Glucose enhancement of memory is modulated by trait anxiety in healthy adolescent males

Glucose administration is associated with memory enhancement in healthy young individuals under conditions of divided attention at encoding. While the specific neurocognitive mechanisms underlying this ‘glucose memory facilitation effect’ are currently uncertain, it is thought that individual differences in glucoregulatory efficiency may alter an individual’s sensitivity to the glucose memory facilitation effect. In the present study, we sought to investigate whether basal hypothalamic–pituitary–adrenal axis function (itself a modulator of glucoregulatory efficiency), baseline self-reported stress and trait anxiety influence the glucose memory facilitation effect. Adolescent males (age range = 14–17 years) were administered glucose and placebo prior to completing a verbal episodic memory task on two separate testing days in a counter-balanced, within-subjects design. Glucose ingestion improved verbal episodic memory performance when memory recall was tested (i) within an hour of glucose ingestion and encoding, and (ii) one week subsequent to glucose ingestion and encoding. Basal hypothalamic–pituitary–adrenal axis function did not appear to influence the glucose memory facilitation effect; however, glucose ingestion only improved memory in participants reporting relatively higher trait anxiety. These findings suggest that the glucose memory facilitation effect may be mediated by biological mechanisms associated with trait anxiety

Diurnal Variation of Markers for Cholesterol Synthesis, Cholesterol Absorption, and Bile Acid Synthesis:A Systematic Review and the Bispebjerg Study of Diurnal Variations

Human studies have shown diurnal rhythms of cholesterol and bile acid synthesis, but a better understanding of the role of the circadian system in cholesterol homeostasis is needed for the development of targeted interventions to improve metabolic health. Therefore, we performed a systematic literature search on the diurnal rhythms of cholesterol synthesis and absorption markers and of bile acid synthesis markers. We also examined the diurnal rhythms of the cholesterol synthesis markers lathosterol and desmosterol, and of the cholesterol absorption markers cholestanol, campesterol, and sitosterol in serum samples from the Bispebjerg study. These samples were collected every three hours over a 24-h period in healthy males (n = 24) who consumed low-fat meals. The systematic search identified sixteen papers that had examined the diurnal rhythms of the cholesterol synthesis markers lathosterol (n = 3), mevalonate (n = 9), squalene (n = 2), or the bile acid synthesis marker 7 alpha-hydroxy-4-cholesten-3-one (C4) (n = 4). Results showed that lathosterol, mevalonate, and squalene had a diurnal rhythm with nocturnal peaks, while C4 had a diurnal rhythm with daytime peaks. Furthermore, cosinor analyses of the serum samples showed a significant diurnal rhythm for lathosterol (cosinor p 0.05). In conclusion, cholesterol synthesis and bile acid synthesis have a diurnal rhythm, though no evidence for a diurnal rhythm of cholesterol absorption was found under highly standardised conditions. More work is needed to further explore the influence of external factors on the diurnal rhythms regulating cholesterol homeostasis

Analyse des délais de prise en charge des cancers thoraciques : étude prospective

RésuméIntroductionLe cancer broncho-pulmonaire est la première cause de décès par cancer en France. Son diagnostic est le plus souvent tardif, alors que le délai entre le début des symptômes et la prise en charge est considéré comme un facteur aggravant.Matériel et méthodesNotre étude prospective a recueilli les différentes dates de prise en charge de 139 patients consécutifs bénéficiant d’un traitement primaire pour un cancer thoracique dans notre hôpital entre novembre 2008 et mai 2009. L’objectif de cette étude était d’évaluer différents délais de prise en charge des patients porteurs d’un cancer thoracique quelle que soit sa prise en charge thérapeutique (médicale ou chirurgicale) et de déterminer la cause de ces délais.RésultatsLe délai médian entre la première imagerie pathologique et le traitement est de 9,6 semaines. Les délais étaient significativement plus courts dans les stades tardifs et les carcinomes à petites cellules (p=0,001). Il existait une tendance à des délais plus courts pour les femmes et des délais plus longs pour les classes d’âge les plus élevées.ConclusionL’évaluation des délais de prise en charge, en particulier pour les stades précoces, s’intègre dans le contrôle de la qualité de prise en charge de ces pathologies.SummaryIntroductionLung cancer is the main cause of cancer death in France. The diagnosis is often late and the delay between the onset of symptoms and management is considered an aggravating factor.Material and methodsOur prospective study collected the dates of the start of management of 139 consecutive patients receiving first line treatment for thoracic cancer in our hospital between November 2008 and May 2009. The aim of this study was to evaluate the delays in medical or surgical treatments in patients with thoracic cancer and to determine the cause of these delays.ResultsThe median delay between the first abnormal chest X-ray and treatment was 9.6 weeks. The delays were significantly shorter in the late stages and in small cell cancer (P=0.001). There was a tendency for shorter delays in women and for longer delays in older patients.ConclusionEvaluation of the delays in treatment, particularly in the early stages, is part of the quality control of management of these diseases

Sex-opposed inflammatory effects of 27-hydroxycholesterol are mediated via differences in estrogen signaling

Despite the increased awareness of differences in the inflammatory response between men and women, only limited research has focused on the biological factors underlying these sex differences. The cholesterol derivative 27-hydroxycholesterol (27HC) has been shown to have opposite inflammatory effects in independent experiments using mouse models of atherosclerosis and non-alcoholic steatohepatitis (NASH), pathologies characterized by cholesterol-induced inflammation. As the sex of mice in these in vivo models differed, we hypothesized that 27HC exerts opposite inflammatory effects in males compared to females. To explore whether the sex-opposed inflammatory effects of 27HC translated to humans, plasma 27HC levels were measured and correlated with hepatic inflammatory parameters in obese individuals. To investigate whether 27HC exerts sex-opposed effects on inflammation, we injected 27HC into female and male Niemann–Pick disease type C1 mice (Npc1nih) that were used as an extreme model of cholesterol-induced inflammation. Finally, the involvement of estrogen signaling in this mechanism was studied in bone marrow-derived macrophages (BMDMs) that were treated with 27HC and 17β-estradiol (E2). Plasma 27HC levels showed opposite correlations with hepatic inflammatory indicators between female and male obese individuals. Likewise, hepatic 27HC levels oppositely correlated between female and male Npc1nih mice. Twenty-seven hydroxycholesterol injections reduced hepatic inflammation in female Npc1nih mice in contrast to male Npc1nih mice, which showed increased hepatic inflammation after 27HC injections. Furthermore, 27HC administration also oppositely affected inflammation in female and male BMDMs cultured in E2-enriched medium. Remarkably, female BMDMs showed higher ERα expression compared to male BMDMs. Our findings identify that the sex-opposed inflammatory effects of 27HC are E2-dependent and are potentially related to differences in ERα expression between females and males. Hence, the individual’s sex needs to be taken into account when 27HC is employed as a therapeutic tool as well as in macrophage estrogen research in general

Evolución de diversas actividades enzimáticas durante la maduración del chirimoyo n atmosfera controlada

Cherimoya fruits after harvesting have a short shelf life thus conditioning their marketing. Polyphenoloxidase, peroxidase, catalase and acid phosphatase are enzymes implicated in the ripening process of cherimoya. We have studied the variations of activity for these enzymes during cherimoya ripening in an C02 atmosphere and in the same atmosphere in presence sulphite. There was a marked decrease in the protein contents of both epicarp and mesocarp, during fruit ripening in C02 atmosphere. Enzymic activities also decreased at the beginning of the ripening. These low activities were maintained while fruits were in presence of C02 or C02 and sulphite.El fruto del chirimoyo tiene un proceso de maduración muy corto, lo cual afecta a su vida comercial. En este proceso están implicadas una serie de enzimas, como son polifenoloxidasa, peroxidasa, catalasa y fosfatasa ácida. Se han estudiado la evolución de las actividades de estas enzimas, almacenando los frutos en atmósfera de C02 y en presencia de sulfito. Los resultados obtenidos indican que existe una disminución en la concentración de proteínas totales, tanto en el epicarpio como en el mesocarpio de los frutos, durante la maduración en presencia de C02. Igualmente se produce una disminución de las actividades enzimáticas con este tratamiento. Esta baja actividad se mantiene, al menos durante tres semanas de almacenamiento. La presencia de sulfito en atmósfera de C02, no condiciona variaciones ni en la concentración de proteínas del fruto ni en las actividades enzimáticas

Optical and mid-infrared line emission in nearby Seyfert galaxies

Line ratio diagnostics provide valuable clues on the source of ionizing radiation in galaxies with intense black hole accretion and starbursting events, such as local Seyfert or galaxies at the peak of the star formation history. We aim to provide a reference joint optical and mid-IR analysis for studying AGN identification via line ratios and testing predictions from photoionization models. We obtained homogenous optical spectra with the Southern Africa Large Telescope for 42 Seyfert galaxies with Spitzer/IRS spectroscopy and X-ray to mid-IR multiband data available. After confirming the power of the main optical ([OIII]) and mid-IR ([NeV], [OIV], [NeIII]) emission lines in tracing AGN activity, we explore diagrams based on ratios of optical and mid-IR lines by exploiting photoionization models of different ionizing sources (AGN, star formation and shocks). We find that pure AGN photoionization models are good at reproducing observations of Seyfert galaxies with an AGN fractional contribution to the mid-IR (5-40 micron) emission larger than 50 per cent. For targets with a lower AGN contribution these same models do not fully reproduce the observed mid-IR line ratios. Mid-IR ratios like [NeV]/[NeII], [OIV]/[NeII] and [NeIII]/[NeII] show a dependence on the AGN fractional contribution to the mid-IR unlike optical line ratios. An additional source of ionization, either from star formation or radiative shocks, can help explain the observations in the mid-IR. Among combinations of optical and mid-IR diagnostics in line ratio diagrams, only those involving the [OI]/Halpha ratio are promising diagnostics for simultaneously unraveling the relative role of AGN, star formation and, shocks. A proper identification of the dominant ionizing source would require the exploitation of analysis tools based on advanced statistical techniques as well as spatially resolved data.Comment: 31 pages, 15 figures, 2 tables. Accepted for publication in A&

Systematic review and meta-analysis of the metabolic effects of modified-release hydrocortisone versus standard glucocorticoid replacement therapy in adults with adrenal insufficiency

Context Published studies exploring the metabolic effects of Modified‐Release Hydrocortisone (MR‐HC) replacement in patients with adrenal insufficiency (AI). Objective To compare metabolic effects of MR‐HC with Standard Glucocorticoid (SG) replacement in adults with AI. Randomised control trials (RCTs) were meta‐analysed; non‐RCT studies described narratively with critical appraisal. Data sources PubMed/Medline, EMBASE, CINAHL and CENTRAL were searched to identify relevant articles, published before Aug 2019. Study selection All study types that reported metabolic profile (including anthropometric, glucose and lipid‐related parameters), on patients switched from SG to MR‐HC replacement. Following independent screening from two reviewers, 390 studies were identified, of which 9 studies were included for review (RCT, n=2; non‐RCT, n=7). Data extraction Two independent reviewers assessed each paper for bias and data extraction. Results Meta‐analysis from RCTs (n=2), 104 patients were switched from SG to MR‐HC replacement. Combining treatment effects, at 3‐months post‐therapy switch there was significant reduction in body weight (‐0.82kg; 95% CI: ‐1.24kg to ‐0.40kg; p<0.001) and HbA1c (‐0.13%; 95% CI: ‐0.214% to ‐0.045%; p=0.003). In the sub‐group with Diabetes Mellitus (DM), reduction in HbA1C was more pronounced (‐0.52%; 95% CI: ‐0.82% to ‐0.23%; p<0.001). Non‐RCT studies showed improved anthropometric measures and glucose metabolism up to 48‐months following switch from SG to MR‐HC replacement. Conclusions In adults with AI, replacement with MR‐HC associates with significant improvements in anthropometric measurements and HbA1c compared with SG replacement, particularly those with DM

A transcriptionally distinct CXCL13+CD103+CD8+ T-cell population is associated with B-cell recruitment and neoantigen load in human cancer

The chemokine CXCL13 mediates recruitment of B cells to tumors and is essential for the formation of tertiary lymphoid structures (TLSs). TLSs are thought to support antitumor immunity and are associated with improved prognosis. However, it remains unknown whether TLSs are formed in response to the general inflammatory character of the tumor microenvironment, or rather, are induced by (neo)antigen-specific adaptive immunity. We here report on the finding that the transforming growth factor beta (TGFβ)-dependent CD103+CD8+ tumor-infiltrating T-cell (TIL) subpopulation expressed and produced CXCL13. Accordingly, CD8+ T cells from peripheral blood activated in the presence of TGFβ upregulated CD103 and secreted CXCL13. Conversely, inhibition of TGFβ receptor signaling abrogated CXCL13 production. CXCL13+CD103+CD8+ TILs correlated with B-cell recruitment, TLSs, and neoantigen burden in six cohorts of human tumors. Altogether, our findings indicated that TGFβ plays a non-canonical role in coordinating immune responses against human tumors and suggest a potential role for CXCL13+CD103+CD8+ TILs in mediating B-cell recruitment and TLS formation in human tumors