Pediatric Cushing disease: disparities in disease severity and outcomes in the Hispanic and African-American populations.

BackgroundLittle is known about the contribution of racial and socioeconomic disparities to severity and outcomes in children with Cushing disease (CD).MethodsA total of 129 children with CD, 45 Hispanic/Latino or African-American (HI/AA) and 84 non-Hispanic White (non-HW), were included in this study. A 10-point index for rating severity (CD severity) incorporated the degree of hypercortisolemia, glucose tolerance, hypertension, anthropomorphic measurements, disease duration, and tumor characteristics. Race, ethnicity, age, gender, local obesity prevalence, estimated median income, and access to care were assessed in regression analyses of CD severity.ResultsThe mean CD severity in the HI/AA group was worse than that in the non-HW group (4.9±2.0 vs. 4.1±1.9, P=0.023); driving factors included higher cortisol levels and larger tumor size. Multiple regression models confirmed that race (P=0.027) and older age (P=0.014) were the most important predictors of worse CD severity. When followed up a median of 2.3 years after surgery, the relative risk for persistent CD combined with recurrence was 2.8 times higher in the HI/AA group compared with that in the non-HW group (95% confidence interval: 1.2-6.5).ConclusionOur data show that the driving forces for the discrepancy in severity of CD are older age and race/ethnicity. Importantly, the risk for persistent and recurrent CD was higher in minority children

A novel organic-rich meteoritic clast from the outer solar system

The Zag meteorite which is a thermally-metamorphosed H ordinary chondrite contains a primitive xenolitic clast that was accreted to the parent asteroid after metamorphism. The cm-sized clast contains abundant large organic grains or aggregates up to 20μm in phyllosilicate-rich matrix. Here we report organic and isotope analyses of a large (~10μm) OM aggregate in the Zag clast. The X-ray micro-spectroscopic technique revealed that the OM aggregate has sp2 dominated hydrocarbon networks with a lower abundance of heteroatoms than in IOM from primitive (CI,CM,CR) carbonaceous chondrites, and thus it is distinguished from most of the OM in carbonaceous meteorites. The OM aggregate has high D/H and 15N/14N ratios (δD=2,370±74‰ and δ15N=696±100‰), suggesting that it originated in a very cold environment such as the interstellar medium or outer region of the solar nebula, while the OM is embedded in carbonate-bearing matrix resulting from aqueous activities. Thus, the high D/H ratio must have been preserved during the extensive late-stage aqueous processing. It indicates that both the OM precursors and the water had high D/H ratios. Combined with 16O-poor nature of the clast, the OM aggregate and the clast are unique among known chondrite groups. We further propose that the clast possibly originated from D/P type asteroids or trans-Neptunian Objects

Serum estradiol/progesterone ratio on day of embryo transfer may predict reproductive outcome following controlled ovarian hyperstimulation and in vitro fertilization

BACKGROUND: To determine whether estradiol-to-progesterone (E(2)/P) ratios at the time of embryo transfer (ET) have an effect on implantation and pregnancy in IVF cycles. METHODS: 239 women consecutively treated by IVF or ICSI were retrospectively analyzed and early luteal serum E(2 )and P were measured on the day of ET. Transfer occurred after a variable in vitro culture period ranging from 4–7 days after ovulation induction (OI). Following ET, serum E(2)/P ratios were calculated for clinical pregnancies, preclinical abortions and non-coneption cycles. RESULTS: Receiver-operator curve analysis demonstrated that the E(2)/P ratio could differentiate between clinical pregnancies and non-pregnant cycles (area under the curve on OI +4 days = 0.70; 95% CI = 0.60–0.80; p = 0.003, on OI +5 days = 0.76; 95% CI = 0.64–0.88; p = 0.001, OI +7 days = 0.85; 95% CI = 0.75–0.96; p < 0.0001). CONCLUSION: These retrospective data may hold prognostic value regarding endometrial receptivity as reflected by E(2)/P measurements and may help improve IVF treatment outcome. Further prospective studies should be undertaken to confirm these obersveration

Effect of a 14-day course of systemic corticosteroids on the hypothalamic-pituitary-adrenal-axis in patients with acute exacerbation of chronic obstructive pulmonary disease

<p/> <p>Background</p> <p>As supra-physiological intake of corticosteroids is a well known risk factor for the development of adrenal insufficiency, we investigated the function of the hypothalamic-pituitary-adrenal (HPA) axis during a 14-day course of systemic corticosteroids in patients with acute exacerbation of chronic obstructive pulmonary disease using clinical and laboratory measures.</p> <p>Methods</p> <p>A systematic clinical and laboratory assessment including measurement of basal cortisol levels and the response to low dose (1 μg) ACTH stimulation was performed in nine patients before, on the first and the last day of treatment, as well as 2, 7 and 21 days after corticosteroid withdrawal.</p> <p>Results</p> <p>At baseline, all nine patients had normal responses to 1 μg ACTH. On the first day of steroid treatment, 78% had a blunted peak cortisol response. This percentage increased to 89% after 14 days of steroid treatment. 78%, 33% and 33% of the patients had a blunted cortisol response to ACTH 2, 7, and 21 days after corticosteroid withdrawal, respectively. ROC curve analysis revealed that only basal cortisol concentrations (AUC 0.89), but not ACTH concentrations (AUC 0.49) or clinical signs (AUC 0.47) were predictive of an impaired function of the HPA axis. Basal cortisol levels of > 400 and < 150 nmol/l were 96% and 100% sensitive for a normal or pathological response to the ACTH stimulation test, respectively.</p> <p>Conclusion</p> <p>Immediate and prolonged suppression of the HPA axis is a common finding in otherwise asymptomatic patients undergoing systemic steroid treatment for acute exacerbation of chronic obstructive pulmonary disease and can reliably be assessed with the low-dose ACTH test.</p

Pulmonary arterial hypertension: an update

Pulmonary arterial hypertension (PAH), defined as group 1 of the World Heart Organisation (WHO) classification of pulmonary hypertension, is an uncommon disorder of the pulmonary vascular system. It is characterised by an increased pulmonary artery pressure, increased pulmonary vascular resistance and specific histological changes. It is a progressive disease finally resulting in right heart failure and premature death. Typical symptoms are dyspnoea at exercise, chest pain and syncope; furthermore clinical signs of right heart failure develop with disease progression. Echocardiography is the key investigation when pulmonary hypertension is suspected, but a reliable diagnosis of PAH and associated conditions requires an intense work-up including invasive measurement by right heart catheterisation. Treatment includes general measures and drugs targeting the pulmonary artery tone and vascular remodelling. This advanced medical therapy has significantly improved morbidity and mortality in patients with PAH in the last decade. Combinations of these drugs are indicated when treatment goals of disease stabilisation are not met. In patients refractory to medical therapy lung transplantation should be considered an option

Linear dichroism and circular dichroism in photosynthesis research

The efficiency of photosynthetic light energy conversion depends largely on the molecular architecture of the photosynthetic membranes. Linear- and circular-dichroism (LD and CD) studies have contributed significantly to our knowledge of the molecular organization of pigment systems at different levels of complexity, in pigment–protein complexes, supercomplexes, and their macroassemblies, as well as in entire membranes and membrane systems. Many examples show that LD and CD data are in good agreement with structural data; hence, these spectroscopic tools serve as the basis for linking the structure of photosynthetic pigment–protein complexes to steady-state and time-resolved spectroscopy. They are also indispensable for identifying conformations and interactions in native environments, and for monitoring reorganizations during photosynthetic functions, and are important in characterizing reconstituted and artificially constructed systems. This educational review explains, in simple terms, the basic physical principles, and theory and practice of LD and CD spectroscopies and of some related quantities in the areas of differential polarization spectroscopy and microscopy

Contact metamorphism associated to the Penamacor - Monsanto granitic intrusion (Central Portugal): geochemical, isotopic and mineralogical features

Contact metamorphism related to Variscan and late-Variscan granitic plutons in the Iberian Peninsula is superimposed on medium-grade regional metamorphism, making it often difficult to evaluate per se the thermal effects due to those intrusions and explaining the paucity of scientific literature on the subject. An exhaustive set of geochemical, isotopic and mineralogical data on the contact-zone metasediments hosting the Penamacor-Monsanto granite (Central Iberian Zone, Portugal) provides a significant contribution to the characterization of low- to intermediate-grade contact metamorphism in geological contexts formerly affected by regional metamorphism. The metasediments hosting the Penamacor-Monsanto pluton belong to the extensive detrital sequence of the ante-Ordovician Schist-Greywacke Complex. Bulk geochemistry, oxygen isotope data and crystal-chemistry of key minerals from those contact-zone and neighbouring metasediments have made it possible to infer metamorphic conditions on the contact zone of this granitic intrusion, and to distinguish them from late boron-metasomatism at the exocontact. Mineral paragenesis (muscovite + biotite + chlorite quartz plagioclase cordierite, in spotted-schists; biotite + chlorite quartz plagioclase ( cordierite), in hornfelses) and the composition of these coexisting mineral phases indicate that most of the contact rocks reached the biotite zone (or even the cordierite zone, in some cases), equivalent to upper greenschist – lower amphibolite metamorphic grade. The relatively narrow range of O-isotope temperatures estimated for the crystallization of the marginal granites (550-625ºC) explains the absence of significant effects of thermal flow anisotropy on the contact-zone rocks. Besides, textural, paragenetic, mineralogical, isotopic and geochemical nuances observed in hornfelses and spotted-schists seem mainly related to the local host-rock heterogeneities, rather than to thermal effects. The relatively low temperatures estimated for granitoid emplacement and their restricted isotopic and mineralogical impacts on the metasedimentary host-rocks account for the narrow metamorphic aureole associated with the Penamacor-Monsanto pluton, and suggest this massif may correspond to the outcropping tip of a larger granitic intrusion at depth.Las intrusions graníticas Varíscicas y tardivaríscicas de la Península Ibérica dieron lugar a un metamorfsmo de contacto que afecta a un encajante previamente sometido a un metamorfsmo regional de grado medio, lo que difculta separar los efectos térmicos de aquellos regionales, y explica la escasez de estudios sobre el mismo. El estudio detallado de la zona de contacto entre el Granito de Penamacor-Monsanto (Zona Centro-Ibérica; Portugal) y su encajante metasedimentario mediante técnicas geoquímicas, mineralógicas e isotópicas supone una notable contribución al conocimiento y caracterización del metamorfsmo de contacto de grados bajos a intermedios en contextos geológicos previamente afectados por metamorfsmo regional. El encajante metasedimentario del Plutón de Penamacor-Monsanto es parte de la amplia secuencia detrítica ante-Ordovícia conocida como Complejo Esquisto-Grawackico. Datos geoquímicos de roca total y cristaloquímicos de los minerales más característicos, y relaciones isotópicas de oxígeno en la zona de contacto y metasedimentos aledaños permiten inferir las condiciones metamórfcas en la zona de contacto de dicha intrusión, y diferenciarla de aquella afectada por metasomatismo tardío por B. La paragénesis mineral (muscovita + biotita + clorita ± cuarzo ± plagioclasa ± cordierita en los esquistos moteados; biotita + clorita ± cuarzo ± plagiclasa (± cordierita) en corneanas) y la composición de las fases minerales coexistentes indican que la mayoría de rocas del contacto alcanzaron la zona de la biotita (e incluso, en algunos casos, aquella de la cordierita), equivalente a la parte alta del grado metamórfco de los esquistos verdes, o a la parte baja de las anfbolitas. El rango relativamente pequeño de temperaturas de cristalización de los granitos marginales (550-625°C), calculado mediante isótopos de oxígeno, explica la carencia de anisotropías térmicas signifcativas en las rocas del contacto. Las sutiles diferencias texturales, paragenéticas, mineralógicas, isotópicas y geoquímicas en esquistos moteados y corneanas parecen relacionadas con heterogeneidades locales de los encajantes, y no con efectos térmicos diferenciados. Las temperaturas relativamente bajas estimadas durante la intrusión del granito de Penamacor-Monsanto, y el limitado efecto mineralógico e isotópico sobre el encajante metasedimentario, dan lugar a una aureola de contacto estrecha, y sugieren que este macizo puede corresponder al techo de una intrusión mayor en profundidad.Funding was provided by FCT—Fundação para a Ciên cia e Tecnologia, through project METMOB (PTDC/CTE-GIX/116204/2009

Characterising the CI and CI-like carbonaceous chondrites using thermogravimetric analysis and infrared spectroscopy

The CI and CI-like chondrites provide a record of aqueous alteration in the early solar system. However, the CI-like chondrites differ in having also experienced a late stage period of thermal metamorphism. In order to constrain the nature and extent of the aqueous and thermal alteration, we have investigated the bulk mineralogy and abundance of H2O in the CI and CI-like chondrites using thermogravimetric analysis and infrared spectroscopy. The CI chondrites Ivuna and Orgueil show significant mass loss (28.5–31.8 wt.%) upon heating to 1000 °C due to dehydration and dehydroxylation of abundant phyllosilicates and Fe-(oxy)hydroxides and the decomposition of Fe-sulphides, carbonates and organics. Infrared spectra for Ivuna and Orgueil have a prominent 3-μm feature due to bound −OH/H2O in phyllosilicates and Fe-(oxy)hydroxides and only a minor 11-μm feature from anhydrous silicates. These characteristics are consistent with previous studies indicating that the CI chondrites underwent near-complete aqueous alteration. Similarities in the total abundance of H2O and 3 μm/11 μm ratio suggest that there is no difference in the relative degree of hydration experienced by Ivuna and Orgueil. In contrast, the CI-like chondrites Y-82162 and Y-980115 show lower mass loss (13.8–18.8 wt.%) and contain >50 % less H2O than the CI chondrites. The 3-μm feature is almost absent from spectra of Y-82162 and Y-980115 but the 11-μm feature is intense. The CI-like chondrites experienced thermal metamorphism at temperatures >500 °C that initially caused dehydration and dehydroxylation of phyllosilicates before partial recrystallization back into anhydrous silicates. The surfaces of many C-type asteroids were probably heated through impact metamorphism and/or solar radiation, so thermally altered carbonaceous chondrites are likely good analogues for samples that will be returned by the Hayabusa-2 and OSIRIS-REx missions