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Severe factor VIII ( FVIII)-deficient patients with and without FVIII inhibitors cannot be distinguished using FVIII levels. The FVIII assay is sensitive to detect factor levels below 1%. While severe FVIII-deficient, non-inhibitor patients have FVIII < 1%, they may retain unmeasurable residual factor activity. In contrast, inhibitor patients have a FVIII antibody that presumably fully eliminates FVIII activity. It is unknown whether thromboelastography ( TEG) and thrombin generation assay ( TGA) can differentiate between patients with FVIII < 1% with and without the presence of FVIII inhibitors. The primary objective was to discern whether TEG and TGA could differentiate between severe FVIII-deficient patients with and without the presence of FVIII inhibitors. A secondary objective was to correlate TEG and TGA to annualized bleeding rates. This observational study performed TEG and TGA in healthy volunteers ( N = 15), severe FVIII-deficient ( N = 15) and severe FVIII-deficient patients with inhibitors ( N = 15). Kaolin-activated TEG was better at differentiating reaction time (31.3 vs. 120 min respectively, P = 0.004) and kinetics time (6.1 vs. 23.1 min respectively, P = 0.028) between the non-inhibitor and inhibitor patients. TEG activated by tissue factor in plasma-containing corn trypsin inhibitor failed to differentiate groups. The TGA failed to differentiate peak thrombin, endogenous thrombin potential and lag time between groups. There was no correlation between TEG and TGA with annualized bleeding rates. Kaolin-activated TEG, but not TGA, differentiated between severe FVIII-deficient patients with and without inhibitors. These assays did not find a correlation to annualized bleeding rate. [ABSTRACT FROM AUTHOR]

The peritoneal mesothelium exhibits a high regenerative ability. Peritoneal regeneration is concomitant with the appearance, in the coelomic cavity, of a free-floating population of cells whose origin and functions are still under discussion. We have isolated and characterized this cell population and we have studied the process of mesothelial regeneration through flow cytometry and confocal microscopy in a murine model lethally irradiated and reconstituted with GFP-expressing bone marrow cells. In unoperated control mice, most free cells positive for mesothelin, a mesothelial marker, are green fluorescent protein (GFP). However, 24 hrs after peritoneal damage, free mesothelin/ GFP cells appear in peritoneal lavages. Cultured lavage peritoneal cells show colocalization of GFP with mesothelial (mesothelin, cytokeratin) and fibroblastic markers. Immunohistochemical staining of the peritoneal wall also revealed colocalization of GFP with mesothelial markers and with procollagen-1 and smooth muscle α-actin. This was observed in the injured area as well as in the surrounding not-injured peritoneal surfaces. These cells, which we herein call peritoneal repairing cells (PRC), are very abundant 1 week after surgery covering both the damaged peritoneal wall and the surrounding uninjured area. However, they become very scarce 1 month later, when the mesothelium has completely healed. We suggest that PRC constitute a type of monocyte-derived cells, closely related with the tissue-repairing cells known as 'fibrocytes' and specifically involved in peritoneal reparation. Thus, our results constitute a synthesis of the different scenarios hitherto proposed about peritoneal regeneration, particularly recruitment of circulating progenitor cells and adhesion of free-floating coelomic cells. [ABSTRACT FROM AUTHOR]

When integrated weed management approaches are used, visual estimations of weed cover are commonly employed to quantify weed infestation levels in crops. This study assessed the reliability of visual estimation of weed cover, considering various factors which may influence the accuracy and consistency of human perception. Measurements were based on visual estimates of digital images acquired in maize fields. A total of 750 images were assessed independently by four experienced observers using three cover-abundance scales, varying the assessment date or the order in which the images were assessed. A good relationship was generally found between the visual estimates of weed cover and some objective parameters (actual weed cover, weed biomass). The analyses of reliability and repeatability showed no significant differences between the estimations performed by four different observers or by the same observer at different times, independently of the scale used. Nevertheless, the comparison between visual estimations performed by the observers and actual weed cover showed that observers tended to overestimate weed cover at low weed densities and underestimate it when densities were high. Although visual assessments of weed cover were relatively accurate to quantify weed infestation level, our results showed that human perception was not reliable enough to determine actual weed cover close to the class boundaries, both in the lower range (e.g. 5%, 10%) and in the middle range (e.g. 50%) of the scale. This may be a serious limitation for the use of visual methods in threshold-based weed management programmes. [ABSTRACT FROM AUTHOR]

The epicardium has recently been identified as an active and essential element of cardiac development. Recent reports have unveiled a variety of functions performed by the embryonic epicardium, as well as the cellular and molecular mechanisms regulating them. However, despite its developmental importance, a number of unsolved issues related to embryonic epicardial biology persist. In this review, we will summarize our current knowledge about ( i) the ontogeny and evolution of the epicardium, including a discussion on the evolutionary origins of the proepicardium (the epicardial primordium), ( ii) the nature of epicardial-myocardial interactions during development, known to be essential for myocardial growth and maturation, and ( iii) the contribution of epicardially derived cells to the vascular and connective tissue of the heart. We will finish with a note on the relationships existing between the primordia of the viscera and their coelomic epithelial lining. We would like to suggest that at least a part of the properties of the embryonic epicardium are shared by many other coelomic cell types, such that the role of epicardium in cardiac development is a particular example of a more general mechanism for the contribution of coelomic and coelomic-derived cells to the morphogenesis of organs such as the liver, kidneys, gonads or spleen. [ABSTRACT FROM AUTHOR]

We searched the Spanish and Portuguese pharmacovigilance databases for spontaneous case reports of heart rhythm disturbances associated with rupatadine and other new H1 antihistamines. Five cases were found involving patients treated with rupatadine (13.9% of all reports relating to this drug). In all five cases, the reaction started after exposure and resolved when the drug was discontinued. In two cases, rupatadine was the only medication being taken by the patient, and no other condition that could explain the heart rhythm disturbances was diagnosed. The reporting odds ratio was 3.2 (95% confidence interval, 1.0–10.5). The reporting rate was 2 cases per 100,000 patients treated per year (95% confidence interval, 0.4–6.0). These results suggest a causal relationship between rupatadine and heart rhythm disturbances.Clinical Pharmacology & Therapeutics (2009); 85, 5, 481–484 doi:10.1038/clpt.2008.269 [ABSTRACT FROM AUTHOR]

Colocalization of fluorescent signals in confocal microscopy is usually evaluated by inspecting merged images from different colour channels or by using commercially available software packages. We describe in this paper a simple method for assessment of nuclear localization of proteins in tissue sections through confocal immunolocalization, propidium iodide counterstaining and image analysis. Through a macro command developed for the public domain, Java-based softwareimagej, red, green, blue (RGB) images are automatically split in the red and green channels and a new image composed of the nonblack pixels coincident in both channels is created and inverted for better visualization. This method renders images devoid of both, extranuclear staining and background, thus emphasizing the nuclear signal. The resulting images can easily be used for comparison or quantification of the results. Given the simplicity of the technique and the worldwide diffusion of the software utilized, we think that this method could be useful in order to define standards of colocalization in confocal microscopy. [ABSTRACT FROM AUTHOR]

Circulatory systems of vertebrate and invertebrate metazoans are very different. Large vessels of invertebrates are constituted of spaces and lacunae located between the basement membranes of endodermal and mesodermal epithelia, and they lack an endothelial lining. Myoepithelial differentation of the coelomic cells covering hemal spaces is a frequent event, and myoepithelial cells often form microvessels in some large invertebrates. There is no phylogenetic theory about the origin of the endothelial cells in vertebrates. We herein propose that endothelial cells originated from a type of specialized blood cells, called amoebocytes, that adhere to the vascular basement membrane. The transition between amoebocytes and endothelium involved the acquisition of an epithelial phenotype. We suggest that immunological cooperation was the earliest function of these protoendothelial cells. Furthermore, their ability to transiently recover the migratory, invasive phenotype of amoebocytes (i.e., the angiogenic phenotype) allowed for vascular growth from the original visceral areas to the well-developed somatic areas of vertebrates (especially the tail, head, and neural tube). We also hypothesize that pericytes and smooth muscle cells derived from myoepithelial cells detached from the coelomic lining. As the origin of blood cells in invertebrates is probably coelomic, our hypothesis relates the origin of all the elements of the circulatory system with the coelomic wall. We have collected from the literature a number of comparative and developmental data supporting our hypothesis, for example the localization of the vascular endothelial growth factor receptor-2 ortholog in hemocytes of Drosophila or the fact that circulating progenitors can differentiate into endothelial cells even in adult vertebrates. [ABSTRACT FROM AUTHOR]

Objective To compare transvaginal ultrasound with the Bishop score in assessment of cervical ripening for choice of induction agent. Methods Eighty women were randomized to have preinduction cervical assessment for choice of induction agent based on either Bishop score or transvaginal ultrasound. The primary outcome measure was the percentage of women who were administered prostaglandin as a preinduction agent. The criteria for considering the cervix as unripe and thus for using prostaglandin were either a Bishop score < 6 or a cervical length > 30 mm with cervical wedging of < 30% of the total cervical length. Secondary outcome measures included interval to active phase, interval to delivery and rate of Cesarean section. Results While 85% of women received prostaglauidin in the Bishop score group, only 50% of them did in the transvaginal ultrasound group (P = 0.001). The interval to active phase, interval to delivery and rate of Cesarean section were similar in both groups. Conclusions With the suggested cut-off values of a Bishop score < 6 or a cervical length > 30 mm and wedging < 30%, the use of transvaginal ultrasound instead of Bishop score for preinduction cervical assessment to choose induction agent significantly reduces the need for intracervical prostaglandin treatment without adversely affecting the success of induction. [ABSTRACT FROM AUTHOR]

Modifications in the chloride (mitochondria-rich) and pavement cells of the gill epithelia of the Adriatic sturgeon Acipenser naccarii after their transfer under hypertonic environmental conditions (salinity 35) were examined by light and electron microscopy. In contrast to freshwater specimens, seawater-acclimated fish showed a marked increase in the number and size of chloride cells. Ultrastructural modifications included: presence of a slightly invaginated apical crypt, a darker cytoplasm, a more compact tubular system, a major increase in cisternae from Golgi apparatus stacks and flattened-out sacs with dilated ends that produced an increase in lateral and basal cell surfaces. All these changes indicated enhanced cellular activity. Pavement cells, which largely covered the chloride cells on the gill filament and lamella, exhibited a complex system of microridges on their apical surface. Typical features included numerous desmosomes that characterized the intercellular junction, and the presence in the apical cytoplasm of bundles of filaments and of electro-dense vesicles in freshwater fish or clear vesicles in seawater-acclimated animals. [ABSTRACT FROM AUTHOR]

Objective To analyze the relationship between maternal anxiety and fetal behavior at 15 weeks' gestation. Methods Twenty women in two groups were studied: 10 women underwent amniocentesis and 10 controls did not. Maternal anxiety was evaluated using the State Trait Anxiety Inventory questionnaire. Maternal plasma catecholamines (noradrenaline, adrenaline, dopamine) and maternal serum adrenocorticotropic hormone, cortisol, glucose, insulin, triiodothyronine, thyroxine and thyroidstimulating hormone were measured. Catecholamines were also measured in the amniotic fluid of women undergoing amniocentesis. Compiled actograms of 40rain observations were done using ultrasonography. Results Maternal state-anxiety was significantly increased in the amniocentesis group. Except for fetal hiccups (r = 0.49, P = 0.03) there was no significant correlation between maternal anxiety and any of the other studied fetal movements. Maternal glucose was significantly correlated with hiccups (r = -0.59, P = 0.01), isolated leg movements (r = -0.52, P = 0.03), startles (r = -0.47, P = 0.04) and the total of the studied movements (r = -0.47, P = 0.04). Amniotic fluid catecholamines were significantly correlated with hand-face contact (r = 0.71, P = 0.02 for adrenaline), startles (r = 0.75, P = 0.01 for noradrenaline and r = 0.64, P = 0.04 for dopamine) and general movements (r = 0.89, P = 0.001 for noradrenaline). Conclusions This study does not support a relationship between maternal anxiety and fetal behavior in early pregnancy. Maternal glucose and plasma catecholamines could be related to fetal movements at 15 weeks' gestation. [ABSTRACT FROM AUTHOR]

A response from A. Carvajal, S. Ortega and colleagues to a letter to the editor on their article "Heart Rhythm Disturbances Associated With Rupatadine: A Case Series From the Spanish and Portuguese Pharmacovigilance Systems," published in a previous issue, is presented.

Two species of agarophytes, Gelidium sesquipedale (Clem.) Born. et Thur. and Gracilaria tenuistipitata var. liui (Zhang & Xia), have been cultured in chemostat systems under different light qualities to study the response of growth and polysaccharide yield and composition to certain wavelengths. The yield of galactans, methoxyl groups and sulphate content in the agar as well as the starch concentration of these species are controlled by light quality in a different way, presumably because of their patterns of growth. The polysaccharide characteristics will be discussed in relation to the growth and metabolism of those algae. [ABSTRACT FROM AUTHOR]

Background and Aims: The focus of this paper is on the improvement of substance use disorder (SUD) screening and measurement. Using a multi-dimensional item response theory model, the bifactor model, we provide a psychometric harmonization between SUD, depression, anxiety, trauma, social isolation, functional impairment and risk-taking behavior symptom domains, providing a more balanced view of SUD. The aims are to (1) develop the item-bank, (2) calibrate the item-bank using a bifactor model that includes a primary dimension and symptom-specific subdomains, (3) administer using computerized adaptive testing (CAT) and (4) validate the CAT-SUD in Spanish and English in the United States and Spain., Design: Item bank construction, item calibration phase, CAT-SUD validation phase., Setting: Primary care, community clinics, emergency departments and patient-to-patient referrals in Spain (Barcelona and Madrid) and the United States (Boston and Los Angeles)., Participants/cases: Calibration phase: the CAT-SUD was developed via simulation from complete item responses in 513 participants. Validation phase: 297 participants received the Composite International Diagnostic Interview (CIDI) and the CAT-SUD., Measurements: A total of 252 items from five subdomains: (1) SUD, (2) psychological disorders, (3) risky behavior, (4) functional impairment and (5) social support. CAT-SUD scale scores and CIDI SUD diagnosis., Findings: Calibration: the bifactor model provided excellent fit to the multi-dimensional item bank; 168 items had high loadings (> 0.4 with the majority > 0.6) on the primary SUD dimension. Using an average of 11 items (four to 26), which represents a 94% reduction in respondent burden (average administration time of approximately 2 minutes), we found a correlation of 0.91 with the 168-item scale (precision of 5 points on a 100-point scale)., Validation: strong agreement was found between the primary CAT-SUD dimension estimate and the results of a structured clinical interview. There was a 20-fold increase in the likelihood of a CIDI SUD diagnosis across the range of the CAT-SUD (AUC = 0.85)., Conclusions: We have developed a new approach for the screening and measurement of SUD and related severity based on multi-dimensional item response theory. The bifactor model harmonized information from mental health, trauma, social support and traditional SUD items to provide a more complete characterization of SUD. The CAT-SUD is highly predictive of a current SUD diagnosis based on a structured clinical interview, and may be predictive of the development of SUD in the future., (© 2020 Society for the Study of Addiction.)

Objective: To compare maternal serum leptin concentration in women with pre-eclampsia and women with normal pregnancy, and to evaluate the relationships between leptin and several inflammatory cytokines., Design: Prospective clinical study., Setting: University Hospital of Puerto Real, Cadiz, Spain., Sample: Twenty-seven women with pre-eclampsia and 25 normotensive pregnant women., Methods: Maternal serum levels of TNF-alpha, TGF-beta1, interleukin 6, and leptin were measured using a commercially available immunoassay., Main Outcome Measures: Maternal serum levels of leptin and its relationship to levels of TNF-alpha, TGF-beta1 and interleukin 6., Results: Maternal serum leptin levels were higher in women with pre-eclampsia, but this difference was of borderline statistical significance (median 15.9 ng/mL; interquartile range (5.4-31.9) vs 30.5 ng/mL (13.9-64) (P = 0.05). The concentration of maternal serum leptin was correlated with pre-gestational and gestational body mass index (r = 0.45, P = 0.03; r = 0.44, P = 0.04), TNF-alpha concentration (r = 0.57, P = 0.002) and interleukin-6 level (r = 0.46, P = 0.02) in women with normal pregnancy. In women with pre-eclampsia, only a significant correlation between maternal serum leptin level and TNF-alpha concentration (0.47, P = 0.01) was found., Conclusions: The level of maternal serum leptin is increased and correlates positively with the level of TNF-alpha in women with pre-eclampsia. In women with a normal pregnancy leptin levels not only correlate with TNF-alpha, but also with IL-6 and body mass index.