Scaling Up Family Planning to Reduce Maternal and Child Mortality: The Potential Costs and Benefits of Modern Contraceptive Use in South Africa

Introduction

Family planning contributes significantly to the prevention of maternal and child mortality. However, many women still do not use modern contraception and the numbers of unintended pregnancies, abortions and subsequent deaths are high. In this paper, we estimate the service delivery costs of scaling up modern contraception, and the potential impact on maternal, newborn and child survival in South Africa.

Methods

The Family Planning model in Spectrum was used to project the impact of modern contraception on pregnancies, abortions and births in South Africa (2015-2030). The contraceptive prevalence rate (CPR) was increased annually by 0.68 percentage points. The Lives Saved Tool was used to estimate maternal and child deaths, with coverage of essential maternal and child health interventions increasing by 5% annually. A scenario analysis was done to test impacts when: the change in CPR was 0.1% annually; and intervention coverage increased linearly to 99% in 2030.

Results

If CPR increased by 0.68% annually, the number of pregnancies would reduce from 1.3 million in 2014 to one million in 2030. Unintended pregnancies, abortions and births decrease by approximately 20%. Family planning can avert approximately 7,000 newborn and child and 600 maternal deaths. The total annual costs of providing modern contraception in 2030 are estimated to be US$33 million and the cost per user of modern contraception is US$7 per year. The incremental cost per life year gained is US$40 for children and US$1,000 for mothers.

Conclusion

Maternal and child mortality remain high in South Africa, and scaling up family planning together with optimal maternal, newborn and child care is crucial. A huge impact can be made on maternal and child mortality, with a minimal investment per user of modern contraception.     

Localized egg-cell expression of effector proteins for targeted modification of the Arabidopsis genome

Targeted modification of the genome is an important genetic tool, which can be achieved via homologous, non-homologous or site-specific recombination. Although numerous efforts have been made, such a tool does not exist for routine applications in plants. This work describes a simple and useful method for targeted mutagenesis or gene targeting, tailored to floral-dip transformation in Arabidopsis, by means of specific protein expression in the egg cell. Proteins stably or transiently expressed under the egg apparatus-specific enhancer (EASE) were successfully localized to the area of the egg cell. Moreover, a zinc-finger nuclease expressed under EASE induced targeted mutagenesis. Mutations obtained under EASE control corresponded to genetically independent events that took place specifically in the germline. In addition, RAD54 expression under EASE led to an approximately 10-fold increase in gene targeting efficiency, when compared with wild-type plants. EASE-controlled gene expression provides a method for the precise engineering of the Arabidopsis genome through temporally and spatially controlled protein expression. This system can be implemented as a useful method for basic research in Arabidopsis, as well as in the optimization of tools for targeted genetic modifications in crop plants.     

Postharvest heat and conditioning treatments activate different molecular responses and reduce chilling injuries in grapefruit

A combination of hot water (a rinse at 62 degrees C for 20 s) and conditioning (pre-storage at 16 degrees C for 7 d) treatments synergistically reduced chilling injury development in grapefruit (Citrus paradisi, cv. "Star Ruby") during cold storage at 2 degrees C, suggesting that the treatments may activate different chilling tolerance responses. To study the molecular mechanisms involved, chilling- and conditioning-responsive genes were isolated by polymerase chain reaction (PCR) cDNA subtraction, cDNA libraries were constructed from hot water- and conditioning-treated fruit, and cDNA sequencing was used to identify putative stress-responsive and chilling tolerance genes. PCR cDNA subtraction revealed the identification of 17 chilling-responsive and heat- and conditioning-induced genes, and the expression patterns of 11 additional stress-related genes, antioxidant defensive genes, and genes encoding enzymes involved in membrane lipid modifications were characterized. It was found that hot water and conditioning treatments had little effect on gene expression by themselves, but rather had a priming effect, and enabled the fruit to activate their defence responses after subsequent exposure to chilling. RNA gel blot hybridizations revealed that the expression patterns of eight genes, including HSP19-I, HSP19-II, dehydrin, universal stress protein (USP), EIN2, 1,3;4-beta-D-glucanase, and superoxide dismutase (SOD), were specifically regulated by the heat treatment, and four genes, including fatty acid desaturase2 (FAD2) and lipid transfer protein (LTP), were specifically regulated by the conditioning treatment. Furthermore, four more genes were identified, including a translation initiation factor (SUI1), a chaperonin, and alcohol dehydrogenase (ADH), that were commonly regulated by both heat and conditioning treatments. According to these data, it is suggested that pre-storage heat and conditioning treatments may enhance fruit chilling tolerance by activating different molecular mechanisms. The hot water treatment activates mainly the expression of various stress-related genes, whereas the conditioning treatment activates mainly the expression of lipid membrane modification enzymes.     

A 41 kDa protein isolated from maize mesocotyl cell walls immunolocalizes to plasmodesmata

Summary Plasmodesmata, dynamic pore structures that traverse plant cell walls, function in cytoplasmic transport between contiguous cells. Cell walls containing embedded plasmodesmata were isolated from mesocotyls of etiolated maize seedlings. Proteins associated with the isolated walls were separated by SDS-PAGE and antibodies were generated against a 41 kDa protein, one of several associated with this wall fraction. Immunoblot analysis showed that the 41 kDa polypeptide was also associated with other subcellular fractions obtained following tissue homogenization and differential centrifugation. The wall associated 41 kDa protein is apparently a peripheral membrane protein since it could be extracted by high salt and high pH. Silver-enhanced immunogold light microscopy showed that the 41 kDa protein was associated with the cell walls of cells both in the stele and cortex. The immunolabeling pattern was transwall and punctate. Electron microscopic immuno-gold labeling localized the polypeptide to plasmodesmata and to electron dense cytoplasmic structures that are apparently Golgi membranes. The significance of the presence of this protein in the Golgi is discussed.Abbreviations ER endoplasmic reticulum     

Growth Cycle of Predacious Bdellovibrios in a Host-Free Extract System and Some Properties of the Host Extract

Host-free growth and reproduction of a host-dependent strain of Bdellovibrio bacteriovorus incubated with an extract from host cells were studied. The morphological changes occurring in the cells were correlated with deoxyribonucleic acid (DNA) synthesis as measured by labeled nucleotide or orthophosphate incorporation. The host-free developmental cycle of Bdellovibrio is similar to that of the two-membered system; the early loss of flagella, the elongation into filaments, and multiple fission into flagellated progeny are typical for both host-free and intraperiplasmic development of bdellovibrios. Filament length and time of division appear to depend on the concentration of the host extract. Host extract was found to be heat stable and DNase stable, and Pronase sensitive and RNase sensitive. Addition of ribonucleic acid to the extract medium at various times during the Bdellovibrio growth cycle demonstrated that host extract is required continuously during the cycle for growth. The observations reported give a unified picture of Bdellovibrio development and allow for the suggestion that wild-type bdellovibrios depend upon the presence of some host factor for induction of DNA synthesis, whereas depletion of host factor triggers division. The ecological implications of such host dependence are discussed.     

Lifestyle Behaviors in Metabolically Healthy and Unhealthy Overweight and Obese Women: A Preliminary Study

Background

Few studies have examined dietary data or objective measures of physical activity (PA) and sedentary behavior among metabolically healthy overweight/obese (MHO) and metabolically unhealthy overweight/obese (MUO). Thus, the purpose is to determine whether PA, sedentary behavior and/or diet differ between MHO and MUO in a sample of young women.

Methods

Forty-six overweight/obese (BMI ≥25 kg/m²) African American and Caucasian women 19–35 years were classified by cardiometabolic risk factors, including elevated blood pressure, triglyceride, glucose and C-reactive protein, low high density lipoprotein, and insulin resistance (MUO ≥2; MHO, <2). Time (mins/day) in light, moderate, vigorous PA, and sedentary behavior were estimated using an accelerometer (≥3 days; ≥8 hrs wear time). Questionnaires were used to quantify sitting time, TV/computer use and usual daily activity. The Block Food Frequency Questionnaire assessed dietary food intake. Differences between MHO and MUO for lifestyle behaviors were tested with linear regression (continuous data) or logistic regression (categorical data) after adjusting for age, race, BMI, smoking and accelerometer wear and/or total kilocalories, as appropriate.

Results

Women were 26.7±4.7 years, with a mean BMI of 31.1±3.7 kg/m², and 61% were African American. Compared to MUO (n = 9), MHO (n = 37; 80%) spent less mins/day in sedentary behavior (difference: -58.1±25.5, p = 0.02), more mins/day in light PA (difference: 38.2±16.1, p = 0.02), and had higher daily METs (difference: 0.21±0.09, p = 0.03). MHO had higher fiber intakes (g/day of total fiber, soluble fiber, fruit/vegetable fiber, bean fiber) and daily servings of vegetables; but lower daily dairy servings, saturated fat, monounsaturated fat and trans fats (g/day) compared to MUO.

Conclusion

Compared to MUO, MHO young women demonstrate healthier lifestyle habits with less sedentary behavior, more time in light PA, and healthier dietary quality for fat type and fiber. Future studies are needed to replicate findings with larger samples that include men and women of diverse race/ethnic groups.     

Differential phosphoprotein labeling (DIPPL), a method for comparing live cell phosphoproteomes using simultaneous analysis of (33)P- and (32)P-labeled proteins

We developed a differential method to reveal kinase-specific phosphorylation events in live cells. In this method, cells in which the specified kinase is inactive are labeled with (32)Pi, whereas cells in which the kinase is active are labeled with (33)Pi. The two cell extracts are then mixed, and proteins are separated on a single two-dimensional gel. The dried gel is exposed twice. The first exposure reveals both (32)P- and (33)P-labeled proteins; the kinase-specific spots are revealed because of (33)P labeling. The second exposure is conducted with two acetate sheets intervening between the gel and the detection plate. This maneuver screens out the less energetic (33)P-labeled proteins while allowing the more energetic (32)P-labeled proteins to be detected, thus leaving only those spots that were phosphorylated independently of the specified kinase. We demonstrate the utility of this method for detecting kinase substrates in rare tissue by focusing on extracellular signal-regulated kinase-specific phosphorylation of stathmin/OP18 in primary rat sympathetic neurons.     

Nitric oxide-induced cell death of cerebrocortical murine astrocytes is mediated through p53- and Bax-dependent pathways

We have investigated the mechanism by which nitric oxide (NO) induces the death of mouse astrocytes. We show that NO (from donor diethylenetriamine-NO adduct) induces death with several features of apoptosis, including chromatin condensation, phosphatidylserine exposure on the outer leaflet of the plasma membrane, Bax translocation to the mitochondria and cytochrome c release, but no caspase activation or nuclear fragmentation is observed. Nitric oxide also elevates p53 expression, causing a concomitant increase in p53 serine 18 phosphorylation and p53 translocation from the cytoplasm to the nucleus. Activation of Bax and p53 is important for NO-induced apoptosis-like cell death because Bax- or p53-deficient astrocytes are much more resistant than wild-type cells to the same NO treatment. We further demonstrate that LY294002-sensitive kinases are responsible for controlling serine 18 phosphorylation of p53, thereby regulating the pro-apoptotic activity of p53 in astrocytes. While apoptosis is suppressed in the presence of LY294002, however, death by necrosis is increased, suggesting that LY294002-sensitive kinases additionally suppress a latent necrotic response to NO. We conclude that NO-induced death in astrocytes is mediated by p53- and Bax-dependent mechanisms, although full manifestation of apoptosis is aborted by concomitant inhibition of caspase activation. More generally, our data suggest that apoptotic mediators should be evaluated as the cause of cell death even in cases where a full apoptotic phenotype is lacking.     

Venom effects on monoaminergic systems

The monoamines, dopamine, epinephrine, histamine, norepinephrine, octopamine, serotonin and tyramine serve many functions in animals. Many different venoms have evolved to manipulate monoaminergic systems via a variety of cellular mechanisms, for both offensive and defensive purposes. One common function of monoamines present in venoms is to produce pain. Some monoamines in venoms cause immobilizing hyperexcitation which precedes venom-induced paralysis or hypokinesia. A common function of venom components that affect monoaminergic systems is to facilitate distribution of other venom components by causing vasodilation at the site of injection or by increasing heart rate. Venoms of some scorpions, spiders, fish and jellyfish contain adrenergic agonists or cause massive release of catecholamines with serious effects on the cardiovascular system, including increased heart rate. Other venom components act as agonists, antagonists or modulators at monoaminergic receptors, or affect release, reuptake or synthesis of monoamines. Most arthropod venoms have insect targets, yet, little attention has been paid to possible effects of these venoms on monoaminergic systems in insects. Further research into this area may reveal novel effects of venom components on monoaminergic systems at the cellular, systems and behavioral levels.