The "Happy-Mums" website dedicated to the perinatal period: Evaluation of its acceptability by parents and professionals.

OBJECTIVE: Pregnancy and childbirth are associated with new needs for mothers, especially an eagerness for information. The aim of this study was to evaluate whether the Happy-Mums.be website meets the expectations and needs of its future users. DESIGN: After the development of the Happy-Mums.be website, it was submitted to parents and professionals and evaluated by an online survey, which consisted of the third round of an ongoing Delphi survey. SETTING AND PARTICIPANTS: The panel involved in the survey included parents (both mothers and fathers) and professionals (health professionals and early childhood professionals, orbiting mothers of children aged 0-2 years). FINDINGS: Twenty-eight parents and professionals participated in the third round of the Delphi survey. The participants indicated that Happy-Mums.be was useful and easy to use. They attributed a mean score of 8 out of 10 for the content, design and quality of the information on the Happy-Mums.be website. The majority of participants said that they would recommend the website both during pregnancy and the postnatal period. CONCLUSIONS: Happy-Mums.be meets the needs and expectations of parents and professionals in terms of both content and design. More specifically, the quality of the information found on Happy-Mums.be was judged to be significantly better than the information found on other websites.

What should a website dedicated to the postnatal period contain? A Delphi survey among parents and professionals.

OBJECTIVES: Mothers have a great need for information during the postnatal period. Trying to meet this need, mothers are increasingly turning to the Internet. Nevertheless, many women have stated that they often or always found that the information that they found on the Internet was incomplete or wrong. Many women therefore believe that health professionals should suggest reliable Internet websites for new mothers. The aim of this study was therefore to find a consensus on the content of a reliable and centralized website dedicated to mothers from the end of pregnancy to 1 year after childbirth. DESIGN: Two rounds of an online Delphi survey were used in this study. SETTING AND PARTICIPANTS: The panel of participants involved in the survey included parents (both mothers and fathers) and professionals (health professionals and professionals of early childhood for mothers of children aged 0 to 2 years). FINDINGS: Ninety-six parents and professionals participated in the first round (37.7 ± 9.76 years; 84.4% of women) and 78 in the second round. The majority of participants (94.6%) thought that a centralized website could help mothers from pregnancy to one year after childbirth. The content that the experts would like to find on a website were themed into five categories: "infants' information", "parents' information", "administrative information", "professionals' information" and "type of resources". In each category, experts highlighted the key words that they found important and should be reported on the website. The most important items highlighted by participants were baby's feeding/breastfeeding (92.8%), babies' needs (84.1%), baby blues (77.9%), postpartum depression (72.1%), management of the couple's relationship (72.1%), women's right to postnatal care (83.6%), links to reliable documents (63.9%) and a list of useful contacts (52.5%). CONCLUSIONS: This study helped to understand the questions that mothers ask themselves during the postpartum period and provided priorities to respond to their questions in the process of developing a website.

Identifying maternal needs following childbirth: A qualitative study among mothers, fathers and professionals.

BACKGROUND: Pregnancy and childbirth are two critical stages in a woman's life. Various studies have suggested that psychological distress is common during the year after childbirth. The objectives of this exploratory study were (1) to explore the needs of mothers in the year following childbirth; (2) to compare these needs between mothers who did not have the feeling of living a psychological disorder or a depression and mothers who lived a psychological disorder or had the impression of living a depression; and (3) to compare the needs expressed by mothers with the perception of professionals and fathers about the mothers' needs. METHODS: First, we proceeded to 22 individual qualitative interviews followed by one focus group, with mothers, with and without experience of psychological distress. Then, we conducted 2 focus groups: one with professionals and one with fathers. RESULTS: Needs of mothers after childbirth have been indexed in four categories: need of information, need of psychological support, need to share experience, and need of practical and material support. Women do not feel sufficiently informed about this difficult period of life. They do not feel sufficiently supported, not only from a psychological point of view but also from a more practical point of view, for example with household chores. They need to share their experience of life, they need to be reassured and they need to feel understood. It seems that some differences exist between mothers' and professionals' experiences but also between mothers' and fathers' experiences. CONCLUSION: Young mothers apparently feel a lack of support at different levels in the year following childbirth. This study provides ways to meet women's needs and to try to prevent the risk of postpartum psychological distress during this period of time.

TLEM 2.0 - a comprehensive musculoskeletal geometry dataset for subject-specific modeling of lower extremity.

When analyzing complex biomechanical problems such as predicting the effects of orthopedic surgery, subject-specific musculoskeletal models are essential to achieve reliable predictions. The aim of this paper is to present the Twente Lower Extremity Model 2.0, a new comprehensive dataset of the musculoskeletal geometry of the lower extremity, which is based on medical imaging data and dissection performed on the right lower extremity of a fresh male cadaver. Bone, muscle and subcutaneous fat (including skin) volumes were segmented from computed tomography and magnetic resonance images scans. Inertial parameters were estimated from the image-based segmented volumes. A complete cadaver dissection was performed, in which bony landmarks, attachments sites and lines-of-action of 55 muscle actuators and 12 ligaments, bony wrapping surfaces, and joint geometry were measured. The obtained musculoskeletal geometry dataset was finally implemented in the AnyBody Modeling System (AnyBody Technology A/S, Aalborg, Denmark), resulting in a model consisting of 12 segments, 11 joints and 21 degrees of freedom, and including 166 muscle-tendon elements for each leg. The new TLEM 2.0 dataset was purposely built to be easily combined with novel image-based scaling techniques, such as bone surface morphing, muscle volume registration and muscle-tendon path identification, in order to obtain subject-specific musculoskeletal models in a quick and accurate way. The complete dataset, including CT and MRI scans and segmented volume and surfaces, is made available at http://www.utwente.nl/ctw/bw/research/projects/TLEMsafe for the biomechanical community, in order to accelerate the development and adoption of subject-specific models on large scale. TLEM 2.0 is freely shared for non-commercial use only, under acceptance of the TLEMsafe Research License Agreement.

Evaluation of a morphing based method to estimate muscle attachment sites of the lower extremity.

To generate subject-specific musculoskeletal models for clinical use, the location of muscle attachment sites needs to be estimated with accurate, fast and preferably automated tools. For this purpose, an automatic method was used to estimate the muscle attachment sites of the lower extremity, based on the assumption of a relation between the bone geometry and the location of muscle attachment sites. The aim of this study was to evaluate the accuracy of this morphing based method. Two cadaver dissections were performed to measure the contours of 72 muscle attachment sites on the pelvis, femur, tibia and calcaneus. The geometry of the bones including the muscle attachment sites was morphed from one cadaver to the other and vice versa. For 69% of the muscle attachment sites, the mean distance between the measured and morphed muscle attachment sites was smaller than 15 mm. Furthermore, the muscle attachment sites that had relatively large distances had shown low sensitivity to these deviations. Therefore, this morphing based method is a promising tool for estimating subject-specific muscle attachment sites in the lower extremity in a fast and automated manner.

In vitro validation and reliability study of electromagnetic skin sensors for evaluation of end range of motion positions of the hip.

There is growing evidence that femoroacetabular impingement (FAI) is a probable risk factor for the development of early osteoarthritis in the nondysplastic hip. As FAI arises with end range of motion activities, measurement errors related to skin movement might be higher than anticipated when using previously reported methods for kinematic evaluation of the hip. We performed an in vitro validation and reliability study of a noninvasive method to define pelvic and femur positions in end range of motion activities of the hip using an electromagnetic tracking device. Motion data, collected from sensors attached to the bone and skin of 11 cadaver hips, were simultaneously obtained and compared in a global reference frame. Motion data were then transposed in the hip joint local coordinate systems. Observer-related variability in locating the anatomical landmarks required to define the local coordinate system and variability of determining the hip joint center was evaluated. Angular root mean square (RMS) differences between the bony and skin sensors averaged 3.2° (SD 3.5°) and 1.8° (SD 2.3°) in the global reference frame for the femur and pelvic sensors, respectively. Angular RMS differences between the bony and skin sensors in the hip joint local coordinate systems ranged at end range of motion and dependent on the motion under investigation from 1.91 to 5.81°. The presented protocol for evaluation of hip motion seems to be suited for the 3-D description of motion relevant to the experimental and clinical evaluation of femoroacetabular impingement.

A method for three-dimensional evaluation and computer aided treatment of femoroacetabular impingement.

Several theoretical models have shown that the range of motion of the hip joint is impaired in patients with femoroacetabular impingement, and that the acetabular cartilage is at risk of being damaged as a result of abnormal shear stresses, even during normal everyday activities. Computer aided technologies might add to the early diagnosis and adequate treatment of such lesions. This paper describes the technique, theories and algorithms we have developed for patient-specific detection, analysis and computer aided surgery of femoroacetabular impingement. Currently available models applicable to femoroacetabular impingement offer modeling based on collision analysis of a constrained hip joint. Such an approach implies that neither the femur nor the acetabulum can be analyzed completely separately for the presence of structural lesions responsible for the impingement problem. Moreover, a constrained model does not allow for comprehensive prediction of the possible locations and extent of secondary cartilage lesions (so-called contre-coup lesions) of the posterior acetabulum opposite the anterior impingement site. We report a new technique for the subject-specific morphological analysis of the proximal femur, acetabulum and hip joint. The technique offers a number of advantages compared to currently used techniques for the diagnosis and evaluation of hip impingement, and has direct orthopaedic applications as it allows computer aided planning and minimally invasive surgery for patients with femoroacetabular impingement.

Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial.

BACKGROUND: RTS,S/AS02 is a pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein of Plasmodium falciparum fused to HBsAg, incorporating a new adjuvant (AS02). We did a randomised trial of the efficacy of RTS,S/AS02 against natural P. falciparum infection in semi-immune adult men in The Gambia. METHODS: 306 men aged 18-45 years were randomly assigned three doses of either RTS,S/AS02 or rabies vaccine (control). Volunteers were given sulfadoxine/pyrimethamine 2 weeks before dose 3, and kept under surveillance throughout the malaria transmission season. Blood smears were collected once a week and whenever a volunteer developed symptoms compatible with malaria. The primary endpoint was time to first infection with P. falciparum. Analysis was per protocol. FINDINGS: 250 men (131 in the RTS,S/AS02 group and 119 in the control group) received three doses of vaccine and were followed up for 15 weeks. RTS,S/AS02 was safe and well tolerated. P. falciparum infections occurred significantly earlier in the control group than the RTS,S/AS02 group (Wilcoxon's test p=0.018). Vaccine efficacy, adjusted for confounders, was 34% (95% CI 8.0-53, p=0.014). Protection seemed to wane: estimated efficacy during the first 9 weeks of follow-up was 71% (46-85), but decreased to 0% (-52 to 34) in the last 6 weeks. Vaccination induced strong antibody responses to circumsporozoite protein and strong T-cell responses. Protection was not limited to the NF54 parasite genotype from which the vaccine was derived. 158 men received a fourth dose the next year and were followed up for 9 weeks; during this time, vaccine efficacy was 47% (4-71, p=0.037). INTERPRETATION: RTS,S/AS02 is safe, immunogenic, and is the first pre-erythrocytic vaccine to show significant protection against natural P. falciparum infection.

A phase I safety and immunogenicity trial with the candidate malaria vaccine RTS,S/SBAS2 in semi-immune adults in The Gambia.

RTS,S is a novel pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein (CSP) of Plasmodium falciparum linked to hepatitis B surface antigen (HBs) and combined with a novel adjuvant system (SBAS2). We have conducted a Phase I trial with three doses of this vaccine given at 0, 1, and 6 months to 20 semi-immune, adult, male volunteers in The Gambia to assess its safety and immunogenicity. Eighteen of the 20 volunteers completed the study. There were no clinically significant local or systemic adverse events following each vaccination. Hematologic and biochemical indices before and two weeks after each vaccination showed no evidence of toxicity. Antibody titers to both CSP and HBs showed a significant increase after vaccination; these were the largest after the third dose. We conclude that the RTS,S/SBAS2 vaccine induces no significant toxicity in this semi-immune population and produces significant increases in antibody titers to CSP.

Fourier transform infrared spectroscopy study of the secondary structure of the reconstituted Neurospora crassa plasma membrane H(+)-ATPase and of its membrane-associated proteolytic peptides.

We reconstituted purified plasma membrane H(+)-ATPase from Neurospora crassa into soybean phospholipid vesicles (lipid/ATPase ratio of 5:1 w/w). The proteoliposomes contained an active ATPase, oriented inside-out. They were subjected to proteolysis by using Pronase, proteinase K, trypsin, and carboxypeptidase Y. Fourier transform infrared attenuated total reflection spectroscopy indicates that the amount of protein remaining after hydrolysis and elimination of the extramembrane domain of ATPase represents about 43% of the intact protein. The secondary structure of intact ATPase and of the membrane-associated domain of ATPase was determined by infrared spectroscopy. The membrane domain shows a typical alpha-helix and beta-sheet absorption. Polarized infrared spectroscopy reveals that the orientation of the helices is about perpendicular to the membrane. Amide hydrogen/deuterium exchange kinetics performed for the intact H(+)-ATPase and for the membrane-associated domain demonstrate that this part of ATPase shows less accessibility to the solvent than the entire protein but remains much more accessible to the solvent than bacteriorhodopsin membrane segments.

Reconstitution of the Neurospora crassa plasma membrane H(+)-adenosine triphosphatase.

The purified H(+)-ATPase of the Neurospora crassa plasma membrane has been reconstituted by a gel filtration method into lipidic vesicles using sodium deoxycholate as the detergent. Reconstitution was performed for lipid/ATPase ratios ranging from 1000:1 to 5:1 (w/w). Whatever the lipid/ATPase ratio, the ATPase molecules completely associate with the lipid vesicles. The ATPase specific activity is identical for all proteoliposomes regardless of the lipid/ATPase ratio, but the H+ transport decreases at high protein/lipid ratios, suggesting that the proteoliposomes are more leaky to H+ as the amount of protein inserted into the lipidic membrane increases. Analysis of the fragments generated by trypsin proteolysis in the presence and in the absence of MgATP+ vanadate indicate that most of the reconstituted ATPase molecules are able to assume the transition state of the enzyme dephosphorylation reaction, and are therefore functional. The orientation (inside-out or rightside-out) of the ATPase molecules in the vesicles is independent of the lipid/ATPase ratio chosen for the reconstitution. For all the lipid/ATPase ratios tested, most of the ATPase molecules (> 99%) expose their cytoplasmic side to the outside of the reconstituted proteoliposomes. The size of the vesicles increases parallel to the ATPase amount. Although the H+ leakiness of our preparation at low lipid/protein ratios prevents proton pumping measurements, the reconstitution procedure described here has the main advantage on other procedures to allow the obtention of vesicles at high protein-to-lipid ratios, facilitating further structural characterization of the ATPase by biochemical and biophysical techniques. Therefore, the procedure described here could be of general interest in the field of membrane protein study.

Tertiary conformational changes of the Neurospora crassa plasma membrane H(+)-ATPase monitored by hydrogen/deuterium exchange kinetics. A Fourier transformed infrared spectroscopy approach.

Attenuated total reflection Fourier transform infrared spectroscopy of hydrated films of the Neurospora crassa plasma membrane H(+)-ATPase has been used to monitor the alpha-helix and beta-sheet contents and amide hydrogen exchange rates of the enzyme in the absence of ligands or locked in several stages of the enzyme catalytic cycle by MgADP, Mg-vanadate, and MgATP-vanadate. No difference larger than 2% was found in the alpha-helix or beta-sheet content of the H(+)-ATPase in different conformational states. However, when the rate of hydrogen/deuterium exchange monitored by the evolution of the area of amide II and amide II' is decomposed into three components, the number of amide protons characterized by a short exchange rate (1.1 min) falls from 38% of the protein amide protons (or 37% in the presence of Mg2+ alone) to 24-27% in the presence of Mg-vanadate and MgATP-vanadate and to 19% in the presence of MgADP. These results suggest that the conformational changes known to occur when the H(+)-ATPase interacts with the above ligands are predominantly tertiary structure changes.

Secondary structure of the membrane-bound form of the pore-forming domain of colicin A. An attenuated total-reflection polarized Fourier-transform infrared spectroscopy study.

The structure of the pore-forming domain of the bacterial toxin colicin A was studied by attenuated total-reflection polarized Fourier-transform infrared spectroscopy. This channel-forming fragment interacts with dimyristoylglycerophosphoglycerol (Myr2GroPGro) vesicles and forms disk-like complexes. Analysis of the shape of the amide I' band indicates that its secondary structure is not affected by the pH 5.0-7.2. However, 5-10% of the peptide amino acids adopt an alpha-helical structure upon complex formation with Myr2GroPGro, while the random-coil and beta-sheet structure contents decrease. Interestingly, the increase in alpha-helical content is essentially due to an increase in the high-frequency component of the alpha-helical domain of amide I'. The fact that only this component was 90 degrees polarized (i.e. the helix is parallel to the acyl chain) suggests that only this particular type of helix is associated with the Myr2GroPGro bilayer.

Differences in primary structure among five phospholipases A2 from Heloderma suspectum.

Five increasingly anionic phospholipases A2 (Pa1-Pa5) exist in the venom of the lizard Heloderma suspectum. We recently elucidated the sequence of Pa5, the most abundant and most active variant, towards emulsified phosphatidylcholines. Here we present the primary structures of Pa2, Pa3 (subvariants a and b) and Pa4, based on Edman degradation of tryptic, endoproteinase Arg-C and chymotryptic fragments of the reduced and S-carboxymethylated proteins. Pa1-Pa5, considered collectively, belong to an original class of secretory phospholipases A2 with 141-143 residues, a short hydrophobic N-terminus, 10 half-cystine residues and an extended C-terminus. The only known phospholipase A2 with characteristics close enough to be a member of the same class is that present in the venom from the insect Apis mellifera. More specifically, the sequences of Pa3 and Pa5 are almost identical, and those of Pa2 and Pa4 are also quite similar. Both groups diverge enough to indicate the translation of two mRNA species in the venom gland. The primary structure of Pa3 reveals the existence of subvariants a and b, the sequence of which is identical to that previously defined for Pa5, except that the C-terminal tripeptide GEG in Pa5 is replaced by the dipeptide GE in Pa3a and the tetrapeptide GEGR in Pa3b, Pa4, when compared to Pa5, shows 21 substitutions with a cluster of five modified amino acids in positions 40-44, immediately after the catalytic segment amino acids 30-39, and added changes scattered before the C-terminus. Pa2 differs from Pa4 only by the absence of the Gly142 C-terminal residue. The 15% difference in primary structure observed between the Pa3-Pa5 and Pa2-Pa4 subgroups might be largely responsible for their distinct biological properties.