Explaining Disparities in Use of Skilled Birth Attendants in Developing Countries: A Conceptual Framework

Despite World Health Organization recommendations that all women deliver with a skilled birth attendant (SBA), research continues to demonstrate large disparities in use of SBAs by socioeconomic status (SES). Yet few quantitative studies empirically examine the factors underlying these disparities, due in part to the fact that current models do not provide clear pathways—with measurable mediators—for how distal factors like SES may affect maternal health-seeking behaviors like delivering with SBAs. We propose the Disparities in Skilled Birth Attendance (DiSBA) framework for examining the determinants of use of SBAs. We posit that three proximal factors directly affect use of SBAs: perceived need, perceived accessibility of maternal health services, and perceived quality of care. Distal factors like SES affect use of SBAs indirectly through these proximal factors, and the effects can be measured. We test the assumptions of the DiSBA framework using data from the Ghana Maternal Health Survey. The analytic techniques we use include logistic regression with mediation analysis to examine the intervening effects. We find that our proxies for perceived access, perceived need, and perceived quality of care account for approximately 23% of the difference between women with no education and those with primary school education, and about 55% of the difference between women in the lowest wealth quintile and those in the middle wealth quintiles. This study suggests that proximal factors are worthy of increased attention in terms of measurement, data collection, analysis, programmatic efforts, and policy interventions, as these factors are potentially more amenable to change than the distal factors. The effects of proximal factors are also likely context specific, thus sufficient understanding in different contexts is essential to developing appropriate interventions.     

Testing the Hypothesis of Biofilm as a Source for Soft Tissue and Cell-Like Structures Preserved in Dinosaur Bone

Recovery of still-soft tissue structures, including blood vessels and osteocytes, from dinosaur bone after demineralization was reported in 2005 and in subsequent publications. Despite multiple lines of evidence supporting an endogenous source, it was proposed that these structures arose from contamination from biofilm-forming organisms. To test the hypothesis that soft tissue structures result from microbial invasion of the fossil bone, we used two different biofilm-forming microorganisms to inoculate modern bone fragments from which organic components had been removed. We show fundamental morphological, chemical and textural differences between the resultant biofilm structures and those derived from dinosaur bone. The data do not support the hypothesis that biofilm-forming microorganisms are the source of these structures.     

Perinatal physiology in cloned and normal calves: hematologic and biochemical profiles

Although a majority of clones are born normal and apparently healthy, mortality rates of nearly 30% are described in many reports. Such losses are a major limitation of cloning technology and represent substantial economic investment as well as justifiable animal health and welfare concerns. Prospective, controlled studies are needed to understand fully the causes of neonatal mortality in clones and to develop preventive and therapeutic strategies to minimize losses. We report here the findings of studies on the hematologic and biochemical profiles of cloned and control calves in the immediate 48-h postpartum period. Cloned calves were similar to control calves for a majority of parameters studied including blood gases, concentrations of plasma proteins, minerals and electrolytes, and white blood cell, neutrophil, lymphocyte, and platelet counts. The most notable differences between clones and controls in this study were reduced red- and white-blood cell counts in clones at birth and 1 h of age. As a group, plasma electrolyte concentrations were more variable in clones, and the variability tended to be shifted either higher (sodium, chloride) or lower (potassium, bicarbonate) than in controls. Previously, we noted differences in carbohydrate parameters, the length of time required for clones to make the neonatal adaptation to life ex utero, and morphology of the cloned placenta. Taken together, our findings suggest that cloned calves experience greater difficulty adjusting to life ex utero and that further research is warranted to determine the nature of the relationship between the physiological differences noted here in clones at birth and concomitant abnormal placental morphology.     

Cloning and functional expression of the cytoplasmic form of rat aminopeptidase P

A rat cytoplasmic aminopeptidase P was purified from liver cytosol with a procedure including an affinity elution step with 3 microM inositol 1,3,4-trisphosphate. Proteolytic fragments were generated, sequenced and the enzyme was cloned from a rat liver cDNA library. The structure shows high (87.8% and 95.5%, respectively) sequence identity at the nucleotide and amino acid levels with the previously described human putative cytoplasmic aminopeptidase P. The cloned rat enzyme was functionally expressed in Escherichia coli and also in COS-1 cells. Western blot analysis, using an antibody generated against the recombinant protein, and Northern blot hybridization showed ubiquitous expression of the protein in different tissues with the highest expression level in the testis.     

Adverse effects of myasthenia gravis on rat phrenic diaphragm contractile performance.

Myasthenia gravis has variable effects on the respiratory system, ranging from no abnormalities to life-threatening respiratory failure. Studies characterized diaphragm muscle contractile performance in rat autoimmune myasthenia gravis. Rats received monoclonal antibody that recognizes acetylcholine receptor determinants (or inactive antibody); 3 days later, phrenic nerve and diaphragm were studied in vitro. Myasthenic rats segregated into two groups, those with normal vs. impaired limb muscle function when tested in intact animals ("mild" and "severe" myasthenic). Baseline diaphragm twitch force was reduced for both severe (P < 0.01) and mild (P < 0.05) myasthenic compared with control animals (twitch force: normal 1,352 +/- 140, mild myasthenic 672 +/- 99, severe myasthenic 687 +/- 74 g/cm2). However, only severe myasthenic diaphragm had impaired diaphragm endurance, based on significantly (P < 0.05) accelerated rate of peak force decline during the initial period of stimulation (0.02 + 0.02, 0.03 +/- 0.01, and 0.09 +/- 0.01%/pulse for normal, mild myasthenic, and severe myasthenic, respectively, during continuous stimulation) and intratrain fatigue (up to 30.5 +/- 7.4% intratrain force drop in severe myasthenic vs. none in normal and mild myasthenic, P < 0.01). Furthermore, compared with continuous stimulation, intermittent stimulation had a protective effect on force of severe myasthenic diaphragm (force after 2,000 pulses was 31.4 +/- 2.0% of initial during intermittent stimulation vs. 13.0 +/- 2.1% of initial during continuous stimulation, P < 0.01) but not on normal diaphragm. These data indicate that baseline force and fatigue may be affected to different extents by varying severity of myasthenia gravis and furthermore provide a mechanism by which alterations in breathing pattern may worsen respiratory muscle function in neuromuscular diseases.     

Melatonin and activity rhythm responses to light pulses in mice with the Clock mutation

Melatonin and wheel-running rhythmicity and the effects of acute and chronic light pulses on these rhythms were studied in Clock(Delta19) mutant mice selectively bred to synthesize melatonin. Homozygous melatonin-proficient Clock(Delta19) mutant mice (Clock(Delta19/Delta19)-MEL) produced melatonin rhythmically, with peak production 2 h later than the wild-type controls (i.e., just before lights on). By contrast, the time of onset of wheel-running activity occurred within a 20-min period around lights off, irrespective of the genotype. Melatonin production in the mutants spontaneously decreased within 1 h of the expected time of lights on. On placement of the mice in continuous darkness, the melatonin rhythm persisted, and the peak occurred 2 h later in each cycle over the first two cycles, consistent with the endogenous period of the mutant. This contrasted with the onset of wheel-running activity, which did not shift for several days in constant darkness. A light pulse around the time of expected lights on followed by constant darkness reduced the expected 2-h delay of the melatonin peak of the mutants to approximately 1 h and advanced the time of the melatonin peak in the wild-type mice. When the Clock(Delta19/Delta19)-MEL mice were maintained in a skeleton photoperiod of daily 15-min light pulses, a higher proportion entrained to the schedule (57%) than melatonin-deficient mutants (9%). These results provide compelling evidence that mice with the Clock(Delta19) mutation express essentially normal rhythmicity, albeit with an underlying endogenous period of 26-27 h, and they can be entrained by brief exposure to light. They also raise important questions about the role of Clock in rhythmicity and the usefulness of monitoring behavioral rhythms compared with hormonal rhythms.     

Neurotensin stimulates IL-8 expression in human colonic epithelial cells through Rho GTPase-mediated NF-kappa B pathways

Neurotensin (NT), a neuropeptide highlyexpressed in the gastrointestinal tract, participates in thepathophysiology of intestinal inflammation. We recently showed that NTstimulates interleukin-8 (IL-8) expression in NCM460 nontransformedhuman colonic epithelial cells via both mitogen-activating proteinkinase (MAPK)- and NF-B-dependent pathways. However, the molecularmechanism by which NT induces expression of proinflammatory cytokinessuch as IL-8 has not been investigated. In this study we show thatinhibition of endogenous Rho family proteins (RhoA, Rac1, and Cdc42) bytheir respective dominant negative mutants inhibits NT-induced IL-8protein production and promoter activity. Western blot experimentsdemonstrated that NT strongly activated RhoA, Rac1, and Cdc42.Overexpression of the dominant negative mutants of RhoA, Rac1, andCdc42 significantly inhibited NT-induced NF-B-dependent reportergene expression and NF-B DNA binding activity. NT also stimulatedp38 MAPK phosphorylation, and overexpression of dominant negativemutants of RhoA, Rac1, and Cdc42 did not significantly alter p38 andERK1/2 phosphorylation in response to NT. Together, our findingsindicate that NT-stimulated IL-8 expression is mediated via aRho-dependent NF-B-mediated pathway.

     

Modulation of human fibroblast gap junction intercellular communication by hyaluronan

The composition of the extracellular matrix changes during dermal repair. Initially, hyaluronan (HA) concentration is high, however, by day 3, HA is eliminated. HA optimizes collagen organization within granulation tissue. One possible mechanism of HA modulation of collagen packing is through the promotion of gap junction intercellular communication (GJIC). Gap junctions are gated channels that allow rapid intercellular communication and synchronization of coupled cell activities. The gap junction channel is composed of connexin (Cx) proteins that form a gated channel between coupled cells. HA is reported to enhance Cx43 expression in transformed fibroblasts. GJIC was quantified by the scrape loading technique and reported as a coupling index. The coupling index for human dermal fibroblasts was 4.6 +/- 0.2, while the coupling index for fibroblasts treated with HA more than doubled to 10.6 +/- 0.7. By Western blot analysis no differences were appreciated in the protein levels of Cx43 or beta-catenin, a protein involved in the translocation of Cx to the cell surface. By immuno-histology Cx43 and beta-catenin were evenly distributed throughout the cell in controls, but in cells treated with HA these proteins were co-localized to the cell surface. Coupled fibroblasts are reported to enhance the organization of collagen fibrils. It is proposed that HA increases the accumulation of Cx43 and beta-catenin on the cell surface, leading to greater GJIC and enhanced collagen organization.