Impact of fetal growth restriction on pregnancy outcome in women undergoing expectant management for preterm pre-eclampsia.

OBJECTIVES: To assess whether coexisting fetal growth restriction (FGR) influences pregnancy latency among women with preterm pre-eclampsia undergoing expectant management. Secondary outcomes assessed were indication for delivery, mode of delivery and rate of serious adverse maternal and perinatal outcomes. METHODS: We conducted a secondary analysis of the Pre-eclampsia Intervention (PIE) and the Pre-eclampsia Intervention 2 (PI2) trial data. These randomized controlled trials evaluated whether esomeprazole and metformin could prolong gestation of women diagnosed with pre-eclampsia between 26 and 32 weeks of gestation undergoing expectant management. Delivery indications were deteriorating maternal or fetal status, or reaching 34 weeks' gestation. FGR (defined by Delphi consensus) at the time of pre-eclampsia diagnosis was examined as a predictor of outcome. Only placebo data from PI2 were included, as the trial showed that metformin use was associated with prolonged gestation. All outcome data were collected prospectively from diagnosis of pre-eclampsia to 6 weeks after the expected due date. RESULTS: Of the 202 women included, 92 (45.5%) had FGR at the time of pre-eclampsia diagnosis. Median pregnancy latency was 6.8 days in the FGR group and 15.3 days in the control group (difference 8.5 days; adjusted 0.49-fold change (95% CI, 0.33-0.74); P < 0.001). FGR pregnancies were less likely to reach 34 weeks' gestation (12.0% vs 30.9%; adjusted relative risk (aRR), 0.44 (95% CI, 0.23-0.83)) and more likely to be delivered for suspected fetal compromise (64.1% vs 36.4%; aRR, 1.84 (95% CI, 1.36-2.47)). More women with FGR underwent a prelabor emergency Cesarean section (66.3% vs 43.6%; aRR, 1.56 (95% CI, 1.20-2.03)) and were less likely to have a successful induction of labor (4.3% vs 14.5%; aRR, 0.32 (95% CI, 0.10-1.00)), compared to those without FGR. The rate of maternal complications did not differ significantly between the two groups. FGR was associated with a higher rate of infant death (14.1% vs 4.5%; aRR, 3.26 (95% CI, 1.08-9.81)) and need for intubation and mechanical ventilation (15.2% vs 5.5%; aRR, 2.97 (95% CI, 1.11-7.90)). CONCLUSION: FGR is commonly present in women with early preterm pre-eclampsia and outcome is poorer. FGR is associated with shorter pregnancy latency, more emergency Cesarean deliveries, fewer successful inductions and increased rates of neonatal morbidity and mortality. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Delivery outcomes in women with morbid obesity, where induction of labour was planned to prevent post-term complications.

Morbid obesity and prolonged pregnancy are independently associated with adverse delivery and perinatal outcomes. We conducted a retrospective observational study on otherwise uncomplicated women with a body mass index (BMI) ≥ 40 kg/m2 where, having reached term, induction of labour (IOL) was planned, to prevent prolonged pregnancy. The primary aim was to describe delivery outcomes and short-term maternal and perinatal adverse events. Of 117 cases included, 69 (59%) laboured spontaneously before the induction date, while 48 (41%) required an IOL. Of 48 patients that underwent an IOL, 22 (45.8%) achieved vaginal delivery, compared to 55 (79.7%) who laboured spontaneously (p = <.001). Twenty-two (18.8%) of the 117 babies weighed more than 4000 g, with 13 of these delivered vaginally. Overall, term patients with morbid obesity who laboured spontaneously before requiring induction, had a high rate of vaginal delivery. However, when IOL was required, the rate of caesarean delivery rose dramatically.Impact statementWhat is already known on this subject? Morbid obesity and prolonged pregnancy are independently associated with adverse delivery and perinatal outcomes. Induction of labour (IOL) increases the workload in busy units.What do the results of this study add? These results help inform accurate counselling on delivery outcomes, which is integral to respectful care, for the continuously increasing numbers of morbidly obese pregnant women.What the implications are of these findings for clinical practice and/or further research? It is preferable to avoid semi- or urgent caesarean deliveries in morbidly obese women after IOL. The outcomes of earlier induction of labour from 39- or 40-weeks' gestation requires investigation. Earlier induction may reduce the numbers of caesarean deliveries for abnormal cardiotocograph during the process.

A comparison between point-of-care testing and venous glucose determination for the diagnosis of diabetes mellitus 6-12 weeks after gestational diabetes.

AIM: To evaluate point-of-care-testing (POCT) for the diagnosis of Type 2 diabetes mellitus 6-12 weeks post-partum in women with gestational diabetes (GDM). METHODS: Post-partum glucose assessment (75-mg oral glucose tolerance test, OGTT) was performed prospectively in 122 women with GDM (1 November 2015 to 1 November 2017) at Tygerberg Hospital, Cape Town, South Africa. Individuals with known pre-existing diabetes were excluded. The accuracy and clinical utility of POCT (capillary finger-prick) were compared with laboratory plasma glucose (hexokinase and glucokinase methods). The OGTT consisted of two time points (fasting and 2 h) during which concurrent glucose samples (POCT and laboratory) were obtained. Bland-Altman plots and paired analysis were used to assess the analytical accuracy of POCT, whereas its diagnostic performance was determined using positive and negative predictive values to calculate specificity and sensitivity. RESULTS: Spearman's ranked correlation analysis indicated a strong association between POCT and laboratory glucose values at both OGTT time points (fasting, r = 0.95, P < 0.0001; 2 h, r = 0.88, P < 0.0001). Thirty-six women were diagnosed with Type 2 diabetes based on gold standard laboratory glucose levels (fasting > 7 mmol/l; 2 h > 11.1 mmol/l). POCT correctly identified Type 2 diabetes in 78% of women (28 of 36) with a positive predictive value of 89.3% and a negative predictive value of 96.7% at the fasting time point. The sensitivity and specificity of POCT to diagnose Type 2 diabetes were 89% (fasting), 85.7% (2 h) and 96.7% (fasting), 98.5% (2 h) respectively. POCT proved less sensitive to diagnose pre-diabetes (69%) but displayed satisfactory specificity (92%) at both time points assessed. CONCLUSION: POCT accurately identifies women with Type 2 diabetes 6-12 weeks after GDM.

Shoo fly, don't bother me! Efficacy of traditional methods of protecting cattle from tsetse.

Studies were made of the efficacy of using smoke and housing to protect cattle from tsetse (Diptera: Glossinidae) in Zimbabwe. The efficacy of smoke was assessed by its effect on catches in Epsilon traps baited with a blend of acetone, 1-octen-3-ol, 4-methylphenol and 3-n-propylphenol. The efficacies of different types of kraal (enclosure) were gauged according to the catches of electrocuting targets (E-targets), baited with natural ox odour, placed within various designs of kraal. Smoke from burning wood (Colophospermum mopane) or dried cow dung reduced the catch of traps by approximately 50-90%. Kraals with a continuous wooden or netting wall, 1.5 m high, reduced catches of E-targets by approximately 75%. Arrangements of electric nets were used to assess the numbers of tsetse attacking live cattle within kraals and/or near sources of smoke. The results confirmed findings with traps and E-targets: kraals reduced the numbers of tsetse that fed by approximately 80% and smoke reduced the numbers attracted by approximately 70%; the use of both reduced overall attack rates by approximately 90%. The inclusion of 4-methylguaiacol, a known repellent for tsetse and a natural component of wood smoke, halved the catches of traps and E-targets and the numbers of tsetse attacking cattle. The practical benefits and difficulties of using repellents and/or housing to manage trypanosomiases are discussed.

The impact of an obstetrician-led, labor ward critical care unit: A prospective comparison of outcomes before and after establishment.

OBJECTIVE: To investigate the outcomes of critically ill obstetric patients managed in a obstetric critical care unit in South Africa. METHODS: Patients with severe maternal morbidity managed in the labor ward of Tygerberg Hospital were studied over three months before the establishment of the obstetrician-led obstetric critical care unit. One year later, patients managed in the obstetric critical care unit were studied using the same methods. The primary outcome measures were maternal morbidity and mortality. RESULTS: In the before-obstetric critical care unit prospective audit 63 patients met criteria for obstetric critical care. During the second period 60 patients were admitted to the obstetric critical care unit. There were no significant differences between the groups in baseline characteristics, admission indications or Acute Physiology and Chronic Health Evaluation scores. Continuous positive airway pressure (p < 0.01) was utilized more in the second group. Seven deaths occurred in the first, but none in the second group (p = 0.01). CONCLUSION: The establishment of an obstetrician-led obstetric critical care unit facilitated a decrease in maternal mortality.Trial registration: Not applicable.

Effect of progesterone on cervical shortening in women at risk for preterm birth: secondary analysis from a multinational, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: To determine whether progesterone supplementation alters cervical shortening in women at increased risk for preterm birth. METHODS: We performed a planned secondary analysis from a large, multinational preterm birth prevention trial of daily intravaginal progesterone gel, 90 mg, compared with placebo in women with a history of spontaneous preterm birth or premature cervical shortening. Transvaginal cervical length measurements were obtained in all randomized patients at baseline (18 + 0 to 22 + 6 weeks' gestation) and at 28 weeks' gestation. For this secondary analysis, the difference in cervical length between these time points was compared for the study population with a history of spontaneous preterm birth and for a population with premature cervical shortening (< or = 30 mm) at randomization. Differences between groups in cervical length for the 28-week examination were analyzed using ANCOVA, including adjustment for relevant clinical parameters and maternal characteristics. RESULTS: Data were analyzed from 547 randomized patients with a history of preterm birth. The progesterone-treated patients had significantly less cervical shortening than the placebo group (difference 1.6 (95% CI, 0.3-3.0) mm; P = 0.02, ANCOVA). In the population of 104 subjects with premature cervical shortening at randomization, the cervical length also differed significantly on multivariable analysis, with the treatment group preserving more cervical length than the placebo group (difference 3.3 (95% CI, 0.3-6.2) mm; P = 0.03, ANCOVA), with adjustment for differences in cervical length at screening. A significant difference was also observed between groups for categorical outcomes including the frequency of cervical length progression to < or = 25 mm and a > or = 50% reduction in cervical length from baseline in this subpopulation. CONCLUSIONS: Intravaginal progesterone enhances preservation of cervical length in women at high risk for preterm birth.

Avoiding paternalism but not moral perplexity.

Maternal autonomy has replaced medical paternalism, but conflicts between beneficence and autonomy persist.

Correction of beam errors in high power laser diode bars and stacks.

The beam errors of an 11 bar laser diode stack fitted with fast-axis collimator lenses have been corrected by a single refractive plate, produced by laser cutting and polishing. The so-called smile effect is virtually eliminated and collimator aberration greatly reduced, improving the fast-axis beam quality of each bar by a factor of up to 5. The single corrector plate for the whole stack ensures that the radiation from all the laser emitters is parallel to a common axis. Beam-pointing errors of the bars have been reduced to below 0.7 mrad.

RadA protein from Archaeoglobus fulgidus forms rings, nucleoprotein filaments and catalyses homologous recombination.

Proteins that catalyse homologous recombination have been identified in all living organisms and are essential for the repair of damaged DNA as well as for the generation of genetic diversity. In bacteria homologous recombination is performed by the RecA protein, whereas in the eukarya a related protein called Rad51 is required to catalyse recombination and repair. More recently, archaeal homologues of RecA/Rad51 (RadA) have been identified and isolated. In this work we have cloned and purified the RadA protein from the hyperthermophilic, sulphate-reducing archaeon Archaeoglobus fulgidus and characterised its in vitro activities. We show that (i) RadA protein forms ring structures in solution and binds single- but not double-stranded DNA to form nucleoprotein filaments, (ii) RadA is a single-stranded DNA-dependent ATPase at elevated temperatures, and (iii) RadA catalyses efficient D-loop formation and strand exchange at temperatures of 60-70 degrees C. Finally, we have used electron microscopy to visualise RadA-mediated joint molecules, the intermediates of homologous recombination. Intriguingly, RadA shares properties of both the bacterial RecA and eukaryotic Rad51 recombinases.

Postmenopausal hormone therapy and quality of life.

OBJECTIVE: To evaluate whether hormonal therapy (HT) had any significant effect on quality of life (QoL) in a selected group of postmenopausal women. METHODS: The study was conducted in a specialist private practice in Tygerberg, Cape Town, South Africa, over an 18-month period ending in July 2003. A questionnaire using the Utian Quality of Life (UQoL) scale was posted to all women with established postmenopausal status, seen over this period. 541 questionnaires were posted, 421 returned and 398 could be used. Women gave written informed consent. RESULTS: The average age of the women was 60 years. 313 women (78.6%) were using hormone therapy (HT) while 275 women (69.1%) reported concomitant medical problems. HT users had significantly higher scores in three of the four QoL domains, namely, occupational (p=0.046), emotional (p=0.03), and sexual (p=0.009). There was no significant difference in the health domain (p=0.2). CONCLUSION: This study found that post-menopausal South African women experienced that HT had a positive effect on global quality of life.

The attitudes of two groups of South African women towards mode of delivery.

OBJECTIVE: To determine whether 2 specific groups of women prefer vaginal or abdominal delivery. METHODS: Forty-six black and 54 colored (of mixed race, the predominant population group) primigravidas and 59 black and 62 colored multigravidas were interviewed between April 2003 and February 2004 at Tygerberg Hospital, Tygerberg, South Africa. RESULTS: Among primigravidas, 89% of black women and 83% of colored women preferred vaginal delivery. Among the multigravidas, 86% of black women and 79% of colored women preferred vaginal delivery. Most women believed that they would recover more quickly (65%) and with less pain (32%) after vaginal delivery. Forty-one percent of all women viewed episiotomy as the greatest disadvantage of vaginal delivery, while 43% were unaware of any advantage to cesarean delivery. CONCLUSION: Most colored and black women preferred vaginal over cesarean delivery. A challenge to healthcare personnel is to educate women about both routes.

The crystal structure of Escherichia coli class II fructose-1, 6-bisphosphate aldolase in complex with phosphoglycolohydroxamate reveals details of mechanism and specificity.

The structure of a class II fructose-1,6-bisphosphate aldolase in complex with the substrate analogue and inhibitor phosphoglycolohydroxamate (PGH) has been determined using X-ray diffraction terms to a resolution of 2.0 A (1 A=0.1 nm). The crystals are trigonal, space group P3121 with a=b=78.24 A, c=289.69 A. The asymmetric unit is a homodimer of (alpha/beta)8 barrels and the model has refined to give R-work 19.2 %, R-free (based on 5 % of the data) 23.0 %. PGH resembles the ene-diolate transition state of the physiological substrate dihydroxyacetone phosphate. It is well ordered and bound in a deep polar cavity at the C-terminal end of the (alpha/beta)8 barrel, where it chelates the catalytic zinc ion using hydroxyl and enolate oxygen atoms. Trigonal bipyramidal coordination of the zinc ion is completed by three histidine residues. The complex network of hydrogen bonds at the catalytic centre is required to organise the position of key functional groups and metal ion ligands. A well-defined monovalent cation-binding site is observed following significant re-organisation of loop structures. This assists the formation of a phosphate-binding site on one side of the barrel that tethers PGH in the catalytic site. The positions of functional groups of substrate and putative interactions with key amino acid residues are identified. Knowledge of the complex structure complements the results of spectroscopic and site-directed mutagenesis studies, and contributes to our understanding of the mechanism and substrate specificity of this family of enzymes. A reaction mechanism distinct from that proposed for other class II aldolases is discussed. The results suggest that the class II aldolases should be sub-divided into two groups on the basis of both distinct folds and mechanism.

The three-dimensional structure of a Plasmodium falciparum cyclophilin in complex with the potent anti-malarial cyclosporin A.

Cyclosporin A (CsA) is a potent anti-malarial compound in vitro and in vivo in mice though better known for its immunosuppressive properties in humans. Crystal structures of wild-type and a double mutant Plasmodium falciparum cyclophilin (PfCyP19 and mPfCyP19) complexed with CsA have been determined using diffraction terms to a resolution of 2.1 A (1 A=0.1 nm). The wild-type has a single PfCyP19/CsA complex per asymmetric unit in space group P1 and refined to an R-work of 0.15 and R-free of 0.19. An altered cyclophilin, with two accidental mutations, Phe120 to Leu in the CsA binding pocket and Leu171 to Trp at the C terminus, presents two complexes per asymmetric unit in the orthorhombic space group P2(1)2(1)2. This refined to an R-work of 0.18 and R-free 0.21. The mutations were identified from the crystallographic analysis and the C-terminal alteration helps to explain the different crystal forms obtained. PfCyP19 shares approximately 61 % sequence identity with human cyclophilin A (hCyPA) and the structures are similar, consisting of an eight-stranded antiparallel beta-barrel core capped by two alpha-helices. The fold creates a hydrophobic active-site, the floor of which is formed by side-chains of residues from four antiparallel beta-strands and the walls from loops and turns. We identified C-H.O hydrogen bonds between the drug and protein that may be an important feature of cyclophilins and suggest a general mode of interaction between hydrophobic molecules. Comparisons with cyclophilin-dipeptide complexes suggests that a specific C-H.O hydrogen bonding interaction may contribute to ligand binding. Residues Ser106, His99 and Asp130, located close to the active site and conserved in most cyclophilins, are arranged in a manner reminiscent of a serine protease catalytic triad. A Ser106Ala mutant was engineered to test the hypothesis that this triad contributes to CyP function. Mutant and wild-type enzymes were found to have similar catalytic properties.

The effect of calcium supplementation on blood pressure in non-pregnant women with previous pre-eclampsia: An exploratory, randomized placebo controlled study.

BACKGROUND: Epidemiological findings suggest that the link between poverty and pre-eclampsia might be dietary calcium deficiency. Calcium supplementation has been associated with a modest reduction in pre-eclampsia, and also in blood pressure (BP). METHODS: This exploratory sub-study of the WHO Calcium and Pre-eclampsia (CAP) trial aims to determine the effect of 500mg/day elemental calcium on the blood pressure of non-pregnant women with previous pre-eclampsia. Non-pregnant women with at least one subsequent follow-up trial visit at approximately 12 or 24weeks after randomization were included. RESULTS: Of 836 women randomized by 9 September 2014, 1st visit data were available in 367 women of whom 217 had previously had severe pre-eclampsia, 2nd visit data were available in 201 women. There was an overall trend to reduced BP in the calcium supplementation group (1-2.5mmHg) although differences were small and not statistically significant. In the subgroup with previous severe pre-eclampsia, the mean diastolic BP change in the calcium group (-2.6mmHg) was statistically larger than in the placebo group (+0.8mmHg), (mean difference -3.4, 95% CI -0.4 to -6.4; p=0.025). The effect of calcium on diastolic BP at 12weeks was greater than in those with non-severe pre-eclampsia (p=0.020, ANOVA analysis). CONCLUSIONS: There is an overall trend to reduced BP but only statistically significant in the diastolic BP of women with previous severe pre-eclampsia. This is consistent with our hypothesis that this group is more sensitive to calcium supplementation, however results need to be interpreted with caution.

Identification of methyl salicylate as the principal volatile component in the methanol extract of root bark of Securidaca longepedunculata Fers.

Securidaca longepedunculata Fers (Polygalaceae) is commonly used as a medicine in many parts of Africa and shows promise for protecting stored grain against insect pests. Analysis of a methanol extract of the root bark by gas chromatography linked to mass spectrometry (GC/MS) showed a major component accounting for over 90% of the volatile material. This was identified as methyl 2-hydroxybenzoate (methyl salicylate) by comparison of the GC retention times and mass spectrum with those of synthetic standards. This conflicts with an earlier report that the major component is methyl 4-hydroxybenzoate. Two minor components had mass spectra characteristic of 2-hydroxybenzoate esters and were identified as methyl 2-hydroxy-6-methoxybenzoate and its benzyl analogue, again conflicting with an earlier report.

Stabilizing effect of sucrose against irreversible denaturation of rabbit muscle lactate dehydrogenase.

Measurements of the kinetics of activity loss by rabbit muscle lactate dehydrogenase in acetate-chloride buffer, pH 5.0, I 0.20, have shown that the enzyme exhibits greater stability against irreversible inactivation when the buffer is supplemented with sucrose (0.1 M-0.5 M). On the basis of sedimentation equilibrium distributions obtained for enzyme in the absence and presence of sucrose (0.5 M), the lactate dehydrogenase is essentially dimeric in both environments. The observed stabilization of enzyme activity has therefore been considered in terms of the space-filling effects of sucrose on an isomerization equilibrium between native and unfolded forms of dimeric lactate dehydrogenase, which precedes irreversible inactivation of the unfolded isomer. Interpretation of the kinetic results on that basis has led to the conclusion that the initial stage of enzyme unfolding entails a minor change in volume and/or asymmetry of the lactate dehydrogenase that gives rise to a 4% increase in the second virial coefficient describing excluded volume interactions between dimeric enzyme and sucrose.

Interpretation of thermodynamic non-ideality in sedimentation equilibrium experiments on proteins.

This investigation re-examines theoretical aspects of the allowance for effects of thermodynamic non-ideality on the sedimentation equilibrium distribution for a single macromolecular solute, and thereby resolves the question of the constraints that pertain to the definition of the activity coefficient term in the basic sedimentation equilibrium expression. Sedimentation equilibrium results for ovalbumin are then presented to illustrate a simple procedure for evaluating the net charge (valence) of a protein from the magnitude of the second virial coefficient in situations where the effective radius of the protein can be assigned. Finally, published sedimentation equilibrium results on lysozyme are reanalysed to demonstrate the feasibility of employing the dependence of the second virial coefficient upon ionic strength to evaluate both the valence and the effective radius of the non-interacting solute.

Reassessment of the calibration constant for the IAsys biosensor.

A magnitude of 50 are s ng-1 mm2 has been determined for the calibration constant relating biosensor response to the amount of protein bound to the sensor surface of an IAsys cuvette. These studies entailed enzymatic assessment of the extent of lactate dehydrogenase depletion in the liquid phase arising from enzyme binding to a carboxymethyldextran-coated sensor surface, and also estimation of a maximum biosensor response for the electrostatic interaction of ovalbumin with an aminosilane-coated sensor surface. The latter results required correction for contributions to biosensor response resulting from changes in the refractive index of the liquid phase effected by high protein concentrations.

Attraction of Glossina longipalpis (Diptera: Glossinidae) in Guinea-Bissau to odor-baited biconical traps.

The catches of tsetse flies, Stomoxys, and tabanids in biconial traps baited with different synthetic odors were compared in the Jopá-Cobiana Forest, northwestern Guinea-Bissau. Thirty-six traps, the baits of which were randomly interchanged each of 10 sampling days, were baited either with (a) 1-octen-3-ol (octenol) + phenols [4-methylphenol + 3-propylphenol] + acetone + N'dama cow urine ("urine"), (b) octenol + phenols + acetone, (c) octenol + phenols, (d) acetone, (e) acetone + urine, or (f) urine. Six of the traps were not baited (controls). A total of 3,172 tsetse flies (96% Glossina longipalpis Widemann, 3% G. morsitans submorsitans Newstead, and 1% G. palpalis gambiensis Vanderplank), 286 Stomoxys, and 571 Tabanidae was captured. G. longipalpis was caught in statistically greater numbers in traps baited with octenol + phenols + acetone. Traps baited with octenol + phenols, with or without acetone, caught the greatest numbers of tabanids. N'dama urine did not increase the catch of G. longipalpis. Stomoxys was not significantly attracted to any of the odors.

Expectant management of severe pre-eclampsia in the mid-trimester.

OBJECTIVE: To determine maternal and perinatal outcomes with expectant management of severe pre-eclampsia in the mid-trimester, using a defined entry point. DESIGN: Prospective case series. Thirty-nine women admitted from 24 to 27 week's gestation with severe pre-eclampsia, whose pregnancies were otherwise stable, were managed expectantly with careful clinical and biochemical monitoring of maternal and foetal status, together with careful blood pressure control, in a high-care obstetric ward. The aim was to safely prolong the pregnancies and thereby improve perinatal outcome. RESULTS: Gestation was prolonged by a median of 12 (range 3--47) days, with greater periods gained at earlier gestations. The overall perinatal loss was 26% and the neonatal loss 17%. The rates of significant maternal complications were low. CONCLUSION: Expectant management of selected women with severe pre-eclampsia from 24 to 27 weeks' gestation in a tertiary care unit is acceptably safe and improves perinatal outcome.