Dialysis enrollment patterns in Guatemala: Evidence of the chronic kidney disease of non-traditional causes epidemic in Mesoamerica

BACKGROUND: In western Nicaragua and El Salvador, chronic kidney disease (CKD) is highly prevalent and generally affects young, male, agricultural (usually sugar cane) workers without the established CKD risk factors. It is yet unknown if the prevalence of this CKD of Non-Traditional causes (CKDnT) extends to the northernmost Central American country, Guatemala. Therefore, we sought to compare dialysis enrollment rates by region, municipality, sex, daily temperature, and agricultural production in Guatemala and assess if there is a similar CKDnT distribution pattern as in Nicaragua and El Salvador. METHODS: The National Center for Chronic Kidney Disease Treatment (Unidad Nacional de Atención al Enfermo Renal Crónico) is the largest provider of dialysis in Guatemala. We used population, Human Development Index, literacy, and agricultural databases to assess the geographic, economic, and educational correlations with the National Center for Chronic Kidney Disease Treatment’s hemodialysis and peritoneal dialysis enrollment database. Enrollment rates (per 100 000) inhabitants were compared by region and mapped for comparison to regional agricultural and daytime temperature data. The distribution of men and women enrolled in dialysis were compared by region using Fisher’s exact tests. Spearman’s rank correlation coefficients were calculated. RESULTS: Dialysis enrollment is higher in the Southwest compared to the rest of the country where enrollees are more likely (p < 0.01) to be male (57.8%) compared to the rest of the country (49.3%). Dialysis enrollment positively correlates with Human Development Index and literacy rates. These correlations are weaker in the agricultural regions (predominantly sugar cane) of Southwest Guatemala. CONCLUSIONS: In Guatemala, CKDnT incidence may have a similar geographic distribution as Nicaragua and El Salvador (higher in the high temperature and sugar cane growing regions). Therefore, it is likely that the CKNnT epidemic extends throughout the Mesoamerican region

Recombinant human erythropoietin (rHuEPO) increases endothelin-1 release by endothelial cells

Recombinant human erythropoietin (rHuEPO) increases endothelin-1 release by endothelial cells. Hypertension is a major complication of rHuEPO therapy in hemodialysis (HD) patients. We have previously reported that patients receiving rHuEPO intravenously (i.v.) had higher mean arterial pressure (MAP) and plasma endothelin-1 (ET-1) levels than those in which the hormone was administered subcutaneously (s.c). To test whether the increased serum ET-1 levels associated with i.v. rHuEPO administration are the result of a direct effect of the hormone on ET-1 release by the endothelial cells (EC), we examined the effects of rHuEPO in vitro. Bovine pulmonary artery endothelial cells (BPAEC) were exposed to doses of rHuEPO of 0.8; 1.6; 3.3 and 6.6 U/ml. A 24 hour-time course showed maximal ET-1 production at 12 hours for all the doses tested. A significant increase in cell proliferation over controls was observed at 24 hours, for all rHuEPO doses, and no correlation was found between ET-1 values and cell proliferation. Inhibition of protein synthesis by cycloheximide (10 µg/ml) abolished the stimulation of ET-1 release by rHuEPO. Thrombin (4 U/ml) and angiotensin II (10-7 M), two potent stimulators of ET-1 release, had additive effects to those of rHuEPO. Specific thrombin and angiotensin II antagonists blocked these additive effects, reducing ET-1 release to the level of rHuEPO stimulation alone. In summary, rHuEPO stimulates vascular EC in culture to increase ET-1 release through an increase in synthesis and in a time dependent fashion. The routes of stimulation seem to differ from other known ET-1 secretogoges. Our data also confirm a significant mitogenic effect of rHuEPO on the endothelial cell

Prevalencia de enfermedad renal crónica de causa no tradicional (ERCnT) en pacientes en hemodiálisis de la costa sur de Guatemala

La enfermedad renal crónica (ERC) de causa no tradicional (ERCnT) se presenta frecuentemente en la costa sur de América Central y regiones de Sri Lanka. Poco se sabe de esta patología pero, afecta poblaciones jóvenes, trabajadores de la agroindustria que se exponen al golpe de calor, viven debajo de 200 m.snm, tienden a tener poca proteinuria y no se asocian a factores tradicionales de ERC, además se reconocen otros factores como, deshidratación frecuente, rabdomiolisis, uso de AINES, contexto de pobreza, bajo peso al nacer y malnutrición. Se estableció la prevalencia de pacientes con ERCnT y los factores asociados a través de un estudio descriptivo de corte transversal en donde se entrevistaron 242 pacientes que reciben tratamiento de hemodiálisis en diferentes unidades de la costa sur (Escuintla, Mazatenango y Retalhuleu). Los pacientes fueron clasificados en diabéticos, hipertensos, obesos o si ninguno de esos factores. Se analizó la relación entre pacientes con factores no tradicionales de ERC: ocupación, demográficos, hábitos, altitud y tiempo en llegar a su clínica de diálisis, usando un análisis multivariado de regresión logística. Se encontró que 171 (71%) pacientes no presentaron factores tradicionales de ERC. Aunque la ocupación de agricultor es la más común, únicamente alcanzó significancia estadística la edad &lt;50 años y el tiempo &gt;30 min que tardan en desplazarse a la clínica de diálisis. El uso de AINES y consumo de bebidas carbonatadas fue descrito como frecuente. La prevalencia de ERCNT en pacientes que reciben hemodiálisis en la costa sur de Guatemala es alta. Es el mismo fenómeno reportado en El Salvador y Nicaragua. Queda entonces demostrado que la ERCnT también se presenta en la costa sur de Guatemala

A crossover intervention trial evaluating the efficacy of a chlorhexidine-impregnated sponge in reducing catheter-related bloodstream infections among patients undergoing hemodialysis

BACKGROUND: Catheter-related bloodstream infections (BSI) account for the majority of hemodialysis-related infections. There are no published data on the efficacy of the chlorhexidine-impregnated foam dressing at reducing catheter-related BSI in hemodialysis patients. DESIGN: Prospective non-blinded cross-over intervention trial to determine the efficacy of a chlorhexidine-impregnated foam dressing (Biopatch®) to reduce catheter-related BSI in hemodialysis patients. SETTING: Two outpatient dialysis centers PATIENTS: A total of 121 patients who were dialyzed through tunneled central venous catheters received the intervention during the trial. METHODS: The primary outcome of interest was the incidence of catheter-related bloodstream infections. A nested cohort study of all patients who received the Biopatch® Antimicrobial Dressing was also conducted. Backward stepwise logistic regression analysis was used to determine independent risk factors for development of BSI. RESULTS: 37 bloodstream infections occurred in the intervention group for a rate of 6.3 BSIs/1000 dialysis sessions and 30 bloodstream infections in the control group for a rate of 5.2 BSIs/1000 dialysis sessions and [RR 1.22, CI (0.76, 1.97); P=0.46]. The Biopatch® Antimicrobial Dressing was well-tolerated with only two patients (<2%) experiencing dermatitis that led to its discontinuation. The only independent risk factor for development of BSI was dialysis treatment at one dialysis center [aOR 4.4 (1.77, 13.65); P=0.002]. Age ≥ 60 years [aOR 0.28 (0.09, 0.82); P=0.02] was associated with lower risk for BSI. CONCLUSION: The use of a chlorhexidine-impregnated foam dressing (Biopatch®) did not decrease catheter-related BSIs among hemodialysis patients with tunneled central venous catheters

P1 and P2 protein heterodimer binding to the P0 protein of Saccharomyces cerevisiae is relatively non-specific and a source of ribosomal heterogeneity

The ribosomal stalk is formed by four acidic phosphoproteins in Saccharomyces cerevisiae, P1α, P1β, P2α and P2β, which form two heterodimers, P1α/P2β and P1β/P2α, that preferentially bind to sites A and B of the P0 protein, respectively. Using mutant strains carrying only one of the four possible P1/P2 combinations, we found a specific phenotype associated to each P1/P2 pair, indicating that not all acidic P proteins play the same role. The absence of one P1/P2 heterodimer reduced the rate of cell growth by varying degrees, depending on the proteins missing. Synthesis of the 60S ribosomal subunit also decreased, particularly in strains carrying the unusual P1α–P2α or P1β–P2β heterodimers, although the distinct P1/P2 dimers are bound with similar affinity to the mutant ribosome. While in wild-type strains the B site bound P1β/P2α in a highly specific manner and the A site bound the four P proteins similarly, both the A and B binding sites efficiently bound practically any P1/P2 pair in mutant strains expressing truncated P0 proteins. The reported results support that while most ribosomes contain a P1α/P2β–P0–P1β/P2α structure in normal conditions, the stalk assembly mechanism can generate alternative compositions, which have been previously detected in the cell

A ética do silêncio racial no contexto urbano: políticas públicas e desigualdade social no Recife, 1900-1940

Mais de meio século após o preconceito racial ter se tornado o principal alvo dos movimentos urbanos pelos direitos civis nos Estados Unidos e na África do Sul, e décadas depois do surgimento dos movimentos negros contemporâneos no Brasil, o conjunto de ferramentas legislativas criado no Brasil para promover o direito à cidade ainda adere à longa tradição brasileira de silêncio acerca da questão racial. Este artigo propõe iniciar uma exploração das raízes históricas desse fenômeno, remontando ao surgimento do silêncio sobre a questão racial na política urbana do Recife, Brasil, durante a primeira metade do século XX. O Recife foi eé um exemplo paradigmático do processo pelo qual uma cidade amplamente marcada por traços negros e africanos chegou a ser definida política e legalmente como um espaço pobre, subdesenvolvido e racialmente neutro, onde as desigualdades sociais originaram na exclusão capitalista, e não na escravidão e nas ideologias do racismo científico. Neste sentido, Recife lança luzes sobre a política urbana que se gerou sob a sombra do silêncio racial.More than half a century after racial prejudice became central to urban civil rights movements in the United States and South Africa, and decades after the emergence of Brazil’s contemporary Black movements, Brazil's internationally recognized body of rights-to-the-city legislation still adheres to the country's long historical tradition of racial silence. This article explores the historical roots of this phenomenon by focusing on the emergence of racial silence in Recife, Brazil during the first half of the 20th Century. Recife was and remains a paradigmatic example of the process through which a city marked by its Black and African roots came to be legally and politically defined as a poor, underdeveloped and racially neutral space, where social inequalities derived from capitalist exclusion rather than from slavery and scientific racism. As such, Recife'sexperience sheds light on the urban policies that were generated in the shadow of racial silence

Network architecture and regulatory logic in neural crest development

The neural crest is an ectodermal cell population that gives rise to over 30 cell types during vertebrate embryogenesis. These stem cells are formed at the border of the developing central nervous system and undergo extensive migration before differentiating into components of multiple tissues and organs. Neural crest formation and differentiation is a multistep process, as these cells transition through sequential regulatory states before adopting their adult phenotype. Such changes are governed by a complex gene regulatory network (GRN) that integrates environmental and cell‐intrinsic inputs to regulate cell identity. Studies of neural crest cells in a variety of vertebrate models have elucidated the function and regulation of dozens of the molecular players that are part of this network. The neural crest GRN has served as a platform to explore the molecular control of multipotency, cell differentiation, and the evolution of vertebrates. In this review, we employ this genetic program as a stepping‐stone to explore the architecture and the regulatory principles of developmental GRNs. We also discuss how modern genomic approaches can further expand our understanding of genetic networks in this system and others

Phorbol ester responsiveness of murine Ly-1-lineage B cells from normal and viable motheaten mutant mice.

Simultaneous analysis of stimulated cells for surface phenotype and DNA content by flow cytometry was used to delineate the characteristics of murine lymphocytes that respond to phorbol esters. Peritoneal cells that expressed high-density sIgM, Ly-1, Mac-1 and high-density Pgp-1, were preferentially stimulated to enter the S + G2/M phases of the cell cycle by the protein kinase C agonist, phorbol 12-myristate 13-acetate (PMA). Since these phenotypic characteristics correspond well with those of Ly-1-lineage B cells, non-peritoneal sources of Ly-1+ B cells were examined to test the relative role of lineage and environment in determining phorbol ester responsiveness. Splenic sIgM+ lymphocytes from adult mev/mev mice, and Ly-1+ splenic B cells from neonatal normal mice, were stimulated to enter the S + G2/M phases by PMA, although not to the same extent as peritoneal Ly-1+ B cells. These results suggest that responsiveness to phorbol ester, acting alone, is characteristic of murine Ly-1-lineage B cells regardless of tissue of origin; however, a role for environmental influences has not been completely ruled out