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.

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.

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.

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.

[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.

[Involvement of nonhypothalamic encephalic structures in the Hand-Schüller-Christian disease. Report of a case and review of the literature]. / Comprometimento de estruturas encefalicas não hipotalamicas na molestia de Hand-Schüller-Christian. Relato de caso e revisão da literatura

A case of Hand-Schüller-Christian disease which presented a pyramidal syndrome besides elements of the classical triad and concentric retraction of the visual field is reported. The rare involvement of non-hypothalamic encephalic structures in that disease is emphasized together with the favourable effect of corticotherapy and radiotherapy.

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.

[Alexia without agraphia: a clinico-tomographic study]. / Alexia sem agrafia: estudo clínico-tomográfico.

The authors report the clinical findings and CT-scanning results in two cases of alexia without agraphia and review the literature on this subject. Both patients had extensive infarction in the territory supplied by the left posterior cerebral artery and developed severe alexia without agraphia, right hemianopia without color-anomia and one of them presented with transient verbal memory difficulties. In both cases the evolution was very good, with total regression of the alexia after 17 months in the first patient and almost complete recovery after there months in the second one. The authors comment on the causes and possible mechanisms of the alexias, especially of the alexia without agraphia, and suggest that every patient with right hemianopic disturbances due to occlusion of the left posterior cerebral artery be thoroughly studied from a neurological point of view, so that this syndrome can be detected since, notwithstanding its recognized rarity, it seems highly probable that many cases have been overlooked as a result of incomplete examination of the patients.

[Isaacs' syndrome. Report of a case and review of the literature]. / Sindrome de Isaacs. Registro de um caso e revisão da literatura

The case of a 17-year-old boy who had been well until the age of four when progressive stiffness of lower limbs developed is reported. Soon walking became difficult and on on his thighs, buttocks and calves one could notice the appearance of myokymia. Painful and intermittent spasms were often present specially after physical strain. This was followed by profuse sweating. Strength was normal but muscle relaxing was slow mainly in the quadriceps. The familiar history for neuromuscular pathology was negative. Muscle enzymes, thyroid function tests were within normal limits and muscular biopsy showed no abnormalities. The EMG disclosed a permanent spontaneous activity, more evident in the quadriceps, which was normal in shape, amplitude and duration. In association to this activity multiplets discharges and low motor units were also observed; in interferencial pattern appeared at maximum contraction but the multiplets and low motor units potentials kept on showing even though voluntary muscular activity ceased. The therapeutic essay with carbamazepin had a dramatic effect upon the course of the patient's conditions. He showed a great improvement with this drug and today leads a normal life being able even to play soccer and ride a bicycle. An interesting remark which should be done is the fact that the flexion of the neck inhibits the quadriceps myokymia whereas the extension makes them to appear and even worsen. Unfortunately is was not possible to carry out a more accurate investigation concerning electropharmacology and hystopathology as the patient was uncooperative and refused to undergo such examinations. However the authors believe that this clinical picture can be considered as a case of "continuous muscle-fibre activity" due to the great similarity it bears to the cases related by Isaacs in 1961. An extensive review concerning the pertinent literature has been done.

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.

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.

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.

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.

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.