through two methods: (a) experts' analysis on game performance of students, and (b) students' and teacher's perception of students´ performance with Sport Education. The results were affected both the sport taught and the skill level of students. The teacher emphasized that it was very complex for the primary students to understand some tactical and technical concepts, especially in floorball. At the primary level, student previous experience with the content and skill level conditioned the results in the variables related with game performance and knowledge. It is suggested that enacting Sport Education units of invasion games with implement such as floorball, at the primary level, might require more explicit instruction and longer teaching units in order to guarantee a minimum level of technical and tactical improvement. (AU)

Los objetivos del estudio fueron: (a) explorar el efecto de dos unidades didácticas de educación deportiva (baloncesto y floorball) sobre el rendimiento de juego y el conocimiento de alumnado de educación primaria, de acuerdo con su nivel de habilidad, y (b) conocer si hubo diferencias de acuerdo con el deporte (baloncesto y floorball). Los participantes fueron 33 alumnos de dos clases de educación primaria. Este estudio siguió un enfoque de métodos mixtos. Los datos cuantitativos se obtuvieron mediante un diseño cuasi-experimental pretest-postest. Los datos cualitativos se obtuvieron después de la intervención. Se aplicaron dos unidades didácticas (baloncesto y floorball) en dos clases diferentes, una clase experimentó la unidad de baloncesto y la otra la de floorball y viceversa. Se analizaron variables relacionadas con el rendimiento de juego (toma de decisión, ejecución técnica, rendimiento de juego, implicación en el juego) y el conocimiento. Los resultados de aprendizaje del alumnado fueron también analizados utilizando datos cualitativos del: (a) análisis realizado por expertos y (b) la percepción de los propios alumnos y el maestro. Los resultados fueron afectados por el deporte enseñado y el nivel de habilidad del alumnado. El maestro enfatizó que fue complejo para el alumnado de primaria comprender determinados conceptos tácticos y técnicos, especialmente en floorball. En educación primaria, la experiencia previa del alumnado con el contenido y el nivel de habilidad condicionó los resultados de las variables relacionadas con el rendimiento de juego y el conocimiento. Se sugiere que las unidades didácticas basadas en el modelo de educación deportiva en deportes de invasión con implemento, como ocurre en floorball en educación primaria, podría requerir de una instrucción más concreta y unidades didácticas más largas con el fin de garantizar un nivel mínimo de aprendizaje técnico y táctico. (AU)

Os objetivos do estudo foram: (a) explorar o efeito de duas unidades didáticas de educação esportiva (basquete e floorball) no desempenho de jogo e no conhecimento de alunos do ensino fundamental, de acordo com seu nível de habilidade, e (b) saber se houve diferenças de acordo com o esporte (basquete e floorball). Os participantes foram 33 alunos de duas turmas do ensino fundamental. Este estudo seguiu uma abordagem de métodos mistos. Os dados quantitativos foram obtidos por meio de um desenho pré-teste-pós-teste quase experimental. Os dados qualitativos foram obtidos após a intervenção. Duas unidades didáticas (basquete e floorball) foram aplicadas em duas turmas distintas, uma aula experimentou a unidade de basquete e a outra a unidade de floorball e vice-versa. Variáveis relacionadas ao desempenho do jogo (tomada de decisão, execução técnica, desempenho do jogo, envolvimento no jogo) e conhecimento foram analisadas. Os resultados de aprendizagem dos alunos também foram analisados com base em dados qualitativos de: (a) análise realizada por especialistas e (b) a percepção dos próprios alunos e do professor. Os resultados foram afetados pelo esporte ensinado e pelo nível de habilidade dos alunos. O professor enfatizou que foi difícil para os alunos do ensino fundamental entender alguns conceitos táticos e técnicos, principalmente no floorball. No ensino fundamental, a experiência prévia dos alunos com o conteúdo e o nível de habilidade condicionou os resultados das variáveis relacionadas ao desempenho e conhecimento do jogo. Sugere-se que a utilização de unidades didáticas baseadas no modelo de educação esportiva em esportes de invasão com implemento, como ocorre no floorball no ensino fundamental, poderia exigir instrução mais específica e unidades didáticas mais longas para garantir um nível mínimo de aprendizagem técnico e tático. (AU)

Role of hormones in sarcopenia.

Aging involves numerous changes in body composition that include a decrease in skeletal muscle mass. The gradual reduction in muscle mass is associated with a simultaneous decrease in muscle strength, which leads to reduced mobility, fragility and loss of independence. This process called sarcopenia is secondary to several factors such as sedentary lifestyle, inadequate nutrition, chronic inflammatory state and neurological alterations. However, the endocrine changes associated with aging seem to be of special importance in the development of sarcopenia. On one hand, advancing age is associated with a decreased secretion of the main hormones that stimulate skeletal muscle mass and function (growth hormone, insulin-like growth factor 1 (IGFI), testosterone and estradiol). On the other hand, the alteration of the IGF-I signaling along with decreased insulin sensitivity also have an important impact on myogenesis. Other hormones that decline with aging such as the adrenal-derived dehydroepiandrosterone, thyroid hormones and vitamin D seem to also be involved in sarcopenia. Adipokines released by adipose tissue show important changes during aging and can affect muscle physiology and metabolism. In addition, catabolic hormones such as cortisol and angiotensin II can accelerate aged-induced muscle atrophy, as they are involved in muscle wasting and their levels increase with age. The role played by all of these hormones and the possible use of some of them as therapeutic tools for treating sarcopenia will be discussed.

Climate change vulnerability of confined livestock systems predicted using bioclimatic indexes in an arid region of México.

Climate change is a major world-wide challenge to livestock production because food security is likely to be compromised by increased heat stress of the animals. The objective of this study was to characterize, using bioclimatic indexes, two livestock regions located in an arid zone of México, and to use this information to predict the impact of global warming on animal production systems of these regions located in the state of Baja California (México). A 5-year database (i.e., 2011 to 2015) consisting of about one million data points from two zones (i.e., coast, valley) from four meteorological stations in the north of Baja California were used. Bioclimatic indexes were constructed for the four types of livestock production systems most common in this region, being: dairy cattle, beef cattle, sheep, pigs. The temperature-humidity index (THI) thresholds used to classify heat stress were determined and scaled for each livestock species as: THIbeef and THIpig 74 units; THImilk 72 units; and THIsheep 23 units. Statistical differences between indices were detected (P < 0.01) during summer for the valley and coast zones as (THIbeef = 72.9 and 51.8; THImilk = 80.6 and 67.4; THIpigs = 83.9 and 65.2; THIsheep = 29.5 and 20.1 units). Coast zone weather did not suggest vulnerability of livestock production systems to heat stress at any time of the year, but heat stress risk during summer for valley zone dairy cattle, sheep and pigs was classified as severe, but lower for feedlot cattle. Prediction models showed significant adjustment just in the coastal zone for THImilk, THIsheep, and THIsheep, suggesting more impact of global warming during summer in the coastal zone. Use of management strategies to reduce heat load of domestic animals during summer in northern Baja California is essential to maintain their productivity, with more emphasis in the valley zone.

Efficacy and Safety of Up-dosing Antihistamines in Chronic Spontaneous Urticaria: A Systematic Review of the Literature.

BACKGROUND AND OBJECTIVES: According to current guidelines, oral antihistamines are the first-line treatment for chronic spontaneous urticaria (CSU). Up-dosing antihistamines to 4-fold the licensed dose is recommended if control is not achieved. Such indications are based mainly on expert opinion. Objectives: To critically review and analyze clinical evidence on the efficacy and safety of higher-than-licensed dosage of second-generation oral antihistamines in the treatment of CSU. MATERIAL AND METHODS: A systematic literature review was performed following a sensitive search strategy. All articles published in PubMed, EMBASE, and the Cochrane Library between 1961 and October 2018 were examined. Publications with CSU patients prescribed secondgeneration antihistamines in monotherapy compared with placebo, licensed dosages, and/or higher dosages were included. Articles were evaluated by peer reviewers. Quality was evaluated using the Jadad and Oxford scores. RESULTS: We identified 337 articles, of which 14 were included in the final evaluation (fexofenadine, 6; cetirizine, 2; levocetirizine and desloratadine, 1; levocetirizine, 1; rupatadine, 2; ebastine, 1; and bilastine, 1). Only 5 studies were placebo-controlled. The number of patients included ranged from 20 to 439. The observation lapse was ≤16 weeks. High fexofenadine doses produced a significant dosedependent response and controlled urticaria in most patients. Cetirizine, levocetirizine, rupatadine, and bilastine were more effective in up-dosing. The most frequent adverse events were headache and drowsiness. CONCLUSION: The low quality and heterogeneity of the articles reviewed made it impossible to reach robust conclusions and reveal the need for large-scale randomized clinical trials.