Evaluation of Zonulin Expression and Its Potential Clinical Significance in Glioblastoma.

Glioblastoma, the deadliest adult brain tumor, poses a significant therapeutic challenge with a dismal prognosis despite current treatments. Zonulin, a protein influencing tight junctions and barrier functions, has gained attention for its diverse roles in various diseases. This study aimed to preliminarily analyze the circulating and tumor zonulin levels, evaluating their impact on disease prognosis and clinical-radiological factors. Additionally, we investigated in vitro zonulin expression in different glioblastoma cell lines under two different conditions. The study comprised 34 newly diagnosed glioblastoma patients, with blood samples collected before treatment for zonulin and haptoglobin analysis. Tumor tissue samples from 21 patients were obtained for zonulin expression. Clinical, molecular, and radiological data were collected, and zonulin protein levels were assessed using ELISA and Western blot techniques. Furthermore, zonulin expression was analyzed in vitro in three glioblastoma cell lines cultured under standard and glioma-stem-cell (GSC)-specific conditions. High zonulin expression in glioblastoma tumors correlated with larger preoperative contrast enhancement and edema volumes. Patients with high zonulin levels showed a poorer prognosis (progression-free survival [PFS]). Similarly, elevated serum levels of zonulin were associated with a trend of shorter PFS. Higher haptoglobin levels correlated with MGMT methylation and longer PFS. In vitro, glioblastoma cell lines expressed zonulin under standard cell culture conditions, with increased expression in tumorsphere-specific conditions. Elevated zonulin levels in both the tumor and serum of glioblastoma patients were linked to a poorer prognosis and radiological signs of increased disruption of the blood-brain barrier. In vitro, zonulin expression exhibited a significant increase in tumorspheres.

Androgen deficiency is associated with a better prognosis in glioblastoma.

BACKGROUND: The androgen receptor (AR) has been demonstrated to play a role in the pathogenesis of glioblastoma; however, the implications of circulating testosterone levels in the biology of glioblastoma remain unknown. AIM: This study aimed to analyze the association between circulating testosterone levels and the prognosis of patients with glioblastoma. METHODS: Forty patients with primary glioblastoma were included in the study. The main prognostic endpoint was progression-free survival (PFS). Circulating testosterone levels were used to determine the state of androgen deficiency (AD). AR expression was analyzed by reverse-transcriptase polymerase chain reaction, Western blot, and immunofluorescence. Survival analysis was performed using the log-rank test and univariate and multivariate Cox regression analysis. RESULTS: Most of the patients showed AR expression, and it was mainly located in the cytoplasm, as well as in the nucleus of tumor cells. Patients with AD presented a better PFS than those patients with normal levels (252.0 vs. 135.0 days; p = 0.041). Furthermore, normal androgenic status was an independent risk factor for progression in a multivariate regression model (hazard ratio = 6.346; p = 0.004). CONCLUSION: Circulating testosterone levels are associated with the prognosis of glioblastoma because patients with AD show a better prognosis than those with normal androgenic status.

Pocillopora damicornis-associated macroinvertebrate responses to spatial gradients in the southern Mexican Pacific.

We explicitly tested for spatial changes in Pocillopora damicornis-associated invertebrates across several spatial scales in the southern Mexican Pacific. Sorting of invertebrates from 40 coral heads along 882 km of the coast yielded 325 taxa, 283% more than any other Pocillopora spp. coral host study to date, but estimators signals that richness might be 17-39% larger than the current number. Permutation, ordination, and regression analysis indicate that the composition and abundance of invertebrates vary in response to the spatial distance among coral heads: high similarity and variation occur among coral heads within localities (<500 m), probably related to faunal homogenization, but progressively modest reduction in similarity and variation as spatial distance increases suggesting a weak role for environmental sorting across southern Mexican Pacific coral reefs. Future studies should explicitly explore spatial, environmental, and historical biogeography processes that regulate and maintain community structure and biodiversity on eastern Pacific reefs.

Copper(II) Affects the Biochemical Behavior of Proinsulin C-peptide by Forming Ternary Complexes with Serum Albumin.

Peptide hormones are essential signaling molecules with therapeutic importance. Identifying regulatory factors that drive their activity gives important insight into their mode of action and clinical development. In this work, we demonstrate the combined impact of Cu(II) and the serum protein albumin on the activity of C-peptide, a 31-mer peptide derived from the same prohormone as insulin. C-peptide exhibits beneficial effects, particularly in diabetic patients, but its clinical use has been hampered by a lack of mechanistic understanding. We show that Cu(II) mediates the formation of ternary complexes between albumin and C-peptide and that the resulting species depend on the order of addition. These ternary complexes notably alter peptide activity, showing differences from the peptide or Cu(II)/peptide complexes alone in redox protection as well as in cellular internalization of the peptide. In standard clinical immunoassays for measuring C-peptide levels, the complexes inflate the quantitation of the peptide, suggesting that such adducts may affect biomarker quantitation. Altogether, our work points to the potential relevance of Cu(II)-linked C-peptide/albumin complexes in the peptide's mechanism of action and application as a biomarker.

Characterizing metal-biomolecule interactions by mass spectrometry.

Metal micronutrients are essential for life and exist in a delicate balance to maintain an organism's health. The labile nature of metal-biomolecule interactions clouds the understanding of metal binders and metal-mediated conformational changes that are influential to health and disease. Mass spectrometry (MS)-based methods and technologies have been developed to better understand metal micronutrient dynamics in the intra- and extracellular environment. In this review, we describe the challenges associated with studying labile metals in human biology and highlight MS-based methods for the discovery and study of metal-biomolecule interactions.

Deep-sea Ophiuroidea (Echinodermata) collected during the TALUD cruises in western Mexico.

Deep-sea ophiuroids from western Mexico have been documented since 1899, but mostly by non-Mexican expeditions. TALUD is a Mexican project designed to study the deep-sea fauna from Mexico. As part of it, the present contribution provides for the first time detailed information about the taxonomy and distribution, as well as images, of deep-sea ophiuroids from western Mexico, representing a useful taxonomic identification tool for Ophiuroidea from the eastern Pacific. A total of 38 species of ophiuroid (35 identified at species level, one at genus level, and two as confer) were collected from 83 stations located at 123‒2,309 m depth. At a regional scale, several new species records are presented: six for western Baja California, five for western Baja California Sur, two for the Gulf of California, four for Jalisco, 14 for Colima, and five for Guerrero. Geographic (six) and bathymetric (seven) distribution ranges of species are extended. An updated list of deep-sea ophiuroids (61 species) from western Mexico is provided together with an identification key to species collected during this survey. In addition, nine records of deep-sea ophiuroids for the Mexican Pacific are unproven, doubtful or invalid. We corroborated the presence of Ophiacantha eurypoma and Ophiacantha pacifica in the study area and added Amphiura gymnogastra as the first record for Mexico. We propose to transfer Ophiacantha phragma to Ophiolimna on account of it having both granules and spines on the dorsal disc and striated arm plates. TALUD cruises collected 57 % of the total deep-sea species known to occur off Mexico, making it the most important survey of deep-sea Ophiuroidea carried out in western Mexico to date.

Angiogenic biomarkers for the follow-up of singleton pregnancies with suspected preeclampsia.

BACKGROUND: Preeclampsia (PE) is a hypertensive disorder of pregnancy and one of the leading causes of maternal and fetal morbidity and mortality worldwide. While the underlying cause of remains unknown, abnormal placentation in early stages of pregnancy is thought to be a main triggering event for the more severe and early-onset forms. A consequence of placental insufficiency is an imbalance of angiogenic factors in the maternal circulation. The objective was to assess the utility of the angiogenic biomarker sFlt-1/PlGF for the diagnosis, follow-up and prognosis of preeclampsia. METHODS: This was a retrospective cohort study based including 65 consecutive singleton pregnancies with suspected preeclampsia referred to our hospital between January 2018 and February 2019. PE was defined as early-onset (20-33+6 weeks) and late-onset (≥34 weeks). The main independent variable was sFlt-1/PlGF classified in women with early or late onset PE, respectively, as low when <38 or <38, intermediate when 38-84 or 38-109, and high when ≥85 or ≥110. RESULTS: PE was confirmed in 14 (4 early-onset, 10 late-onset) of the participants. 122 sFlt-1/PIGF ratio determinations were requested. The optimal sFlt-1/PlGF to predict PE was ≥86 with a sensitivity of 93% and a specificity of 96% (AUC 0.95; CI 95% 0.90-1.0; P<0.001). A multilevel logistic model for the diagnosis of PE was adjusted for age, Body Mass Index, diabetes, proteinuria and mean arterial pressure. Women were 16.5 times (P=0.013) more likely to develop PE if they had intermediate sFlt-1/PlGF levels and 451 times (P<0.001) more likely if they had high biomarker levels compared to those with levels below 38. The probability of PE was 3.73 times (P=0.046) greater in those with maternal and/or fetal complications. CONCLUSIONS: The biomarker proved useful to diagnose PE and assess its prognosis. Patients diagnosed with PE had a higher frequency of complications and their newborns were of lower birth weight.

Competencias en ecografía clínica, una necesidad inaplazable para los cuidados intensivos / Skills in clinical ultrasound, an urgent need for intensive care

Introducción: la ecografía es una herramienta fundamental en la asistencia al paciente crítico. La incorporación de la ecografía clínica al trabajo de los intensivistas y emergencistas debe ser validada a través del desempeño; por tanto, se hace necesario el desarrollo de las competencias profesionales en este ámbito. Objetivo: exponer los elementos teóricos derivados del desarrollo científico-técnico que fundamentan las competencias en ecografía clínica. Métodos: se realizó un análisis crítico reflexivo sobre el contenido de la bibliografía revisada. Se accedió a libros y artículos científicos de revistas indexadas en las bases de datos PubMed, Scopus, Medscape, SciELO, y Medline, fueron seleccionados 25 artículos científicos con suficiente calidad y actualidad, en su mayoría, de los últimos cinco años y pertinentes para el estudio. Se utilizaron las palabras claves: ecografía clínica, competencias, cuidados intensivos, ultrasonido de urgencia y educación médica. Desarrollo: la ausencia del enfoque por competencias en la enseñanza y aprendizaje de la ecografía clínica constituye una barrera para lograr la generalización de esta técnica en las unidades de cuidados intensivos y áreas de emergencias. La introducción de la ecografía clínica en cuidados intensivos debe tener un enfoque de educación basada en competencias en la educación de pregrado y posgrado con un programa estructurado, certificado y validado por los estándares internacionales. Conclusiones: es imprescindible que se universalice y haga sostenible la utilidad y necesidad de este enfoque, su realización y continuidad en el tiempo, a través de la educación permanente y continuada.

Introduction: ultrasound is a fundamental tool in critical patient care. The incorporation of clinical ultrasound into the work of intensivists and emergencies must be validated through performance; therefore, it is necessary to develop professional skills in this area. Objective: to present the theoretical elements derived from the scientific-technical development that support the competencies in clinical ultrasound. Methods: a reflective critical analysis was carried out on the content of the reviewed bibliography. Books and scientific articles from journals indexed in the PubMed, Scopus, Medscape, SciELO, and Medline databases were accessed, 25 scientific articles were selected with sufficient quality and topicality, mostly from the last five years and with relevance in the study. The keywords were used: clinical ultrasound, skills, intensive care, emergency ultrasound and medical education. Development: the absence of the competency-based approach in the teaching and learning of clinical ultrasound constitutes a barrier to achieve the generalization of this technique in intensive care units and emergency areas. The introduction of clinical ultrasound in intensive care must have a competency-based education approach in undergraduate and postgraduate education with a structured program, certified and validated by international standards. Conclusions: it is essential that the usefulness and necessity of this approach, its implementation and continuity over time, be universalized and made sustainable through permanent and continuous education.

Differences in the Second Coordination Sphere Tailor the Substrate Specificity and Reactivity of Thiol Dioxygenases.

In recent years, considerable progress has been made toward elucidating the geometric and electronic structures of thiol dioxygenases (TDOs). TDOs catalyze the conversion of substrates with a sulfhydryl group to their sulfinic acid derivatives via the addition of both oxygen atoms from molecular oxygen. All TDOs discovered to date belong to the family of cupin-type mononuclear nonheme Fe(II)-dependent metalloenzymes. While most members of this enzyme family bind the Fe cofactor by two histidines and one carboxylate side chain (2-His-1-carboxylate) to provide a monoanionic binding motif, TDOs feature a neutral three histidine (3-His) facial triad. In this Account, we present a bioinformatics analysis and multiple sequence alignment that highlight the significance of the secondary coordination sphere in tailoring the substrate specificity and reactivity among the different TDOs. These insights provide the framework within which important structural and functional features of the distinct TDOs are discussed.The best studied TDO is cysteine dioxygenase (CDO), which catalyzes the conversion of cysteine to cysteine sulfinic acid in both eukaryotes and prokaryotes. Crystal structures of resting and substrate-bound mammalian CDOs revealed two surprising structural motifs in the first- and second coordination spheres of the Fe center. The first is the presence of the abovementioned neutral 3-His facial triad that coordinates the Fe ion. The second is the existence of a covalent cross-link between the sulfur of Cys93 and an ortho carbon of Tyr157 (mouse CDO numbering scheme). While the exact role of this cross-link remains incompletely understood, various studies established that it is needed for proper substrate Cys positioning and gating solvent access to the active site. Intriguingly, bacterial CDOs lack the Cys-Tyr cross-link; yet, they are as active as cross-linked eukaryotic CDOs.The other known mammalian TDO is cysteamine dioxygenase (ADO). Initially, it was believed that ADO solely catalyzes the oxidation of cysteamine to hypotaurine. However, it has recently been shown that ADO additionally oxidizes N-terminal cysteine (Nt-Cys) peptides, which indicates that ADO may play a much more significant role in mammalian physiology than was originally anticipated. Though predicted on the basis of sequence alignment, site-directed mutagenesis, and spectroscopic studies, it was not until last year that two crystal structures, one of wild-type mouse ADO (solved by us) and the other of a variant of nickel-substituted human ADO, finally provided direct evidence that this enzyme also features a 3-His facial triad. These structures additionally revealed several features that are unique to ADO, including a putative cosubstrate O2 access tunnel that is lined by two Cys residues. Disulfide formation under conditions of high O2 levels may serve as a gating mechanism to prevent ADO from depleting organisms of Nt-Cys-containing molecules.The combination of kinetic and spectroscopic studies in conjunction with structural characterizations of TDOs has furthered our understanding of enzymatic sulfhydryl substrate regulation. In this article, we take advantage of the fact that the ADO X-ray crystal structures provided the final piece needed to compare and contrast key features of TDOs, an essential family of metalloenzymes found across all kingdoms of life.

Impulsivity is longitudinally associated with healthy and unhealthy dietary patterns in individuals with overweight or obesity and metabolic syndrome within the framework of the PREDIMED-Plus trial.

BACKGROUND: Few studies have analyzed the associations between impulsivity and dietary patterns. Some of them have shown a cross-sectional inverse relationship between impulsivity and healthy diet scores, whereas others reported a positive association with unhealthy dietary assessments. We aimed to examine longitudinal associations of impulsivity trait with adherence to healthy and unhealthy dietary patterns in older participants at high risk of cardiovascular disease over 3 years of follow-up. METHODS: A 3-year prospective cohort analysis within the PREDIMED-Plus-Cognition study conducted in 4 PREDIMED-Plus study centers was performed. The PREDIMED-Plus study aimed to test the beneficial effect of a lifestyle intervention on the primary prevention of cardiovascular disease. The participants with overweight or obesity and metabolic syndrome included in the present study (n = 462; mean age of 65.3 years; 51.5% female) completed both the UPPS-P Impulsive Behavior Scale (range: 0-236 points) and the 143-item Food Frequency Questionnaire at baseline, 1-year and 3-years of follow-up. Ten diet scores assessing healthy and unhealthy dietary patterns were evaluated. Linear mixed models were performed adjusting by several confounders to study the longitudinal associations between impulsivity trait and adherence to dietary pattern scores over 3 years of follow-up (also assessing interactions by sex, age, and intervention group). RESULTS: Impulsivity were negatively associated with adherence to the Healthy Plant-Based [ß = -0.92 (95%CI -1.67, -0.16)], Mediterranean [ß = -0.43 (95%CI -0.79, -0.07)], Energy-Restricted Mediterranean [ß = -0.76 (95%CI -1.16, -0.37)], Alternative Healthy Eating Index [ß = -0.88 (95%CI -1.52, -0.23)], Portfolio [ß = -0.57 (95%CI -0.91, -0.22)], and DASH [ß = -0.50 (95%CI -0.79, -0.22)] diet scores over 3 years of follow-up, whereas impulsivity was positively related with adherence to the unhealthy Western diet [ß = 1.59 (95%CI 0.59, 2.58)] over time. An interaction by intervention group was found, with those participants in the intervention group with high impulsivity levels having lower adherence to several healthy dietary patterns. CONCLUSIONS: Heightened impulsivity was longitudinally associated with lower adherence to healthy dietary patterns and higher adherence to the Western diet over 3 years of follow-up. Furthermore, nutritional intervention programs should consider impulsivity as a relevant factor for the intervention success. TRIAL REGISTRATION: Name of registry: Effect of an energy-restricted Mediterranean diet, physical activity and behavioral intervention on the primary prevention of cardiovascular disease. TRIAL REGISTRATION NUMBER: ISRCTN 89,898,870. Date of registration: 05/28/2014.

FKBP51, AmotL2 and IQGAP1 Involvement in Cilastatin Prevention of Cisplatin-Induced Tubular Nephrotoxicity in Rats.

The immunophilin FKBP51, the angiomotin AmotL2, and the scaffoldin IQGAP1 are overexpressed in many types of cancer, with the highest increase in leucocytes from patients undergoing oxaliplatin chemotherapy. Inflammation is involved in the pathogenesis of nephrotoxicity induced by platinum analogs. Cilastatin prevents renal damage caused by cisplatin. This functional and confocal microscopy study shows the renal focal-segmental expression of TNFα after cisplatin administration in rats, predominantly of tubular localization and mostly prevented by co-administration of cilastatin. FKBP51, AmotL2 and IQGAP1 protein expression increases slightly with cilastatin administration and to a much higher extent with cisplatin, in a cellular- and subcellular-specific manner. Kidney tubule cells expressing FKBP51 show either very low or no expression of TNFα, while cells expressing TNFα have low levels of FKBP51. AmotL2 and TNFα seem to colocalize and their expression is increased in tubular cells. IQGAP1 fluorescence increases with cilastatin, cisplatin and joint cilastatin-cisplatin treatment, and does not correlate with TNFα expression or localization. These data suggest a role for FKBP51, AmotL2 and IQGAP1 in cisplatin toxicity in kidney tubules and in the protective effect of cilastatin through inhibition of dehydropeptidase-I.

Oral Supplement Containing Hydroxytyrosol and Punicalagin Improves Dyslipidemia in an Adult Population without Co-Adjuvant Treatment: A Randomized, Double-Blind, Controlled and Crossover Trial.

Hydroxytyrosol (HT) and punicalagin (PC) exert cardioprotective and antiatherosclerotic effects. This study evaluated the effect of an oral supplement containing HT and PC (SAx) on dyslipidemia in an adult population. A randomized, double-blind, controlled, crossover trial was conducted over a 20-week period. SAx significantly reduced the plasma levels of triglycerides (TG) in subjects with hypertriglyceridemia (≥150 mg/dL) (from 200.67 ± 51.38 to 155.33 ± 42.44 mg/dL; p < 0.05), while no such effects were observed in these subjects after the placebo. SAx also significantly decreased the plasma levels of low-density lipoprotein cholesterol (LDL-C) in subjects with high plasma levels of LDL-C (≥160 mg/dL) (from 179.13 ± 16.18 to 162.93 ± 27.05 mg/dL; p < 0.01), while no such positive effect was observed with the placebo. In addition, the placebo significantly reduced the plasma levels of high-density lipoprotein cholesterol (HDL-C) in the total population (from 64.49 ± 12.65 to 62.55 ± 11.57 mg/dL; p < 0.05), while SAx significantly increased the plasma levels of HDL-C in subjects with low plasma levels of HDL-C (<50 mg/dL) (from 44.25 ± 3.99 to 48.00 ± 7.27 mg/dL; p < 0.05). In conclusion, the supplement containing HT and PC exerted antiatherosclerotic and cardio-protective effects by considerably improving dyslipidemia in an adult population, without co-adjuvant treatment or adverse effects.

Retrospective cohort study of laparoscopic ICG-Guided Lymphadenectomy in gastric cancer from a Western country center.

BACKGROUND: Indocyanine green (ICG) guided lymphadenectomy has been proposed has a technique to improve the lymphadenectomy of patients with gastric cancer. Nevertheless, experience with this procedure is scarce in Western countries. METHODS: A retrospective analytic study in a tertiary hospital in Spain was performed, comparing patients who underwent laparoscopic gastrectomy with (ICG cohort) and without (historic cohort) ICG guided lymphadenectomy. RESULTS: Thirty four patients were included (17 in each group). Although the number of positive nodes was similar in both groups (0.0 in the ICG cohort vs. 2 in the historic cohort, p = 0.119), the number of lymph nodes removed was higher in the ICG cohort (42.0 vs 28.0, p = 0.040). In the ICG cohort, more lymph nodes were positive for adenocarcinoma in the group of nodes that were positive for IGC (10.6% of the IGC + nodes vs. 1.9% in the ICG - nodes, p < 0.001). CONCLUSIONS: ICG lymphadenectomy is a promising procedure that could improve the lymphadenectomy of patients with gastric cancer. ICG lymphadenectomy could be used to increase the number of lymph nodes removed in patients with a high-risk of nodal invasion or it could be used to reduce the surgical aggressiveness in fragile patients with a low-risk of nodal invasion.

Decrease in Readmissions after Hospitalisation for COPD Exacerbation through a Home Care Model.

Objective: To decrease readmissions at 30 and 90 days post-discharge from a hospital admission for chronic obstructive pulmonary disease exacerbation (COPDE) through the home care model of the Ambulatory Chronic Respiratory Care Unit (ACRCU), increase patient survival at one year, and validate our readmission risk scale (RRS). Materials and methods: This was an observational study, with a prospective data collection and a retrospective data analysis. A total of 491 patients with a spirometry diagnosis of chronic obstructive pulmonary disease (COPD) requiring hospitalisation for an exacerbation were included in the study. Subjects recruited within the first year (204 cases) received conventional care (CC). In the following year a home care (HC) programme was implemented and of those recruited that year (287) 104 were included in the ACRCU, administered by a specialised nurse. Results: In the group of patients included in the home care model of the Ambulatory Chronic Respiratory Care Unit (ACRCU) a lower number of readmissions was observed at 30 and 90 days after discharge (30.5% vs. 50%, p = 0.012 and 47.7% vs. 65.2%, p = 0.031, respectively) and a greater one-year survival (85.3% vs. 59.1%, p < 0.001). The validation of our RRS revealed that the tool's capacity to predict readmissions at both 30 and 90 days was not high (AUC = 0.69 and AUC = 0.66, respectively). Conclusions: The inclusion of exacerbator or fragile COPD patients in the ACRCU could achieve a decrease in readmissions and an increase in survival. The number of episodes of exacerbation within the 12 months prior to the hospital admission is the variable that best predicts the risk of readmission.

Objetivo: Disminuir los reingresos a los 30 y 90 días tras el alta por un ingreso hospitalario por exacerbación de enfermedad pulmonar obstructiva crónica (EPOC) a través del modelo de atención domiciliaria de la Unidad de Cuidados Crónicos Respiratorios Ambulatorios (UCCRA), aumentar la supervivencia al año y validar nuestra escala de riesgo de reingreso (ERR). Material y métodos: Estudio observacional con recogida prospectiva de datos. Se incluyó en el estudio a un total de 491 pacientes con diagnóstico espirométrico de enfermedad pulmonar obstructiva crónica que requirieron hospitalización por una agudización. Los sujetos reclutados dentro del primer año (204 casos) recibieron atención convencional (AC). Al año siguiente se implementó un programa de atención domiciliaria (AD) y de los pacientes reclutados ese año (287), 104 fueron incluidos en la UCCRA con seguimiento de una enfermera especializada. Resultados: En el grupo de pacientes incluidos en el modelo de atención domiciliaria de la UCCRA se observó un menor número de reingresos a los 30 y 90 días tras el alta (30,5% vs 50%, p = 0,012 y 47,7% vs. 65,2%, p = 0,031, respectivamente) y una mayor supervivencia al año (85,3% vs. 59,1%, p < 0,001). La validación de nuestra ERR reveló que la capacidad de la misma para predecir reingresos tanto a los 30 como a los 90 días no era alta (AUC = 0,69 y AUC = 0,66, respectivamente). Conclusiones: La inclusión de pacientes con EPOC agudizadores o frágiles en la UCCRA podría conseguir una disminución de los reingresos y una aumento de la supervivencia. El número de agudizaciones en los 12 meses previos al ingreso hospitalario es la variable que mejor predice el riesgo de reingreso.

A morphological and morphometric approach to study Ophiuroidea (Echinodermata): Size changes of Ophiocomella alexandri.

Studies on size changes of Ophiuroidea are limited, despite their importance and implications in taxonomy, phylogenetics, ecology, and distribution. These studies have traditionally been based on descriptive size series seldom integrating quantitative analyses to assess the morphological variability of species, despite their potential use to study size changes in brittle stars. To confirm the latter, size changes of Ophiocomella alexandri were studied here using this approach. The studied size series of O. alexandri included specimens from 1.64 to 23.64 mm disc diameter (DD). Quantitative and qualitative external morphological characters were examined on each specimen, and quantitative analyses (cluster, one-way permutational analysis of variance, and discriminant analysis) were employed to identify size groups within the species. The allometric relationship disc diameter-total arm length (DD-AL) was estimated for each size group and the combined size groups. Two size groups were identified: Group 1, subdivided into Subgroup 1.1 and Subgroup 1.2, and Group 2. Each size group presented particular characters which were described, discussed, and compared with relevant literature. The relationship DD-AL was positively allometric for Group 1 and combined size groups, and isometric for Group 2. The results highlight the potential of quantitative analyses to address size-related morphological changes in ophiuroids, and the importance of conducting this type of study to correctly identify species regardless of their size. This is the first study to describe size-related morphological changes of a brittle star from the Eastern Pacific, and the first one focused on a member of Ophiocomidae globally.

Celastrol and Melatonin Modify SIRT1, SIRT6 and SIRT7 Gene Expression and Improve the Response of Human Granulosa-Lutein Cells to Oxidative Stress.

An excess of oxidative stress (OS) may affect several physiological processes fundamental to reproduction. SIRT1, SIRT6 and SIRT7 are involved in protection stress systems caused by OS, and they can be activated by antioxidants such as celastrol or melatonin. In this study, we evaluate SIRT1, SIRT6 and SIRT7 gene expression in cultured human granulosa-lutein (hGL) cells in response to OS inductors (glucose or peroxynitrite) and/or antioxidants. Our results show that celastrol and melatonin improve cell survival in the presence and absence of OS inductors. In addition, melatonin induced SIRT1, SIRT6 and SIRT7 gene expression while celastrol only induced SIRT7 gene expression. This response was not altered by the addition of OS inductors. Our previous data for cultured hGL cells showed a dual role of celastrol as a free radical scavenger and as a protective agent by regulating gene expression. This study shows a direct effect of celastrol on SIRT7 gene expression. Melatonin may protect from OS in a receptor-mediated manner rather than as a scavenger. In conclusion, our results show increased hGL cells survival with melatonin or celastrol treatment under OS conditions, probably through the regulation of nuclear sirtuins' gene expression.

El estudio de receptividad endometrial ER®map mejora los resultados reproductivos tras fallos previos de implantación en ciclos de fecundación in vitro / ER®map endometrial receptivity study improves reproductive outcomes after previous implantation failure in in vitro fertilisation cycles

Introducción: Los fallos repetidos en fecundación in vitro constituyen un reto en los tratamientos de fertilidad, sobre todo en ciclos con embriones de buena calidad, donde el endometrio parece ser la causa del fracaso reproductivo. Las pruebas diagnósticas dirigidas para la evaluación del endometrio óptimo, antes de una nueva transferencia, siguen siendo un reto para los tratamientos de reproducción asistida. El test de receptividad endometrial Endometrial Receptivity Map (ER®map) (Pronacera Therapeutics SL, Sevilla, España) nos aporta nueva información endometrial para personalizar la transferencia embrionaria siguiente, pudiendo mejorar así los resultados reproductivos de las pacientes con fallos previos de implantación. Objetivo: El objetivo principal es conocer si existen diferencias en la tasa de embarazo evolutivo (OPR) y tasa de embarazo clínico (PR) tras transferencias embrionarias fallidas previas con embriones de buena calidad, entre el grupo de estudio (E) con biopsia endometrial para estudio de receptividad endometrial previa a una nueva transferencia, y el grupo de control (C) con nueva transferencia estándar sin estudio anterior de receptividad endometrial. Material y métodos: Estudio observacional, analítico, longitudinal, retrospectivo de casos y controles históricos, realizado en la Unidad de Reproducción Asistida (URA) del Hospital Quirónsalud Barcelona, incluyendo a 104 pacientes con una o más transferencias embrionarias previas fallidas de embriones de buena calidad entre los años 2017 a 2019. A las pacientes con dos o más transferencias fallidas previas se les realizó una histeroscopia diagnóstica, junto a una analítica con la determinación de anticoagulante lúpico, anticuerpos antiB2 glicoproteina IgG/IgM, anticuerpos anticardiolipina IgG/IgM, y trombofilia hereditaria como parte del estudio de fallos de implantación del centro...(AU)

Introduction: Repeated failures in in vitro fertilization are a challenge in fertility treatments, especially in cycles with good quality embryos, where the endometrium appears to be the cause of reproductive failure. Targeted diagnostic tests for evaluation of the optimal endometrium before a new transfer remains a challenge for assisted reproduction treatments. The Endometrial Receptivity Map (ER®map Pronacera Therapeutics SL, Seville, Spain) test provides new endometrial information to customize the next embryo transfer to improve reproductive outcomes for patients with previous implantation failure. Objective: The main objective is to determine whether there are differences in the ongoing pregnancy rate by embryo transfer (OPR), after previous failed embryo transfers with good quality embryos, between the study group (E) with endometrial biopsy for endometrial receptivity study prior to a new transfer, and the control group (C) with new standard transfer without previous endometrial receptivity study. Material and methods: Observational, analytical, longitudinal, retrospective study of cases and historical controls, conducted in the Assisted Reproduction Unit (ARU) of the Hospital Quirónsalud Barcelona, including 104 patients with one or more previous failed embryo transfers with good quality embryos between the periods 2017-2019. Patients with more than one previous failed transfer underwent a diagnostic hysteroscopy, and an analysis was requested with the determination of: lupus anticoagulant, anti-B2-glycoprotein IgG/IgM antibodies, anti-cardiolipin IgG/IgM antibodies, and hereditary thrombophilia as part of the study of implantation failures in the centre.(AU)

The Crystal Structure of Cysteamine Dioxygenase Reveals the Origin of the Large Substrate Scope of This Vital Mammalian Enzyme.

We report the crystal structure of the mammalian non-heme iron enzyme cysteamine dioxygenase (ADO) at 1.9 Šresolution, which shows an Fe and three-histidine (3-His) active site situated at the end of a wide substrate access channel. The open approach to the active site is consistent with the recent discovery that ADO catalyzes not only the conversion of cysteamine to hypotaurine but also the oxidation of N-terminal cysteine (Nt-Cys) peptides to their corresponding sulfinic acids as part of the eukaryotic N-degron pathway. Whole-protein models of ADO in complex with either cysteamine or an Nt-Cys peptide, generated using molecular dynamics and quantum mechanics/molecular mechanics calculations, suggest occlusion of access to the active site by peptide substrate binding. This finding highlights the importance of a small tunnel that leads from the opposite face of the enzyme into the active site, providing a path through which co-substrate O2 could access the Fe center. Intriguingly, the entrance to this tunnel is guarded by two Cys residues that may form a disulfide bond to regulate O2 delivery in response to changes in the intracellular redox potential. Notably, the Cys and tyrosine residues shown to be capable of forming a cross-link in human ADO reside ∼7 Šfrom the iron center. As such, cross-link formation may not be structurally or functionally significant in ADO.