Determining the perceived acceptability of an intervention designed to improve health literacy around developmentally appropriate play during infancy, with a community advisory group of mothers, in Soweto, South Africa.

Children require opportunities to participate in unstructured, unrestricted active play as infants, to encourage positive health, socioemotional and developmental outcomes in life. Certain social and environmental factors in the home setting can limit participation in play, particularly in low resource settings. As caregivers are their infants' first teachers, they have the important role of providing opportunities and space for children to learn through play.

Protocol for the PLAY Study: a randomised controlled trial of an intervention to improve infant development by encouraging maternal self-efficacy using behavioural feedback.

Introduction: The early infant caregiving environment is crucial in the formation of parent-child relationships, neurobehavioural development and thus child outcomes. This protocol describes the Play Love And You (PLAY) Study, a phase 1 trial of an intervention designed to promote infant development through encouraging maternal self-efficacy using behavioural feedback, and supportive interventions.

Methods And Analysis: 210 mother-infant pairs will be recruited at delivery from community clinics in Soweto, South Africa, and individually randomised (1:1) into two groups.

72 weeks post-partum follow-up of dolutegravir versus efavirenz initiated in late pregnancy (DolPHIN-2): an open-label, randomised controlled study.

Background: Late initiation of antiretrovirals in pregnancy is associated with increased risk of perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy and safety of dolutegravir-based compared with efavirenz-based regimens in mothers and infants.

Methods: DolPHIN-2 was a randomised, open-label trial.

The neurocognition of alexithymia: evidence from neuropsychological and neuroimaging studies.

Objective: Alexithymia refers to an ineffective regulation and expression of emotions. It constitutes a major risk factor for a range of medical and psychiatric problems, including chronic pain, somatisation, anxiety and depression. Alexithymia is a multi-faceted concept, described in terms of cognitive and affective aspects.

Effectiveness of a cognitive-behavioral therapy (CBT) manualized program for clinically anxious children: study protocol of a randomized controlled trial.

Background: In the Netherlands, the prevalence of anxiety disorders is 20%; and children with anxiety are at increased risk for psychopathology throughout adulthood. Recently, a revised version of a cognitive behavioral therapy manualized program called 'Thinking + Doing = Daring' (TDD) was developed for children between 8 and 12 years old with an anxiety disorder. The main aim of this project is to conduct a Randomized Controlled Trial (RCT) to evaluate the effectiveness of TDD.

Platelet concentrate transport in pneumatic tube systems--does it work?

Blood sample transport via pneumatic tube systems (PTS) reduces the turnaround time of laboratories, but it might influence analysis results. Its effect on platelet concentrates (PCs) is not known. Platelet function was investigated after single and multiple PTS transport in comparison with storage and irradiation.

Pharmacokinetics and tolerability of nasal versus intravenous midazolam in healthy Dutch volunteers: a single-dose, randomized-sequence, open-label, 2-period crossover pilot study.

Background: Intranasal (IN) midazolam is a potential alternative to rectal diazepam for the acute treatment of epileptic seizures.

Objective: The purpose of this pilot study was to investigate the pharmacokinetics and tolerability of IN midazolam (50 mg/mL) compared with intravenous (IV) midazolam (2.5 mg) in healthy adult volunteers.

Pharmacokinetics, analgesic effect, and tolerability of a single preprocedural dose of intranasal fentanyl in patients undergoing drain removal after breast reduction or augmentation surgery: A prospective, randomized, double-blind, placebo-controlled study.

Background: Although acetaminophen is used to reduce pain after breast reduction or augmentation surgery, pain during the removal of the surgical drains is typically not specifically treated. Intranasally administered fentanyl may be suitable for pain control during removal of drains. The reported therapeutic window of fentanyl is between 0.

Tyrosine kinase activity of purified recombinant cytoplasmic domain of platelet-derived growth factor beta-receptor (beta-PDGFR) and discovery of a novel inhibitor of receptor tyrosine kinases.

Aberrant expression of platelet-derived growth factor and its receptor (PDGFR) has been implicated in various human disorders, including cardiovascular disease and certain types of cancer. Inhibitors of the tyrosine kinase activity of PDGFR are leads in the development of novel agents to combat these diseases. We describe here a novel, potent inhibitor of PDGFR tyrosine kinase, 3-(4-dimethylamino-benzylidenyl)-2-indolinone (DMBI).

X-ray structure of antistasin at 1.9 A resolution and its modelled complex with blood coagulation factor Xa.

The three-dimensional structure of antistasin, a potent inhibitor of blood coagulation factor Xa, from the Mexican leech Haementeria officinalis was determined at 1.9 A resolution by X-ray crystallography. The structure reveals a novel protein fold composed of two homologous domains, each resembling the structure of hirustasin, a related 55-residue protease inhibitor.

The second Kunitz domain of human tissue factor pathway inhibitor: cloning, structure determination and interaction with factor Xa.

Tissue Factor Pathway Inhibitor (TFPI) is a 36 kDa glycoprotein that helps maintain haemostasis by inhibiting Factor Xa and the Factor VIIa/Tissue Factor (TF) complex. TFPI contains three tandemly linked Kunitz inhibitor domains, of which the second inhibits factor Xa. We have undertaken a multidisciplinary approach to study the structure and function of the second Kunitz domain of TFPI, with a view towards the rational design of factor Xa inhibitors.

Mutational analysis of antistasin, an inhibitor of blood coagulation factor Xa derived from the Mexican leech Haementeria officinalis.

Antistasin is a Factor Xa inhibitor that is present in the salivary glands of the Mexican leech Haementeria officinalis. The antistasin protein consists of 119 amino acids, of which residues 1-55 (domain I) are 56% similar to residues 56-110 (domain II). Of the nine C-terminal amino acids (residues 111-119; domain III), four are positively charged.

The intact and cleaved human antithrombin III complex as a model for serpin-proteinase interactions.

Antithrombin is a member of the serine proteinase inhibitor (serpin) family which contain a flexible reactive site loop that interacts with, and is cleaved by the target proteinase. In cleaved and latent serpins, the reactive site loop is inserted into a large central beta-sheet in the same molecule, whereas in ovalbumin, a nonfunctional serpin, the reactive site loop is completely exposed and in an alpha-helical conformation. However, in neither conformation can the reactive site loop bind to target proteinases.

Influence of temperature and relative humidity on the survival of Chlamydia pneumoniae in aerosols.

The survival of Chlamydia pneumoniae in aerosols was investigated by using a chamber with a capacity of 114.5 liters. We injected 5 x 10(7) inclusion-forming units (IFU) of C.

Crystallization and preliminary crystallographic analysis of antistasin, a leech-derived inhibitor of blood coagulation factor Xa.

The salivary gland of the Mexican leech Haementeria officinalis contains a 15 kDa protein which is a potent and selective inhibitor of factor Xa. It inhibits not only blood coagulation, but also metastasis. A gene, coding for a sequence similar to published antistasin sequences, has been synthesized and expressed in Chinese hamster ovary (CHO) cells.

Dissociation of heparin-dependent thrombin and factor Xa inhibitory activities of antithrombin-III by mutations in the reactive site.

Antithrombin-III (AT-III) is a heparin-dependent inhibitor of thrombin and Factor Xa, two serine proteases that are crucial for blood coagulation. In order to assess whether it would be possible to target AT-III only towards Factor Xa, we replaced parts of the reactive site, or P region, of AT-III by sequences present in prothrombin, a substrate of Factor Xa in the coagulation cascade. We show that replacement of the P3 to P3' region generates the hypothesized phenotype.

Crystallization and preliminary X-ray analysis of human antithrombin III.

Human antithrombin III has been crystallized from 18 to 21% (w/v) polyethylene glycol 4000 at pH 7.15. The spacegroup is P2(1) with cell parameters a = 89.

A microELISA system for the detection of both anti-HIV-1 and anti-HIV-2 antibodies.

Current anti-HIV-1 screening tests combine an excellent anti-HIV-1 sensitivity with a sensitivity of only 28-93% for anti-HIV-2 positive plasma or serum samples. The reactivity of anti-HIV-2 sera in anti-HIV-1 screening tests is based mainly on the immunological cross-reactivity of the GAG and POL proteins of HIV-1 and HIV-2. We describe here a sandwich immunoassay, in which HIV-1 viral lysate is combined with an HIV-2 ENV synthetic peptide, corresponding to the immunodominant envelope epitope, as the coating antigens on microELISA plates.

The Wnt-1 (int-1) oncogene promoter and its mechanism of activation by insertion of proviral DNA of the mouse mammary tumor virus.

Wnt-1 (int-1) is a cellular oncogene often activated by insertion of proviral DNA of the mouse mammary tumor virus. We have mapped the 5' end and the promoter area of the Wnt-1 gene by nuclease protection and primer extension assays. In differentiating P19 embryonal carcinoma cells, in which Wnt-1 is naturally expressed, two start sites of transcription were found, one preceded by two TATA boxes and one preceded by several GC boxes.

Phorbol ester-inducible T-cell-specific expression of variant mouse mammary tumor virus long terminal repeats.

Acquired proviruses of mouse mammary tumor virus (MMTV) in T-cell leukemias of male GR mice have rearrangements in the U3 region of their long terminal repeats (LTR). In contrast to the endogenous nonrearranged MMTV proviruses, these mutated copies are highly expressed in leukemic T cells. To investigate whether the sequence alterations in the LTR are responsible for the high expression of rearranged MMTV proviruses, we made constructs in which normal and variant LTRs drive the bacterial reporter gene chloramphenicol acetyltransferase (CAT).

New developments in ELISA verification of anti-HIV screening of blood donors.

First generation ELISA screening assays for antibodies to HTLV-III (HIV) generated between 0.1 and 1.0% false positive results.

Acetylation of melanocyte-stimulating hormone and beta-endorphin in the pars intermedia of the perinatal pituitary gland in the mouse.

This report concerns ontogenetic aspects of the production and in vitro release of NH2-terminally acetylated forms of melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin by the pars intermedia of the pituitary gland of the mouse. In vitro biosynthetic analysis and radioimmunoassay revealed that approximately 12 h before birth most of the MSH in the fetal pars intermedia is present as des-N alpha-acetyl alpha-MSH. The same non-acetylated peptide is at this stage also the major release form of melanotropin.