10 research outputs found
Evaluation of participatory approaches for responsive research & development in Ethiopia: success factors
Perinatal palliative care in sub-Saharan Africa: recommendations for practice, future research, and guideline development
Worldwide, sub-Saharan Africa has the highest burden of global neonatal mortality (43%) and neonatal mortality rate (NMR): 27 deaths per 1,000 live births. The WHO recognizes palliative care (PC) as an integral, yet underutilized, component of perinatal care for pregnancies at risk of stillbirth or early neonatal death, and for neonates with severe prematurity, birth trauma or congenital anomalies. Despite bearing a disproportionate burden of neonatal mortality, many strategies to care for dying newborns and support their families employed in high-income countries (HICs) are not available in low-and-middle-income countries (LMICs). Many institutions and professional societies in LMICs lack guidelines or recommendations to standardize care, and existing guidelines may have limited adherence due to lack of space, equipment, supplies, trained professionals, and high patient load. In this narrative review, we compare perinatal/neonatal PC in HICs and LMICs in sub-Saharan Africa to identify key areas for future, research-informed, interventions that might be tailored to the local sociocultural contexts and propose actionable recommendations for these resource-deprived environments that may support clinical care and inform future professional guideline development
Preventing mother-to-child transmission in Guayaquil, Ecuador: HIV knowledge and risk perception
Valuing Natural Forest Resources: An Application of Contingent Valuation Method on Adaba-Dodola Forest Priority Area, Bale Mountains, Ethiopia
A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway.
The stress-responsive epigenetic repressor histone deacetylase 4 (HDAC4) regulates cardiac gene expression. Here we show that the levels of an N-terminal proteolytically derived fragment of HDAC4, termed HDAC4-NT, are lower in failing mouse hearts than in healthy control hearts. Virus-mediated transfer of the portion of the Hdac4 gene encoding HDAC4-NT into the mouse myocardium protected the heart from remodeling and failure; this was associated with decreased expression of Nr4a1, which encodes a nuclear orphan receptor, and decreased NR4A1-dependent activation of the hexosamine biosynthetic pathway (HBP). Conversely, exercise enhanced HDAC4-NT levels, and mice with a cardiomyocyte-specific deletion of Hdac4 show reduced exercise capacity, which was characterized by cardiac fatigue and increased expression of Nr4a1. Mechanistically, we found that NR4A1 negatively regulated contractile function in a manner that depended on the HBP and the calcium sensor STIM1. Our work describes a new regulatory axis in which epigenetic regulation of a metabolic pathway affects calcium handling. Activation of this axis during intermittent physiological stress promotes cardiac function, whereas its impairment in sustained pathological cardiac stress leads to heart failure
The modeled and observed response of Lake Spokane hypolimnetic dissolved oxygen concentrations to phosphorus inputs
<p>Brett MT, Ahopelto SK, Brown HK, Brynestad BE, Butcher TW, Coba EE, Curtis CA, Dara JT, Doeden KB, Evans KR, Fan L, Finley JD, Garguilo NJ, Gebreeyesus SM, Goodman MK, Gray KW, Grinnell C, Gross KL, Hite BRE, Jones AJ, Kenyon PT, Klock AM, Koshy RE, Lawler AM, Lu M, Martinkosky L, Miller-Schulze JR, Nguyen QTN, Runde ER, Stultz JM, Wang S, White FP, Wilson CH, Wong AS, Wu SY, Wurden PG, Young TR, Arhonditsis GB. 2016. The modeled and observed response of Lake Spokane hypolimnetic dissolved oxygen concentrations to phosphorus inputs. Lake Reserv Manage. 32:246–258.</p> <p>Lake Spokane, a reservoir in eastern Washington State, was previously hypereutrophic due to phosphorus discharges from the City of Spokane wastewater treatment plant (WWTP). This reservoir subsequently recovered to a meso-oligotrophic state after implementation of advanced phosphorus removal. The present study tested whether the mechanistic Lake Spokane water quality (WQ) model realistically represents the sensitivity of this reservoir's hypolimnetic oxygen concentrations to phosphorus inputs. We compared the observed relationship between the mean summer input total phosphorus concentration (TP<sub>IN</sub>) and the minimum volume weighted hypolimnetic dissolved oxygen concentration (DO<sub>MIN</sub>) to model values for conditions ranging from hypereutrophic to oligotrophic. Prior to advanced phosphorus removal, TP<sub>IN</sub> and DO<sub>MIN</sub> averaged 86 ± 37 (SD) µg/L and 1.4 ± 1.3 mg/L, respectively. Currently (2010–2014), these values average 14 ± 3 µg/L and 6.5 ± 0.8 mg/L, respectively. By contrast, the model's DO<sub>MIN</sub> response for similar TP<sub>IN</sub> concentrations was much less pronounced, with hypereutrophic and contemporary DO<sub>MIN</sub> averaging 3.8 ± 0.4 and 4.7 ± 0.04 mg/L, respectively. The model also has a structural DO deficit (saturated DO − DO<sub>MIN</sub>) of 5.3 mg/L that was evident when all TP inputs to the reservoir were set to zero. Similarly, when all WWTP effluent sources were set to TP<sub>EFF</sub> = 0 µg/L, the reservoir epilimnetic TP concentrations were ≈8 µg/L higher than the Spokane River inputs. The water quality model indicates that even if effluent phosphorus concentrations are reduced to zero, the dissolved oxygen goals for Lake Spokane cannot be met.</p
A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway
The stress-responsive epigenetic repressor histone deacetylase 4 (HDAC4) regulates cardiac gene expression. Here we show that the levels of an N-terminal proteolytically derived fragment of HDAC4, termed HDAC4-NT, are lower in failing mouse hearts than in healthy control hearts. Virus-mediated transfer of the portion of the Hdac4 gene encoding HDAC4-NT into the mouse myocardium protected the heart from remodeling and failure; this was associated with decreased expression of Nr4a1, which encodes a nuclear orphan receptor, and decreased NR4A1-dependent activation of the hexosamine biosynthetic pathway (HBP). Conversely, exercise enhanced HDAC4-NT levels, and mice with a cardiomyocyte-specific deletion of Hdac4 show reduced exercise capacity, which was characterized by cardiac fatigue and increased expression of Nr4a1. Mechanistically, we found that NR4A1 negatively regulated contractile function in a manner that depended on the HBP and the calcium sensor STIM1. Our work describes a new regulatory axis in which epigenetic regulation of a metabolic pathway affects calcium handling. Activation of this axis during intermittent physiological stress promotes cardiac function, whereas its impairment in sustained pathological cardiac stress leads to heart failure