Maternal Malaria and Malnutrition (M3) initiative, a pooled birth cohort of 13 pregnancy studies in Africa and the Western Pacific.

PURPOSE: The Maternal Malaria and Malnutrition (M3) initiative has pooled together 13 studies with the hope of improving understanding of malaria-nutrition interactions during pregnancy and to foster collaboration between nutritionists and malariologists. PARTICIPANTS: Data were pooled on 14 635 singleton, live birth pregnancies from women who had participated in 1 of 13 pregnancy studies. The 13 studies cover 8 countries in Africa and Papua New Guinea in the Western Pacific conducted from 1996 to 2015. FINDINGS TO DATE: Data are available at the time of antenatal enrolment of women into their respective parent study and at delivery. The data set comprises essential data such as malaria infection status, anthropometric assessments of maternal nutritional status, presence of anaemia and birth weight, as well as additional variables such gestational age at delivery for a subset of women. Participating studies are described in detail with regard to setting and primary outcome measures, and summarised data are available from each contributing cohort. FUTURE PLANS: This pooled birth cohort is the largest pregnancy data set to date to permit a more definite evaluation of the impact of plausible interactions between poor nutritional status and malaria infection in pregnant women on fetal growth and gestational length. Given the current comparative lack of large pregnancy cohorts in malaria-endemic settings, compilation of suitable pregnancy cohorts is likely to provide adequate statistical power to assess malaria-nutrition interactions, and could point towards settings where such interactions are most relevant. The M3 cohort may thus help to identify pregnant women at high risk of adverse outcomes who may benefit from tailored intensive antenatal care including nutritional supplements and alternative or intensified malaria prevention regimens, and the settings in which these interventions would be most effective

Malaria, malnutrition, and birthweight: A meta-analysis using individual participant data.

BACKGROUND: Four studies previously indicated that the effect of malaria infection during pregnancy on the risk of low birthweight (LBW; <2,500 g) may depend upon maternal nutritional status. We investigated this dependence further using a large, diverse study population. METHODS AND FINDINGS: We evaluated the interaction between maternal malaria infection and maternal anthropometric status on the risk of LBW using pooled data from 14,633 pregnancies from 13 studies (6 cohort studies and 7 randomized controlled trials) conducted in Africa and the Western Pacific from 1996-2015. Studies were identified by the Maternal Malaria and Malnutrition (M3) initiative using a convenience sampling approach and were eligible for pooling given adequate ethical approval and availability of essential variables. Study-specific adjusted effect estimates were calculated using inverse probability of treatment-weighted linear and log-binomial regression models and pooled using a random-effects model. The adjusted risk of delivering a baby with LBW was 8.8% among women with malaria infection at antenatal enrollment compared to 7.7% among uninfected women (adjusted risk ratio [aRR] 1.14 [95% confidence interval (CI): 0.91, 1.42]; N = 13,613), 10.5% among women with malaria infection at delivery compared to 7.9% among uninfected women (aRR 1.32 [95% CI: 1.08, 1.62]; N = 11,826), and 15.3% among women with low mid-upper arm circumference (MUAC <23 cm) at enrollment compared to 9.5% among women with MUAC ≥ 23 cm (aRR 1.60 [95% CI: 1.36, 1.87]; N = 9,008). The risk of delivering a baby with LBW was 17.8% among women with both malaria infection and low MUAC at enrollment compared to 8.4% among uninfected women with MUAC ≥ 23 cm (joint aRR 2.13 [95% CI: 1.21, 3.73]; N = 8,152). There was no evidence of synergism (i.e., excess risk due to interaction) between malaria infection and MUAC on the multiplicative (p = 0.5) or additive scale (p = 0.9). Results were similar using body mass index (BMI) as an anthropometric indicator of nutritional status. Meta-regression results indicated that there may be multiplicative interaction between malaria infection at enrollment and low MUAC within studies conducted in Africa; however, this finding was not consistent on the additive scale, when accounting for multiple comparisons, or when using other definitions of malaria and malnutrition. The major limitations of the study included availability of only 2 cross-sectional measurements of malaria and the limited availability of ultrasound-based pregnancy dating to assess impacts on preterm birth and fetal growth in all studies. CONCLUSIONS: Pregnant women with malnutrition and malaria infection are at increased risk of LBW compared to women with only 1 risk factor or none, but malaria and malnutrition do not act synergistically

Control of HCO\u3csub\u3e3\u3c/sub\u3e-Dependent Exchangers by Cyclic Nucleotides in Vascular Smooth Muscle Cells

A variety of membrane transport systems responsible for the regulation of intracellular pH (pHi) have been identified in smooth muscle (Aickin, 1986; Aalkjaer and Cragoe, 1988; Wray, 1988; Kikeri et al., 1990) and smooth muscle-like cells (Boyarsky et al.,1988a,b; Putnam,1990). These include the ubiquitous Na/H exchanger and at least two HC03-dependent transport systems (Fig. 1): i) a putative alkalinizing (Na + HCO3)/C1 exchanger (although the role of Cl in this exchanger is still at issue) (Aickin and Brading, 1984; Aalkjaer and Mulvany, 1988); and ii) an acidifying Cl/HCO3 exchanger. While these exchangers are important for determining steady state pHi (Aalkjaer and Cragoe, 1988; Boyarsky et al., 1988a; Wray, 1988; Kikeri et al., 1990; Putnam and Grubbs, 1990), defending pHiagainst acid/base disturbances (Aalkjaer and Cragoe, 1988; Boyarsky et al., 1988b; Putnam, 1990) and mediating cellular responses to external signals (Berk et al., 1987; Ganz et al., 1989), only the Na/H exchanger has been extensively studied in regard to the factors which regulate its activity. In fact, the regulation of the HCO3-dependent transport systems is poorly studied in any cell

Cell-Type Specific Organization of Glycine Receptor Clusters in the Mammalian Spinal Cord

Glycinergic synapses play a major role in shaping the activity of spinal cord neurons. The spatial organization of postsynaptic receptors is likely to determine many functional parameters at these synapses and is probably related to the integrative capabilities of different neurons. In the present study, we have investigated the organization of gephyrin expression along the dendritic membranes of α- and γ-motoneurons, Ia inhibitory interneurons, and Renshaw cells. Gephyrin is a protein responsible for the postsynaptic clustering of glycine receptors, and the features of gephyrin and glycine receptor α1-subunit immunofluorescent clusters displayed similar characteristics on ventral horn spinal neurons. However, the density of clusters and their topographical organization and architecture varied widely in different neurons and in different dendritic regions. For motoneurons and Ia inhibitory interneurons, cluster size and complexity increased with distance from the soma, perhaps as a mechanism to enhance the influence of distal synapses. Renshaw cells were special in that they displayed an abundant complement of large and morphologically complex clusters concentrated in their somas and proximal dendrites. Serial electron microscopy confirmed that the various immunoreactivity patterns observed with immunofluorescence accurately parallel the variable organization of pre- and postsynaptic active zones of glycinergic synapses. Finally, synaptic boutons from single-labeled axons of glycinergic neurons (Ia inhibitory interneurons) were also associated with postsynaptic receptor clusters of variable shapes and configurations. Our results indicate that mechanisms regulating receptor clustering do so primarily in the context of the postsynaptic neuron identity and localization in the dendritic arbor. J. Comp. Neurol. 379:150-170, 1997. © 1997 Wiley-Liss, Inc

Cell-Type Specific Organization of Glycine Receptor Clusters in the Mammalian Spinal Cord

Glycinergic synapses play a major role in shaping the activity of spinal cord neurons. The spatial organization of postsynaptic receptors is likely to determine many functional parameters at these synapses and is probably related to the integrative capabilities of different neurons. In the present study, we have investigated the organization of gephyrin expression along the dendritic membranes of α- and γ-motoneurons, Ia inhibitory interneurons, and Renshaw cells. Gephyrin is a protein responsible for the postsynaptic clustering of glycine receptors, and the features of gephyrin and glycine receptor α1-subunit immunofluorescent clusters displayed similar characteristics on ventral horn spinal neurons. However, the density of clusters and their topographical organization and architecture varied widely in different neurons and in different dendritic regions. For motoneurons and Ia inhibitory interneurons, cluster size and complexity increased with distance from the soma, perhaps as a mechanism to enhance the influence of distal synapses. Renshaw cells were special in that they displayed an abundant complement of large and morphologically complex clusters concentrated in their somas and proximal dendrites. Serial electron microscopy confirmed that the various immunoreactivity patterns observed with immunofluorescence accurately parallel the variable organization of pre- and postsynaptic active zones of glycinergic synapses. Finally, synaptic boutons from single-labeled axons of glycinergic neurons (Ia inhibitory interneurons) were also associated with postsynaptic receptor clusters of variable shapes and configurations. Our results indicate that mechanisms regulating receptor clustering do so primarily in the context of the postsynaptic neuron identity and localization in the dendritic arbor. J. Comp. Neurol. 379:150-170, 1997. © 1997 Wiley-Liss, Inc

Cell-Type Specific Organization of Glycine Receptor Clusters in the Mammalian Spinal Cord

Glycinergic synapses play a major role in shaping the activity of spinal cord neurons. The spatial organization of postsynaptic receptors is likely to determine many functional parameters at these synapses and is probably related to the integrative capabilities of different neurons. In the present study, we have investigated the organization of gephyrin expression along the dendritic membranes of α- and γ-motoneurons, Ia inhibitory interneurons, and Renshaw cells. Gephyrin is a protein responsible for the postsynaptic clustering of glycine receptors, and the features of gephyrin and glycine receptor α1-subunit immunofluorescent clusters displayed similar characteristics on ventral horn spinal neurons. However, the density of clusters and their topographical organization and architecture varied widely in different neurons and in different dendritic regions. For motoneurons and Ia inhibitory interneurons, cluster size and complexity increased with distance from the soma, perhaps as a mechanism to enhance the influence of distal synapses. Renshaw cells were special in that they displayed an abundant complement of large and morphologically complex clusters concentrated in their somas and proximal dendrites. Serial electron microscopy confirmed that the various immunoreactivity patterns observed with immunofluorescence accurately parallel the variable organization of pre- and postsynaptic active zones of glycinergic synapses. Finally, synaptic boutons from single-labeled axons of glycinergic neurons (Ia inhibitory interneurons) were also associated with postsynaptic receptor clusters of variable shapes and configurations. Our results indicate that mechanisms regulating receptor clustering do so primarily in the context of the postsynaptic neuron identity and localization in the dendritic arbor. J. Comp. Neurol. 379:150-170, 1997. © 1997 Wiley-Liss, Inc

Clustering of Kv2.1 Potassium Channels in Spinal Neurons

Kv2.1 channel subunits underlie delayed rectifier potassium currents that are expressed in neurons throughout the mammalian CNS. We used confocal and electron microscopy to analyze the subcellular localization of these channels in a variety of rat spinal cord neurons, including motoneurons (MNs), interneurons, and dorsal spinocerebellar tract (DSCT) cells, using a commercially available monoclonal antibody against Kv2.1 (Upstate). Kv2.1 immunoreactivity appeared as distinct surface membrane clusters in somatic and proximal dendritic regions. Clusters varied in size and complexity depending on neuron type, with the largest clusters seen on MNs. Quantitative analysis of Kv2.1 channel clusters (n=225 \u27en face\u27 clusters) on MNs revealed a bimodal size distribution including small

Clustering of Kv2.1 Potassium Channels in Spinal Neurons

Kv2.1 channel subunits underlie delayed rectifier potassium currents that are expressed in neurons throughout the mammalian CNS. We used confocal and electron microscopy to analyze the subcellular localization of these channels in a variety of rat spinal cord neurons, including motoneurons (MNs), interneurons, and dorsal spinocerebellar tract (DSCT) cells, using a commercially available monoclonal antibody against Kv2.1 (Upstate). Kv2.1 immunoreactivity appeared as distinct surface membrane clusters in somatic and proximal dendritic regions. Clusters varied in size and complexity depending on neuron type, with the largest clusters seen on MNs. Quantitative analysis of Kv2.1 channel clusters (n=225 \u27en face\u27 clusters) on MNs revealed a bimodal size distribution including small