Resistance to cardiomyocyte hypertrophy in ae3-/- mice, deficient in the AE3 Cl-/HCO3- exchanger

Background: Cardiac hypertrophy is central to the etiology of heart failure. Understanding the molecular pathways promoting cardiac hypertrophy may identify new targets for therapeutic intervention. Sodium-proton exchanger (NHE1) activity and expression levels in the heart are elevated in many models of hypertrophy through protein kinase C (PKC)/MAPK/ERK/p90RSK pathway stimulation. Sustained NHE1 activity, however, requires an acid-loading pathway. Evidence suggests that the Cl-/HCO3- exchanger, AE3, provides this acid load. Here we explored the role of AE3 in the hypertrophic growth cascade of cardiomyocytes.Methods: AE3-deficient (ae3-/-) mice were compared to wildtype (WT) littermates to examine the role of AE3 protein in the development of cardiomyocyte hypertrophy. Mouse hearts were assessed by echocardiography. As well, responses of cultured cardiomyocytes to hypertrophic stimuli were measured. pH regulation capacity of ae3-/- and WT cardiomyocytes was assessed in cultured cells loaded with the pH-sensitive dye, BCECF-AM.Results: ae3-/- mice were indistinguishable from wild type (WT) mice in terms of cardiovascular performance. Stimulation of ae3-/- cardiomyocytes with hypertrophic agonists did not increase cardiac growth or reactivate the fetal gene program. ae3-/- mice are thus protected from pro-hypertrophic stimulation. Steady state intracellular pH (pHi) in ae3-/- cardiomyocytes was not significantly different from WT, but the rate of recovery of pHi from imposed alkalosis was significantly slower in ae3-/- cardiomyocytes.Conclusions: These data reveal the importance of AE3-mediated Cl-/HCO3- exchange in cardiovascular pH regulation and the development of cardiomyocyte hypertrophy. Pharmacological antagonism of AE3 is an attractive approach in the treatment of cardiac hypertrophy.Centro de Investigaciones Cardiovasculare

Resistance to cardiomyocyte hypertrophy in ae3-/- mice, deficient in the AE3 Cl-/HCO3- exchanger

Background: Cardiac hypertrophy is central to the etiology of heart failure. Understanding the molecular pathways promoting cardiac hypertrophy may identify new targets for therapeutic intervention. Sodium-proton exchanger (NHE1) activity and expression levels in the heart are elevated in many models of hypertrophy through protein kinase C (PKC)/MAPK/ERK/p90RSK pathway stimulation. Sustained NHE1 activity, however, requires an acid-loading pathway. Evidence suggests that the Cl-/HCO3- exchanger, AE3, provides this acid load. Here we explored the role of AE3 in the hypertrophic growth cascade of cardiomyocytes.Methods: AE3-deficient (ae3-/-) mice were compared to wildtype (WT) littermates to examine the role of AE3 protein in the development of cardiomyocyte hypertrophy. Mouse hearts were assessed by echocardiography. As well, responses of cultured cardiomyocytes to hypertrophic stimuli were measured. pH regulation capacity of ae3-/- and WT cardiomyocytes was assessed in cultured cells loaded with the pH-sensitive dye, BCECF-AM.Results: ae3-/- mice were indistinguishable from wild type (WT) mice in terms of cardiovascular performance. Stimulation of ae3-/- cardiomyocytes with hypertrophic agonists did not increase cardiac growth or reactivate the fetal gene program. ae3-/- mice are thus protected from pro-hypertrophic stimulation. Steady state intracellular pH (pHi) in ae3-/- cardiomyocytes was not significantly different from WT, but the rate of recovery of pHi from imposed alkalosis was significantly slower in ae3-/- cardiomyocytes.Conclusions: These data reveal the importance of AE3-mediated Cl-/HCO3- exchange in cardiovascular pH regulation and the development of cardiomyocyte hypertrophy. Pharmacological antagonism of AE3 is an attractive approach in the treatment of cardiac hypertrophy.Centro de Investigaciones Cardiovasculare

Oil and Cocoa in the Political Economy of Ghana-EU Relations: Whither Sustainable Development?

Oil and cocoa represent strategic export commodities for the Ghanaian economy, prioritised within the Ghana Shared Growth and Development Agenda. This article examines these sectors in the context of Ghana’s relations with the European Union (EU). Notably, the EU constitutes the most important market for Ghanaian exports. The European Commission, moreover, has pledged to tangibly assist private sector development in Ghana, with particular reference to the UN Sustainable Development Goals (SDGs). Through its focus on oil and cocoa, the article problematises certain aspects of EU aid and trade interventions with respect to normative SDG development pledges

The role of limited access to students from more diverse nonfeeder medical schools in creating diversity inequities in neurosurgical residency

OBJECTIVEImproving racial/ethnic diversity in neurosurgery is a long-standing issue that needs to be addressed. The positive correlation between medical students with home neurosurgery programs and successful matriculation into neurosurgical residency is well documented. In this article, the authors explored the relationship between decreased racial/ethnic diversity in neurosurgery residency programs and racial/ethnic diversity in feeder medical schools.METHODSThe authors conducted a standardized review of the literature to evaluate potential causes for decreased racial/ethnic diversity within neurosurgery. Additionally, they calculated the average enrollment of Black/African American medical students at the top 5 neurosurgery feeder medical schools (determined by Antar et al. following the 2014-2020 match cycles) during the 2021-2022 school year and compared that with the enrollment at US allopathic medical schools with the highest enrollment of Black/African American students. They also compared these two groups in terms of how many students they sent into neurosurgery residency programs from 2014 to 2020. For each of these comparisons, the authors conducted a two-sample t-test to evaluate correlation between these two variables.RESULTSThere was significantly lower average enrollment of Black/African American students at the top 5 feeder medical programs into neurosurgery residency (80.6 ± 8.32) compared with the top 5 medical schools with Black/African American enrollment in the 2021-2022 school year (279 ± 122.00, p < 0.05). The authors also found a significant increase in the number of students entering neurosurgery residency programs between the top 5 feeder medical programs into neurosurgery residency (30.8 ± 6.06) and the top 5 medical programs for Black/African American enrollment (6 ± 6.16, p < 0.0001).CONCLUSIONSIn this paper, the authors examined, through a Black/African American lens, the role of racial/ethnic diversity in medical schools that historically send many students to neurosurgery residency. This study sought to provide insight into this problem and examine how Black/African American students from nonfeeder medical schools are disproportionately affected. The authors' findings suggest that the lack of Black/African American representation in neurosurgery is strongly correlated with the diversity efforts of medical schools. Lastly, the authors highlight the University of Miami's Summer Research Scholarship in Neurosurgery for Medical Students and other programs as potential solutions to combat the lack of racial/ethnic diversity in neurosurgery

Pars Interarticularis Fractures Treated with Minimally Invasive Surgery: A Literature Review

Recurrent stress on the isthmic pars interarticularis often leads to profound injury and symptom burden. When conservative and medical management fail, there are various operative interventions that can be used. The current review details the common clinical presentation and treatment of pars injury, with a special focus on the emerging minimally invasive procedures used in isthmic pars interarticularis repair. PubMed and Google Scholar database literature reviews were conducted. The keywords and phrases that were searched include but were not limited to; "history of spondylolysis", "pars interarticularis", "pars defect", "conventional surgical repair of pars", and "minimally invasive repair of pars". The natural history, conventional presentation, etiology, risk factors, and management of pars interarticularis injury are discussed by the authors. The surgical interventions described include the Buck's repair, Morscher Screw-Hook repair, Scott's Wiring technique, and additional pedicle screw-based repairs. Minimally invasive techniques are also reviewed, including the Levi technique. Surgical intervention has been proven to be safe and effective in managing pars interarticularis fractures. However, minimally invasive techniques often provide additional benefit to patients such as reducing damage of surrounding structures, decreasing postoperative pain, and limiting the time away from sports and other activities

Is There a Link Between Exchange Rate Pass-Through and the Monetary Regime: Evidence from Sub-Saharan Africa and Latin America

Dollarization, Exchange rate pass through, Monetary union, E00, F00, F30,

Misperception of drivers of risk alters willingness to adapt in the case of sargassum influxes in West Africa

Since 2011, large influxes of a brown macroalgae (pelagic sargassum seaweed) have proliferated across the Tropical Atlantic basin, its dispersal and seasonality theorized to be driven by localized and large scale winds and currents, in combination with changes in the Atlantic Meridional Mode and ocean upwelling. These influxes seasonally affect coastal populations across the breadth of the Tropical Atlantic (from central America to West Africa), causing damage to: economies, marine-based and non-marine coastal livelihoods, social functioning, health, ecology, and the aesthetics of the local environment. We use the ongoing sargassum influx in West Africa as a case study of adaptation to an emergent (and compound) risk in progress that also contributes to the empirical gap in sargassum adaptation research in West Africa. The research, in four sites in the Western Region of Ghana employs data from 16 focus group discussions, six key informant interviews, and participant observation. We finds that due to a series of coincidences, participant communities perceive that sargassum influxes were seeded by and then annually driven by oil and gas exploration in Western Ghana. This is in contrast to scientific research that indicates that pelagic sargassum was initially seeded in the tropical Atlantic basin (from the Sargasso Sea) in 2010 following an anomalous weather event in winter 2009–2010. Following Rogers’ Protection Motivation Theory, we explore the sources of information and the processing of that information to understand the divergence between scientific and community perceptions of the physical drivers. We find that community perceptions of oil and gas company responsibility for causing the sargassum problem leads the communities to perceive that the oil and gas companies should be responsible for the clean-up activities. Communities are further constrained by a perceived lack of capacity to act. Solutions to address this adaptation impasse could involve the government working with communities and the oil and gas industry to clarify the actual drivers of sargassum. Such guidance may open opportunities for the government and industry to work with communities to address misperceptions of the scientific nature of the influxes. Collaborative approaches, while addressing extant tensions, may also change the narrative about the problem, support affected communities to engage with adaptive measures, including re-use opportunities, and enhance community capacity to act. As a present-day emergent risk, pelagic sargassum provides an unusual yet contemporary empirical study of real-time adaptation and the central role of perceptions in shaping proactive adaptation and seeking exploitable opportunities from new environmental risks