Global health partnerships: building multi-national collaborations to achieve lasting improvements in maternal and neonatal health

Abstract Background In response to health care challenges worldwide, extensive funding has been channeled to the world’s most vulnerable health systems. Funding alone is not sufficient to address the complex issues and challenges plaguing these health systems. To see lasting improvement in maternal and infant health outcomes in the developing world, a global commitment to the sharing of knowledge and resources through international partnerships is critical. But partnerships that merely introduce western medical techniques and protocols to low resource settings, without heeding the local contexts, are misguided and unsustainable. Forming partnerships with mutual respect, shared vision, and collaborative effort is needed to ensure that all parties, irrespective of whether they belong to resource rich or resource poor settings, learn from each other so that meaningful and sustained system strengthening can take place. Methods In this paper, we describe the partnership building model of an international NGO, Kybele, which is committed to achieving childbirth safety through sustained partnerships in low resource settings. The Kybele model adapts generic stages of successful partnerships documented in the literature to four principles relevant to Kybele’s work. A multiple-case study approach is used to demonstrate how the model is applied in different country settings. Results The four principle of Kybele’s partnership model are robust drivers of successful partnerships in diverse country settings. Conclusions Much has been written about the need for multi-country partnerships to achieve sustainable outcomes in global health, but few papers in the literature describe how this has been achieved in practice. A strong champion, support and engagement of stakeholders, co-creation of solutions with partners, and involvement of partners in the delivery of solutions are all requirements for successful and sustained partnerships

Stability mechanisms of a thermophilic laccase probed by molecular dynamics.

Laccases are highly stable, industrially important enzymes capable of oxidizing a large range of substrates. Causes for their stability are, as for other proteins, poorly understood. In this work, multiple-seed molecular dynamics (MD) was applied to a Trametes versicolor laccase in response to variable ionic strengths, temperatures, and glycosylation status. Near-physiological conditions provided excellent agreement with the crystal structure (average RMSD ∼0.92 Å) and residual agreement with experimental B-factors. The persistence of backbone hydrogen bonds was identified as a key descriptor of structural response to environment, whereas solvent-accessibility, radius of gyration, and fluctuations were only locally relevant. Backbone hydrogen bonds decreased systematically with temperature in all simulations (∼9 per 50 K), probing structural changes associated with enthalpy-entropy compensation. Approaching T opt (∼350 K) from 300 K, this change correlated with a beginning "unzipping" of critical β-sheets. 0 M ionic strength triggered partial denucleation of the C-terminal (known experimentally to be sensitive) at 400 K, suggesting a general salt stabilization effect. In contrast, F(-) (but not Cl(-)) specifically impaired secondary structure by formation of strong hydrogen bonds with backbone NH, providing a mechanism for experimentally observed small anion destabilization, potentially remedied by site-directed mutagenesis at critical intrusion sites. N-glycosylation was found to support structural integrity by increasing persistent backbone hydrogen bonds by ∼4 across simulations, mainly via prevention of F(-) intrusion. Hydrogen-bond loss in distinct loop regions and ends of critical β-sheets suggest potential strategies for laboratory optimization of these industrially important enzymes

The Role of Mislocalized Phototransduction in Photoreceptor Cell Death of Retinitis Pigmentosa

Most of inherited retinal diseases such as retinitis pigmentosa (RP) cause photoreceptor cell death resulting in blindness. RP is a large family of diseases in which the photoreceptor cell death can be caused by a number of pathways. Among them, light exposure has been reported to induce photoreceptor cell death. However, the detailed mechanism by which photoreceptor cell death is caused by light exposure is unclear. In this study, we have shown that even a mild light exposure can induce ectopic phototransduction and result in the acceleration of rod photoreceptor cell death in some vertebrate models. In ovl, a zebrafish model of outer segment deficiency, photoreceptor cell death is associated with light exposure. The ovl larvae show ectopic accumulation of rhodopsin and knockdown of ectopic rhodopsin and transducin rescue rod photoreceptor cell death. However, knockdown of phosphodiesterase, the enzyme that mediates the next step of phototransduction, does not. So, ectopic phototransduction activated by light exposure, which leads to rod photoreceptor cell death, is through the action of transducin. Furthermore, we have demonstrated that forced activation of adenylyl cyclase in the inner segment leads to rod photoreceptor cell death. For further confirmation, we have also generated a transgenic fish which possesses a human rhodopsin mutation, Q344X. This fish and rd10 model mice show photoreceptor cell death caused by adenylyl cyclase. In short, our study indicates that in some RP, adenylyl cyclase is involved in photoreceptor cell death pathway; its inhibition is potentially a logical approach for a novel RP therapy

Pleiotropic Effects of Sox2 during the Development of the Zebrafish Epithalamus

The zebrafish epithalamus is part of the diencephalon and encompasses three major components: the pineal, the parapineal and the habenular nuclei. Using sox2 knockdown, we show here that this key transcriptional regulator has pleiotropic effects during the development of these structures. Sox2 negatively regulates pineal neurogenesis. Also, Sox2 is identified as the unknown factor responsible for pineal photoreceptor prepatterning and performs this function independently of the BMP signaling. The correct levels of sox2 are critical for the functionally important asymmetrical positioning of the parapineal organ and for the migration of parapineal cells as a coherent structure. Deviations from this strict control result in defects associated with abnormal habenular laterality, which we have documented and quantified in sox2 morphants

Epidural hematoma following low molecular weight heparin prophylaxis and spinal anesthesia for cesarean delivery

Epidural hematoma is a very uncommon complication of spinal anesthesia. Its incidence has been reported to be between 1:200 000-250 000 in the obstetric population following neuraxial anesthesia. Cesarean delivery increases the risk of maternal venous thromboembolism significantly and recommendations to decrease its incidence and morbidity have been developed. Strategies to decrease venous thromboembolism include pharmacologic prophylaxis with unfractionated or low molecular weight heparin. We report a case of spinal-epidural hematoma occurring in a parturient who received spinal anesthesia for a planned, repeat cesarean delivery after low molecular weight heparin thromboprophylaxis.12 month embargo; available online 26 September 2018.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Immunohistochemical localization of mast cells and mast cell-nerve interactions in oral lichen planus

OBJECTIVES: Mast cell mediators are likely to be involved in at least some aspects of the immunopathogenesis of oral lichen planus (OLP). The aim of this project was to map mast cell populations in OLP and identify possible sites of mast cell-nerve interactions. MATERIALS AND METHODS: Monoclonal antibodies specific for tryptase and neurofilaments were used to identify mast cells and nerves respectively in an immunohistochemical study of OLP (n = 25) and normal oral buccal mucosa (NOBM) (n = 13) using a double-labelling protocol. Data analysis used paired t-test, multiway analysis of variance and Wilcoxon rank tests. RESULTS: Morphometric analyses showed the greatest mast cell density in the most superficial of the three depth layers examined in OLP, an increase of 130% compared with NOBM. Mast cells associated with neurofilaments ranged from 21.9% in OLP to 10.2% in NOBM. Mean epithelial thickness was significantly lower in OLP (P < 0.001) but without a strong correlation with mast cell density. CONCLUSIONS: Increased mast cell and mast cell-nerve interactions in OLP suggest both a controlling role over the lesional cell populations and a secondary role to the immune response once this becomes established