Synthesis of 6ß-hydroxy androgens from a 3,5-diene steroid precursor to test for cytochrome P450 3A4-catalyzed hydroxylation of androstenedione.

6ß-Hydroxytestosterone is a biomarker for the activity of human cytochrome P450 3A4 (P450 3A4), the major drug metabolizing cytochrome P450 enzyme. Despite its significance, efficient routes for the chemical synthesis of 6ß-hydroxytestosterone are rare. In this study, 6ß-hydroxytestosterone was synthesized through the oxidation of a 3,5-diene precursor under the Uemura-Doyle reaction conditions using a dirhodium catalyst in the presence of tert-butylhydroperoxide. Mechanistic studies showed that some oxygen is incorporated from molecular oxygen and CH abstraction is partially rate-limiting. This reaction was used to synthesize 6ß-hydroxyandrostenedione, which was used as a standard to test the hypothesis of whether P450 3A4 catalyzes the hydroxylation of androstenedione. Upon incubation of P450 3A4 with androstenedione, a hydroxylated product was formed, which matched the retention time of synthetic 6ß-hydroxyandrostenedione. This reaction can be exploited to study other biochemical processes involving compounds with a 6 ß -hydroxy-3-keto-Δ4 steroid backbone.

Whole-Exome Sequencing, Proteome Landscape, and Immune Cell Migration Patterns in a Clinical Context of Menkes Disease.

Menkes disease (MD) is a rare and often lethal X-linked recessive syndrome, characterized by generalized alterations in copper transport and metabolism, linked to mutations in the ATPase copper transporting α (ATP7A) gene. Our objective was to identify genomic alterations and circulating proteomic profiles related to MD assessing their potential roles in the clinical features of the disease. We describe the case of a male patient of 8 months of age with silvery hair, tan skin color, hypotonia, alterations in neurodevelopment, presence of seizures, and low values of plasma ceruloplasmin. Trio-whole-exome sequencing (Trio-WES) analysis, plasma proteome screening, and blood cell migration assays were carried out. Trio-WES revealed a hemizygous change c.4190C > T (p.S1397F) in exon 22 of the ATP7A gene. Compared with his parents and with child controls, 11 plasma proteins were upregulated and 59 downregulated in the patient. According to their biological processes, 42 (71.2%) of downregulated proteins had a participation in cellular transport. The immune system process was represented by 35 (59.3%) downregulated proteins (p = 9.44 × 10-11). Additional studies are necessary to validate these findings as hallmarks of MD.

Hydrological and topographic determinants of biomass and species richness in a Mediterranean-climate shrubland.

BACKGROUND: In arid and semiarid shrublands, water availability directly influences ecosystem properties. However, few empirical tests have determined the association between particular soil and hydrology traits with biodiversity and ecosystem biomass at the local scale. METHODS: We tested if plant species richness (S) and aboveground biomass (AGB) were associated with soil and topographic properties on 36 plots (ca. 12.5 m2) in 17 hectares of chaparral in the Mediterranean-climate of Valle de Guadalupe, Baja California, México. We used close-to-the-ground aerial photography to quantify sky-view cover per species, including all growth forms. We derived an elevation model (5 cm) from other aerial imagery. We estimated six soil properties (soil water potential, organic matter content, water content, pH, total dissolved solids concentration, and texture) and four landscape metrics (slope, aspect, elevation, and topographic index) for the 36 plots. We quantified the biomass of stems, leaves, and reproductive structures, per species. RESULTS: 86% of AGB was in stems, while non-woody species represented 0.7% of AGB but comprised 38% of S (29 species). Aboveground biomass and species richness were unrelated across the landscape. S was correlated with aspect and elevation (R = 0.53, aspect P = 0.035, elevation P = 0.05), while AGB (0.006-9.17 Kg m-2) increased with soil water potential and clay content (R = 0.51, P = 0.02, and P = 0.04). Only three species (11% of total S) occupied 65% of the total plant cover, and the remaining 26 represented only 35%. Cover was negatively correlated with S (R = -0.38, P = 0.02). 75% of AGB was concentrated in 30% of the 36 plots, and 96% of AGB corresponded to only 20% of 29 species. DISCUSSION: At the scale of small plots in our studied Mediterranean-climate shrubland in Baja California, AGB was most affected by soil water storage. AGB and cover were dominated by a few species, and only cover was negatively related to S. S was comprised mostly by uncommon species and tended to increase as plant cover decreased.

Fatigue Increases in Resting Muscle Oxygen Consumption after a Women's Soccer Match.

Currently, near infrared spectroscopy has a clear potential to explain the mechanisms of fatigue by assessing muscle oxygenation. The objective of the study was to observe the changes in muscle oxygen consumption after an official women's soccer match. The sample was 14 players who competing in the second division of Spain of women's soccer. They were evaluated before, immediately after and 24 h after the official match. Biochemical parameters were measured in blood plasma (BUN, GOT, LDH, CPK). The jumping in countermovement, perceived exertion and perceived muscle pain were also assessed. The muscle oxygen consumption and muscle oxygen saturation were evaluated in the gastrocnemius muscle with an arterial occlusion test. ANOVA of repeated measures, Pearson's correlation and Hopkins' statistics were applied to measure the magnitudes of change and effect size. There was observed an increase in kinetics of SmO2 at 24 h after the official match, using arterial occlusion. In addition, it was found that the increase in muscle oxygenation correlated with fatigue indicators, such as the increases in LDH, perceived muscle pain and the decrease in countermovement. It is confirmed that a women's soccer match produced an increase of resting muscle oxygenation in 24 h after the official match.

Un estudio sobre la precariedad laboral en enfermería: consecuencias y relaciones en torno al síndrome de agotamiento y el abandono profesional / A study about precarious work in nursing: consequences and relationships around the syndrome of burnout and professional abandonment

Los profesionales de enfermería constituyen cuantitativamente la mayor fuerza de trabajo en los sistemas de salud de casi todos los países del mundo, sin embargo, el índice de abandono de la profesión es importante, un problema que merece encontrar soluciones. Muchos son los motivos que se han esgrimido para ello, pero entre los que menos han sido estudiados, estarían algunas relaciones contractuales precarias que se dan en España y que no parecen estar en sintonía con las recomendaciones internacionales sobre la calidad en el trabajo enfermero. Objetivo: la posible existencia de una relación entre este tipo de contratos con el agotamiento profesional y, en caso positivo, con una posible afectación de la vida cotidiana que redunde en la satisfacción laboral y en la posibilidad del abandono laboral constituye el objetivo principal de este estudio. Método: para ello, se ha llevado a cabo un estudio observacional, descriptivo y transversal sobre una muestra de 216 enfermeros con experiencia en contratos precarios denominados tipo "Pool"/"volante". Los cuestionarios utilizados fueron el Maslach Burnout Inventory, para evaluar el síndrome de agotamiento profesional, y un cuestionario de elaboración propia consistente en 8 preguntas sociodemográficas y sobre aspectos de su vida cotidiana que pudieran tener relación con el abandono laboral. Resultados: la muestra estudiada posee un nivel medio en la escala de agotamiento emocional con 23,3 puntos [desviación típica = 11,42], un nivel elevado en la escala de despersonalización con 10,70 puntos [6,33] y un nivel elevado de realización personal con 31,63 puntos [9,25]. Conclusiones: los resultados de este estudio concluyen que los profesionales con relaciones contractuales "Pool"/"volante" presentan un nivel medio-elevado de agotamiento profesional. A su vez se han podido observar asociaciones estadísticamente significativas entre puntuaciones elevadas en las diferentes esferas del síndrome y aspectos de la vida personal de los enfermeros estudiados, lo que estaría influyendo en los sentimientos de insatisfacción personal y aumentando las posibilidades de incidencia sobre el abandono profesional

Nursing professionals are quantitatively the largest workforce in the health systems of almost all countries in the world however, the rate of abandonment of the profession is important problem that deserves to find solutions. There are many reasons for this, but among those that have been least studied, there would be some precarious contractual relationships that occur in Spain and do not seem to be in line with international recommendations on quality in nursing work. Objective: the possible existence of a relationship between this type of contract with syndrome of burnout and, in a positive case, with a possible impact on daily life, that results in job satisfaction and the possibility of leaving the workplace, is the main objective of this study Method: to this end, an observational, descriptive and cross-sectional study was carried out on a sample of 216 nurses with experience in precarious contracts called "Pool" / "volante", type. The questionnaires used were the Maslach Burnout Inventory, to evaluate the syndrome of professional exhaustion, and a self-prepared questionnaire consisting of 8 sociodemographic questions and aspects of their daily life that may be related to the abandonment of work. Results: the sample studied has an middle level on the emotional exhaustion scale with 23.3 points [standard deviation = 11.42], a high level on the depersonalization scale with 10.70 points[6.33] and a high level of personal achievement with 31.63 points[9.25]. Conclusions: the results of this study conclude that professionals with contractual relations "Pool" / "volante", present a medium-high level of professional exhaustion. At the same time, statistically significant associations have been observed between high scores in the different spheres of the syndrome and aspects of the personal life of the nurses studied, which would be influencing the feelings of personal dissatisfaction and increasing the possibilities of incidence on professional abandonment

Analytical validation and reference intervals for freezing point depression osmometer measurements of urine osmolality in dogs.

Urine osmolality (UOsm) is considered the most accurate measure of urine concentration and is used to assess body fluid homeostasis and renal function. We performed analytical validation of freezing point depression measurement of canine UOsm, to establish reference intervals (RIs) and to determine the effect of age, sex, and reproductive status on UOsm in dogs. Clinically healthy dogs ( n = 1,991) were retrospectively selected and stratified in groups by age (young [0-12 mo], adults [13-84 mo], and seniors [>84 mo]), sex (females and males), and reproductive status (intact and neutered). RIs were calculated for each age group. Intra- and inter-assay coefficients of variation were <1% in all cases. Good linearity ( r2 = 1, p < 0.001) and recovery (89-98%) were observed. The limit of detection and limit of quantification were zero. Urine specific gravity and UOsm had a highly significant positive correlation ( r = 0.96, p < 0.001) but had inconsistent agreement. The 95% RI for canine UOsm was 369-2,416 mOsm/kg in young and adult dogs, and 366-2,178 mOsm/kg in seniors. Senior dogs had a significantly lower UOsm than young and adult dogs ( p < 0.000). Neutered females had a significantly lower UOsm than intact female dogs ( p < 0.002). These results indicate that the method evaluated is adequate for UOsm measurement and that RIs based on age and reproductive status should be used in dogs.