Notes

Very high alpha-fetoprotein-producing adrenal hepatoid adenocarcinoma.
Cholestatic-liver diseases (CLDs) arise from diverse causes ranging from genetic factors to drug-induced cholestasis. The so-called diseases of civilization (obesity, diabetes, metabolic disorders, non-alcoholic liver disease, cardiovascular diseases, etc.) are intricately implicated in liver and gall bladder diseases. Although CLDs have been extensively studied, there seem to be important gaps in the understanding of human disease. Despite the fact that many animal models exist and substantial clinical data are available, translation of this knowledge towards therapy has been disappointingly limited. Recent advances in liver cell culture such as in vivo-like 3D cultivation of human primary hepatic cells, human induced pluripotent stem cell-derived hepatocytes; and cutting-edge analytical techniques such as 'omics' technologies and high-content screenings could play a decisive role in deeper mechanistic understanding of CLDs. This Topical Review proposes a roadmap to human biology-based research using omics technologies providing quantitative information on mechanisms in an adverse outcome/disease pathway framework. With modern sensitive tools, a shift in paradigm in human disease research seems timely and even inevitable to overcome species barriers in translation.Atmospheric vapour pressure deficit (VPD) is the driving force for plant transpiration. Plants have different strategies to respond to this 'atmospheric drought'. Deposited aerosols on leaf surfaces can interact with plant water relations and may influence VPD response. We studied transpiration and water use efficiency of pine, beech and sunflower by measuring sap flow, gas exchange and carbon isotopes, thereby addressing different time scales of plant/atmosphere interaction. Plants were grown (i) outdoors under rainfall exclusion (OD) and in ventilated greenhouses with (ii) ambient air (AA) or (iii) filtered air (FA), the latter containing less then 1% ambient aerosol concentrations. In addition, some AA plants were sprayed once with 25 mM salt solution of (NH4 )2 SO4 or NaNO3 . Carbon isotope values (δ(13) C) became more negative in the presence of more particles; more negative for AA compared to FA sunflower and more negative for OD Scots pine compared to other growth environments. FA beech had less negat pollution and climate change. Wicks cause a deviation from the analogy between CO2 and water pathways through stomata, bringing some principal assumptions of gas exchange theory into question.Initial risk assessment to estimate 10-year risk of cardiovascular disease (CVD) is completed by Framingham Risk Score (FRS). In 2012 2 modifications were added to FRS by the Canadian Cardiovascular Society FRS is doubled in subjects aged 30-59 years who have CVD present in a first-degree relative before 55 years of age for men and 65 years of age for women; and cardiovascular age is calculated for each individual. Our aim was to implement these modifications and evaluate differences compared with traditional FRS. Further, we evaluated the association between dietary intake and 10-year risk. The Canadian Health Measures Survey data cycle 1 was used among participants aged 30-74 years (n = 2730). Descriptive and logistic regression analyses were conducted using STATA SE 11. Fluorouracil Using modified FRS for predicting 10-year risk of CVD significantly increased the estimated risk compared with the traditional approach, 8.66% ± 0.35% versus 6.06% ± 0.18%, respectively. Greater impact was observed with the "cardiovascular age" modification in men versus women. The distribution of Canadians in low- ( less then 10%) and high-risk (≥20%) categories of CVD show a significant difference between modified and traditional FRS 67.4% versus 79.6% (low risk) and 13.7% versus 4.5% (high risk), respectively. The odds of having risk ≥10% was significantly greater in low-educated, abdominally obese individuals or those with lower consumption of breakfast cereal and fruit and vegetable and greater potato and potato products consumption. In conclusion, the traditional FRS method significantly underestimates CVD risk in Canadians; thus, applying modified FRS is beneficial for screening. Additionally, fibre consumption from fruit and vegetable or breakfast cereals might be beneficial in reducing CVD risks.The aims of this cross-sectional study were to explore the ability of serum interleukin 18 (IL-18) and adiponectin to identify metabolic syndrome (MetS), and to verify their association with an index of central lipid overaccumulation (lipid accumulation product (LAP)) and cardiometabolic risk factors in a population of middle-aged Brazilian men. A group of 218 apparently healthy middle-aged Brazilian men (age, 50.3 ± 4.97 years) underwent anthropometric, clinical, sociodemographic, and standard serum biochemical assessments. LAP was calculated and the study participants were categorized into 3 groups according to serum IL-18 and adiponectin cut-points tertiles to verify the association of these biomarkers with cardiometabolic risk factors. The MetS group had more less active (p = 0.03) and obese (p less then 0.01) individuals who exhibited higher IL-18 (p less then 0.01) and lower adiponectin (p less then 0.01) than did those in the group with no MetS. After adjustments (age, smoking, alcohol consumption, physical activity level, and total body fat), serum IL-18 ≥ 336.4 pg/mL was an independent factor for MetS occurrence and it was directly associated with LAP (≥51.28), central obesity, hypertriglyceridemia, and hypertension (p less then 0.05), but not with high-density lipoprotein cholesterol (HDL-C). Serum adiponectin ≥ 7.02 μg/mL was negatively associated with MetS occurrence, LAP, hypertriglyceridemia, and low HDL-C (p less then 0.05), but not with central obesity and hypertension. In conclusion, both IL-18 and adiponectin demonstrated the ability to identify MetS in this population, with IL-18 being more accurate. The association of these biomamarkers with LAP and cardiometabolic risk factors highlights its relevance as a diagnostic tool.A general synthetic strategy to cis-fused bicyclic γ-butyrolactones via the retro-Diels-Alder reaction/intramolecular conjugate ene cascade (RDA/ICE) reaction under the flash-vacuum pyrolysis of maleic anhydride adducts is developed. The reaction gave high yields of products with high stereoselectivity. The existence of the difluoromethyl or trifluoromethyl group at the γ-position of the in situ-generated homoalkenyl- or homoalkynyl-α,β-unsaturated γ-butyrolactones was found to accelerate the rate of the intramolecular conjugate ene reaction leading to γ-difluoromethylated and γ-trifluoromethylated cis-fused bicyclic γ-butyrolactones.
Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) has been shown to increase in parallel with platelet activation in acute ischaemic and thrombotic diseases. There has been no study evaluating SCUBE1 levels in patients with overt hyperthyroidism (OHyper) and subclinical hyperthyroidism (SHyper), conditions which are known to show impairment of both endothelial and platelet function. This study sought to evaluate SCUBE1 concentrations in patients with SHyper and OHyper, and assessed the effects of antithyroid drug (ATD) therapy on circulating SCUBE1 levels.

Forty-five untreated patients with OHyper, 20 untreated patients with SHyper and 30 age- and sex-matched healthy controls were prospectively included in the study. Biochemical and hormonal parameters were evaluated in all patients before and after treatment.

Compared with the control subjects, SCUBE1 levels were significantly increased in patients with SHyper and OHyper (P < 0·0001 and P = 0·002, respectively). SCUBE1 levels were not significantly different in patients with OHyper compared with patients with SHyper. There was no significant correlation between serum thyroid hormones and SCUBE1 levels. Plasma SCUBE1 levels decreased significantly in both OHyper and SHyper after ATD treatment (P < 0·05).

Increased SCUBE1 levels in both SHyper and OHyper patients may reflect increased platelet activation and possible endothelial dysfunction, which might augment the risk for atherosclerotic and atherothrombotic complications. SCUBE1 may be used as a reliable marker of endothelial damage in hyperthyroidism, especially in the subclinical period.
Increased SCUBE1 levels in both SHyper and OHyper patients may reflect increased platelet activation and possible endothelial dysfunction, which might augment the risk for atherosclerotic and atherothrombotic complications. SCUBE1 may be used as a reliable marker of endothelial damage in hyperthyroidism, especially in the subclinical period.The natriuretic peptides (NPs), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), have vasoactive functions that concern humans and most animals, but their specific effects on cerebral circulation are poorly understood. We therefore examined the responsiveness of cerebral arteries to different doses of the natriuretic peptides in animals and humans. We conducted a dose-response experiment in guinea pigs (in vitro) and a double-blind, three-way cross-over study in healthy volunteers (in vivo). In the animal experiment, we administered cumulative doses of NPs to pre-contracted segments of cerebral arteries. In the main study, six healthy volunteers were randomly allocated to receive two intravenous doses of ANP, BNP or CNP, respectively, over 20 min on three separate study days. We recorded blood flow velocity in the middle cerebral artery (VMCA) by transcranial Doppler. In addition, we measured temporal and radial artery diameters, headache response and plasma concentrations of the NPs. In guinea pigs, ANP and BNP but not CNP showed significant dose-dependent relaxation of cerebral arteries. In healthy humans, NP infusion had no effect on mean VMCA, and we found no difference in hemodynamic responses between the NPs. Furthermore, natriuretic peptides did not affect temporal and radial artery diameters or induce headache. In conclusion, natriuretic peptides in physiological and pharmacological doses do not affect blood flow velocity in the middle cerebral artery or dilate extracerebral arteries in healthy volunteers.There are a number of cognitive models of autism that aim to explain how mental processes are handled differently in the condition. These models make claims about the nature of cognitive function in people with autism, and suggest that these differences applied in social contexts lead to the characteristic behavioural patterns. However, it is difficult to study these cognitive differences directly because of the complexity of social situations. Studies of perceptual function are tempting as an alternative way to study cognition because it is far easier to control the conditions and the stimuli that participants are exposed to. This makes hypothesis generation and interpretation of results more objective and more convincing. However, the study of perception in autism hasn't been very productive in contributing towards a model of cognition in autism. In many areas there are studies reporting contradictory results, preventing arrival at a consensus about the largest unresolved issues in the area. These studies tend to be repeated multiple times, but continue to provide contradictory evidence that doesn't allow us to place confidence in any of the cognitive models.
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