Screening for pre-eclampsia at 11-13 weeks' gestation: use of pregnancy-associated plasma protein-A, placental growth factor or both.

OBJECTIVE: First-trimester screening for pre-eclampsia (PE) is useful because treatment of the high-risk group with aspirin reduces the rate of early PE with delivery at < 34 weeks' gestation by about 80% and that of preterm PE with delivery at < 37 weeks by 60%. In previous studies, we reported that the best way of identifying the high-risk group is by a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF). An alternative biochemical marker is pregnancy-associated plasma protein-A (PAPP-A), which is used widely as part of early screening for trisomy. The objective of this study was to examine the additive value of PlGF and PAPP-A in first-trimester screening for preterm PE by maternal factors, MAP and UtA-PI and define the risk cut-off and screen-positive rate to achieve a desired detection rate of PE if PAPP-A rather than PlGF was to be used for first-trimester screening. METHODS: This was a non-intervention screening study. The data were derived from prospective screening for adverse obstetric outcomes in women with singleton pregnancy attending for a routine first-trimester hospital visit. Patient-specific risks of delivery with PE at < 37 weeks' gestation were calculated using the competing-risks model to combine the prior distribution of gestational age at delivery with PE, obtained from maternal characteristics and medical history, with multiples of the median (MoM) values of MAP, UtA-PI, PlGF and PAPP-A. The performance of screening in the total population and in subgroups of women of white and black racial origin was estimated. McNemar's test was used to compare the detection rate, for a fixed screen-positive rate, of screening with and without PlGF and PAPP-A. Risk cut-offs and screen-positive rates to achieve desired detection rates of preterm PE were determined in screening with and without PlGF and PAPP-A. RESULTS: The study population was composed of 60 875 singleton pregnancies, including 1736 (2.9%) that developed PE. There are three main findings of this study. First, the performance of first-trimester screening for PE by a combination of maternal factors, MAP, UtA-PI and PlGF is superior to that of screening by maternal factors, MAP, UtA-PI and PAPP-A; for example, in screening by maternal factors, MAP, UtA-PI and PlGF, at a screen-positive rate of 10%, the detection rate of PE with delivery at < 37 weeks' gestation was 74.1%, which was 7.1% (95% CI, 3.8-10.6%) higher than in screening by maternal factors, MAP, UtA-PI and PAPP-A. Second, addition of serum PAPP-A does not improve the prediction of PE provided by maternal factors, MAP, UtA-PI and PlGF. Third, the risk cut-off and screen-positive rate to achieve a given fixed detection rate of preterm PE vary according to the racial composition of the study population and whether the biomarkers used for screening are MAP, UtA-PI and PlGF or MAP, UtA-PI and PAPP-A. For example, in screening by a combination of maternal factors, MAP, UtA-PI and PlGF in white women, if the desired detection rate of preterm PE was 75%, the risk cut-off should be 1 in 136 and the screen-positive rate would be 14.1%; in black women, to achieve a detection rate of 75%, the risk cut-off should be 1 in 29 and the screen-positive rate would be 12.5%. In screening by a combination of maternal factors, MAP, UtA-PI and PAPP-A in white women, if the desired detection rate of preterm PE was 75%, the risk cut-off should be 1 in 140 and the screen-positive rate would be 16.9%; in black women, to achieve a detection rate of 75%, the risk cut-off should be 1 in 44 and the screen-positive rate would be 19.3%. CONCLUSION: In first-trimester screening for PE, the preferred biochemical marker is PlGF rather than PAPP-A. However, if PAPP-A was to be used rather than PlGF, the same detection rate can be achieved but at a higher screen-positive rate. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Genome-wide analysis highlights genetic dilution in Algerian sheep.

Algeria represents a reservoir of genetic diversity with local sheep breeds adapted to a large range of environments and showing specific features necessary to deal with harsh conditions. This remarkable diversity results from the traditional management of dryland by pastoralists over centuries. Most of these breeds are poorly productive, and the economic pressure leads farmers to realize anarchic cross-breeding (that is, not carried out in the framework of selection plans) with the hope to increase animal's conformation. In this study, eight of the nine local Algerian sheep breeds (D'men, Hamra, Ouled-Djellal, Rembi, Sidaoun, Tazegzawt, Berber and Barbarine) were investigated for the first time by genome-wide single-nucleotide polymorphism genotyping. At an international scale, Algerian sheep occupied an original position shaped by relations with African and European (particularly Italian) breeds. The strong genetic proximity with Caribbean and Brazilian breeds confirmed that the genetic make-up of these American breeds was largely influenced by the Atlantic slave trade. At a national scale, an alarming genetic dilution of the Berber (a primitive breed) and the Rembi was observed, as a consequence of uncontrolled mating practices with Ouled-Djellal. A similar, though less pronounced, phenomenon was also detected for the Barbarine, another ancestral breed. Genetic originality appeared to be better preserved in Tazegzawt, Hamra, D'men and Sidaoun. These breeds should be given high priority in the establishment of conservation plans to halt their progressive loss. For Berber and Barbarine that also occur in the bordering neighbor countries, urgent concerted transnational actions are needed.

Machine learning techniques and drug design.

The interest in the application of machine learning techniques (MLT) as drug design tools is growing in the last decades. The reason for this is related to the fact that the drug design is very complex and requires the use of hybrid techniques. A brief review of some MLT such as self-organizing maps, multilayer perceptron, bayesian neural networks, counter-propagation neural network and support vector machines is described in this paper. A comparison between the performance of the described methods and some classical statistical methods (such as partial least squares and multiple linear regression) shows that MLT have significant advantages. Nowadays, the number of studies in medicinal chemistry that employ these techniques has considerably increased, in particular the use of support vector machines. The state of the art and the future trends of MLT applications encompass the use of these techniques to construct more reliable QSAR models. The models obtained from MLT can be used in virtual screening studies as well as filters to develop/discovery new chemicals. An important challenge in the drug design field is the prediction of pharmacokinetic and toxicity properties, which can avoid failures in the clinical phases. Therefore, this review provides a critical point of view on the main MLT and shows their potential ability as a valuable tool in drug design.

Excitation energies from ground-state density-functionals by means of generator coordinates.

The generator-coordinate method is a flexible and powerful reformulation of the variational principle. Here we show that by introducing a generator coordinate in the Kohn-Sham equation of density-functional theory, excitation energies can be obtained from ground-state density functionals. As a viability test, the method is applied to ground-state energies and various types of excited-state energies of atoms and ions from the He and the Li isoelectronic series. Results are compared to a variety of alternative DFT-based approaches to excited states, in particular time-dependent density-functional theory with exact and approximate potentials.

Generator coordinate method in time-dependent density-functional theory: memory made simple.

The generator coordinate (GC) method is a variational approach to the quantum many-body problem in which interacting many-body wave functions are constructed as superpositions of (generally nonorthogonal) eigenstates of auxiliary Hamiltonians containing a deformation parameter. This paper presents a time-dependent extension of the GC method as a new approach to improve existing approximations of the exchange-correlation (XC) potential in time-dependent density-functional theory (TDDFT). The time-dependent GC method is shown to be a conceptually and computationally simple tool to build memory effects into any existing adiabatic XC potential. As an illustration, the method is applied to driven parametric oscillations of two interacting electrons in a harmonic potential (Hooke's atom). It is demonstrated that a proper choice of time-dependent generator coordinates in conjunction with the adiabatic local-density approximation reproduces the exact linear and nonlinear two-electron dynamics quite accurately, including features associated with double excitations that cannot be captured by TDDFT in the adiabatic approximation.

A chemometric study of megazol derivatives with activity against Trypanosoma equiperdum.

The AM1 semiempirical method was employed to study megazol and 13 of its analogues where their activity against Trypanosoma equiperdum was obtained from in vitro tests. Several molecular properties (descriptors or variables) were calculated for the 14 compounds studied to be correlated with the biological activity. For a practical analysis of large data sets, it is necessary to reduce the dimensionality and select the most relevant descriptors related to the biological activity under study. For this purpose, the following chemometric methods were employed: principal component analysis (PCA), hierarchical cluster analysis (HCA), K-nearest neighbour (KNN), stepwise discriminant analysis (SDA) and soft independent modelling of class analogy (SIMCA). These methods showed that the descriptors molecular electronic energy (Eelet), charge on the first nitrogen at substituent 2 (qN), volume of substituent at C5 position (V-S5), dihedral angle (D3) and bond length between atom C4 and its substituents (L4) are responsible for the separation between active and inactive compounds against T. equiperdum.

A structure-activity relationship study of quinone compounds with trypanocidal activity.

A set of 25 quinone compounds with anti-trypanocidal activity was studied by using the density functional theory (DFT) method in order to calculate atomic and molecular properties to be correlated with the biological activity. The chemometric methods principal component analysis (PCA), hierarchical cluster analysis (HCA), stepwise discriminant analysis (SDA), Kth nearest neighbor (KNN) and soft independent modeling of class analogy (SIMCA) were used to obtain possible relationships between the calculated descriptors and the biological activity studied and to predict the anti-trypanocidal activity of new quinone compounds from a prediction set. Four descriptors were responsible for the separation between the active and inactive compounds: T5 (torsion angle), QTS1 (sum of absolute values of the atomic charges), VOLS2 (volume of the substituent at region B) and HOMO-1 (energy of the molecular orbital below HOMO). These descriptors give information on the kind of interaction that occurs between the compounds and the biological receptor. The prediction study was done with a set of three new compounds by using the PCA, HCA, SDA, KNN and SIMCA methods and two of them were predicted as active against the Trypanosoma cruzi.

Synthesis, structure, electronic and vibrational spectra of 9-(Diethylamino)-benzo(a)phenoxazin-7-ium-5-N-methacrylamide.

The electronic and vibrational spectra of 9-(Diethylamino)-benzo(a)phenoxazin-7-ium-5-N-methacrylamide (Nile Blue-5-N-methacrylamide) are measured, and the results are compared with the theoretical values obtained by quantum chemical calculations. The geometry, electronic transitions, charge distribution, and the IR normal modes of this new dye and of its precursor Nile Blue have been computed by using Density Functional Theory (DFT) method with the functional B3LYP and the 6-31G(d) Gaussian basis set. The molecular properties of the two dyes, predicted and observed, are very similar in the electronic ground state. In the excited state, however, the longer lifetime and larger fluorescence quantum yield of the Nile Blue-5-methacrylamide is ascribed to an inhibition of the twisted intramolecular charge transfer (TICT) process, when the NH2 is substituted by the methacrylamide in the 5-position of the aromatic extended ring of the dye. The change in charge density of the N atom in 5-position, as well as the difference in dipole moment and ionization potential of the two dyes molecules, explain the attenuation of TICT process. The vibration spectra of both dyes are simulated properly by using the DFT method.

The use of the qualitative research interview to uncover the essence of community psychiatric nursing: methodological reflections.

During the last decade in the Nordic countries, the qualitative research interview (QRI) has become a fruitful method for the study of how people experience their life-world, especially in social and professional contexts. The essential features and structural components of the QRI have been well developed, and various aspects of the interpretation of interview texts have been analyzed and theoretically assessed from the hermeneutic-phenomenological point of view. The validity, reliability, and fruitfulness of the method also have been constructively scrutinized. The present study, which examines the choice of appropriate QRI strategy and technique as illustrated with concrete examples, focuses on the specific area of psychiatric nurses' professional thoughts and experiences in community psychiatric nursing. This scientific article seeks to stimulate and illuminate the right use of QRI.

Squamous cell carcinoma-like and pox lesions occurring simultaneously in chorioallantoic membranes of chicken embryos inoculated with materials from squamous cell carcinoma and pox lesions in broiler chickens.

The finding of closely associated squamous cell carcinoma (SCC)-like lesions and pox lesions in chorioallantoic membranes (CAMs) inoculated with skin and palate samples taken from broilers is described. The samples were obtained from two broilers coming from different flocks that were not vaccinated against fowl pox. Both birds presented skin lesions, which were diagnosed in one bird as fowl pox, and in the other as SCC. After inoculation of CAMs with fresh tissues from both birds, histologic examination revealed, in all CAMs, lesions that were characteristic of fowl pox together with lesions consistent with those seen in the skin of broilers affected with SCC. This finding was unexpected and may shed some light on the etiology of SCC.

The role of virtue ethics in psychiatric nursing.

The main purpose of this article is to discuss the place of the ethics of virtues and character in nursing and health care in general, and in psychiatric nursing in particular. To attain this goal, the relationship between the ethics of duty (i.e. rule based ethics) and the ethics of virtue and character will be clarified in order to defend our main hypothesis that these two types of ethics should complement each other, since both are necessary but neither by itself is sufficient for nursing. This means that any applied ethics, as in nursing, should consider the importance of the agent's moral character. To support our arguments, we shall use cases from the empirical reality of psychiatric and mental health care.

An analysis of some dimensions of the concept of moral sensing exemplified in psychiatric care.

There are few studies that focus on the interpersonal aspect of everyday ethical conflicts. Conceptual frameworks for research into ethical decision making in the health care system are mainly based on an ethic in which objectivity and principle-based thinking is emphasized, leaving the experience of concrete moral conflicts relatively unexplored. The aim of this paper is to analyze the dimensions of "moral sensing," a concept identified in an earlier grounded theory study of psychiatric nursing. Four dimensions of the concept of moral sensing, i.e., feeling, intuition, benevolence and genuineness, were synthesized by reviewing the works of past and contemporary philosophers. The analysis of moral sensing and its dimensions is exemplified by actual nurse-patient encounters in psychiatric nursing practice.

[Kinetic distribution of cyclosporine after single dose subcutaneous administration; experimental study in rats]. / Disposição cinética da ciclosporina após administração de dose única subcutânea; estudo experimental em ratos.

Adequate dose of cyclosporin A shows immunosuppressor effect, and low toxicity. The doses reported previously ranged from 2.5 to 25 mg/kg every 24, 48 hours and even 7 days. Routes for cyclosporin A administration are subcutaneous or intramuscular preferentially. In the present study, cyclosporin A (CSA) single dose subcultaneous was administered to 21 Wistar-Furth rats, adult, males, weighing 350-450g. The animals were divided in 3 groups receiving 2.5 mg/kg (group 1), 5.0 mg/kg (group 2) and 10.0 mg/kg (group 3). Blood samples were collected at 1, 4, 8, 12, 24, 48 and 72 hours after drug collection into plastic tubes containing sodium EDTA. Blood cyclosporin A levels were determined by a commercially available radioimmunoassay kit (Sandoz RIE Kit Basel) after whole hemolysis using liquid nitrogen. Cyclosporin A blood concentrations vs time curve were plotted (log C vs t). Two compartment open model was applied to estimate the kinetic parameters as t(1/2) beta e beta. A model independent calculation was applied to estimate the kinetic parameters as AUCT, CIT and Vd. Initially, parametric and nonparametric tests were applied. Due to the high dispositional variability, nonparametric statistics (Wilcoxon's test) was applied for analysis of results obtained. Based on data obtained in the present study the authors suggest linear pharmacokinetics where Cmax AUCT showed proportional increases with the dose administered, remaining unchanged the Kinetic parameters as t(1/2) B,B, CIT and Vd.

EEG and dementia indicators in AIDS patients' Rorschach test.

We studied the EEG and Rorschach test (RT) of nineteen AIDS patients and eight normal people in the same age group. Eight patients presented slow alpha rhythms (8 to 9 Hz); three, not-slow alpha rhythms (> 9 to 13 Hz); and eight, beta rhythms in background activity. Paroxystic activity, characterized by diffuse theta or delta waves, was present in eleven patients. We observed Oberholzer syndrome (organic dementia diagnosed by RT) in ten patients and Piotrowski syndrome (organic dementia diagnosed by RT) in eleven patients; six presented both. When considering only the group of AIDS patients, we did not observe a significant relation among slow alpha rhythm, not-slow alpha rhythm and the presence of paroxystic activity with the above-mentioned syndromes. AIDS patients with slow alpha rhythms showed a significantly greater number of Piotrowski syndrome dementia indicators when compared to normal individuals or those with slow alpha rhythms. We did not observe the same with Oberholzer syndrome.

A holistic-existential model for psychiatric nursing.

The authors offer a holistic model for psychiatric nursing based on a existential concept of man. They assert that the biomedical model of health and sickness is not sufficient to understand the reality in which psychiatric nurses practice. Within this model, understanding clients in relation to their life contexts becomes the focus, as well as trying to comprehend what effects suffering has on their ability to function. The relationship between nurse and client is discussed from a point of view that considers central existential precepts, such as: equality, encounter/being present, self-esteem/significance, responsibility and choice, objectives, meaning and clarification of values, guilt and atonement, openness and insight, conformity versus rebellion and finally hope.

Electroencephalogram base rhythm in AIDS patients.

We studied the EEG of 73 patients diagnosed with HIV infection, with or without secondary complications. Sixty-eight belonged to CDC (Center for Disease Control) group IV and 38 presented signs or symptoms of encephalic neurological impairment. Rhythms constituting base activity were alpha (65.75%), beta (13.70%), theta (12.33%), and delta (8.22%). The alpha rhythm presented two modes: slow (8 to 9 Hz) in 25/48 or 52.08% of the cases and not-slow (> 9 to 13 Hz) in 23/48 or 47.92% of the cases. The alpha slow-mode has been observed in about 10 to 15% of the normal population, with the 8 Hz frequency being found in only 1% of the normal adult population, which suggests that in some manner HIV is implicated in the slowing-down of the EEG base rhythm in AIDS patients. The patients from CDC group IV with encephalic neurological involvement presented a base rhythm significantly lower than those with non-encephalic involvement or the absence of neurological impairment.

Photoparoxysmal responses.

Sixty-five outpatients with photoparoxysmal response (PPR) during routine EEG were studied. The PPR showed prevalence in women (75.4%). Seizures were found in 66.1% of cases. The rest recordings were abnormal in 41.8% with prevalence of generalized paroxysm. Eight patterns of PPR were observed, being polyspike mixed to slow wave the most frequent (53%). The epileptic group showed a bimodal distribution in the several bands of photic stimulation, near 8 and 20-24 Hz. A sustained paroxysmal abnormality persisting after the photic stimulation was present in 6 epileptic patients.

[Periodic lateralized epileptiform discharges. II. Developmental aspects]. / Descargas epileptiformes periódicas lateralizadas. II. Aspectos evolutivos.

A investigation was done on EEG evolution of 9 patients with PLEDs. In all patients PLEDs eventually disappeared, in general in a short period, less than 4 days in 5 cases. In 4 cases evolution was to slow background activity, and to posterior normalization in 2. In 3 cases evolution was to delta activity and suppression bursts, and all the 3 patients died. In the last 2 patients PLEDs were replaced by localized paroxysmal activity, which was anteriorly registered in 1. PLEDs was found in acute dysfunction of CNS, and in epileptic patients in periods of increased seizure activity. These data suggest that a critical point of alteration of the normal neuronal activity is needed for appearance and maintenance of PLEDs. No correlation could be done between the evolution of PLEDs, always to disappearance, and clinical outcome, that was variable.

[Periodic lateralized epileptiform discharges. I. Clinical and electroencephalographic aspects]. / Descargas epileptiformes periódicas lateralizadas. 1. Aspectos clínicos e eletrencefalográficos.

In a two-years period, from a total of 5481 EEGs, we could select 25, corresponding to 22 patients, with PLEDs (prevalence of 0.45%). The group was composed by 13 males and 9 females, with age ranging from 5 months to 85 years. Main diagnosis was epilepsy of unknown etiology and brain tumor (22% each). The localization of PLEDs was mainly temporal region (54% of the whole group) and more frequent morphology was "delta triphasic wave" (a graphic pattern resembling sharp wave, but with longer duration) (1/3 of total), followed by sharp biphasic wave and sharp wave-slow wave (29% each). Although 9 patients died it was not possible to determine prognostic value of PLEDs specifically for each pathological condition.

Illiteracy and brain damage. 2. Manifestations of unilateral neglect in testing "auditory comprehension" with iconographic materials.

This report concerns the sentence-picture matching behavior of 100 neurologically healthy and 169 brain-damaged subjects, all of whom were unilingual adult right-handers. Within this population, 144 subjects were totally unschooled illiterates and the remaining 125 had received school education and thereafter had retained writing skills and reading habits. Brain-damaged subjects were tested less than 2 months after a first left- or right-hemisphere stroke. All subjects were administered an aphasia screening battery including, among other subtests, a set of six sentence-picture matching stimuli. For each of these six stimuli, subjects heard a sentence uttered by the examiner and were then requested to match this sentence with one of four drawings presented within a single display divided into four quadrants of equal surface. Three sentences were syntactically "simple" (noun subject + verb) and three were relatively more "complex" (noun subject + verb + one or two noun complements). Evidence of unilateral neglect was found in both left- and right-brain-damaged illiterates and literates. Moreover, the right neglect of left-brain-damaged subjects was manifest mostly when target sentences were relatively "complex" whereas the left neglect of right-brain-damaged subjects was manifest irrespective of the syntactic complexity of target sentences. Our data are interpreted as indicative of an interaction between two cognitive disorders resulting from dysfunctions of asymmetrically represented cognitive mechanisms. The implications of these findings with respect to clinical and research aphasia testing are discussed.