Effect of serum phosphate on parathyroid hormone secretion during hemodialysis

Effect of serum phosphate on parathyroid hormone secretion during hemodialysis.BackgroundRecent studies have demonstrated that a high concentration of phosphate directly stimulates parathyroid hormone (PTH) secretion. High serum levels of phosphate are usually observed in patients with end-stage renal disease. The aim of the present study was to evaluate whether serum phosphate concentration had an acute effect on PTH secretion in hemodialysis patients. The levels of serum phosphate were manipulated during the hemodialysis session by using a phosphate free dialysate or a dialysate with a high content of phosphate.MethodsTen stable hemodialysis patients with PTH values above 300 pg/ml were included in the study. A PTH-calcium curve was obtained during both high phosphate and phosphate free hemodialysis.ResultsThe serum phosphate concentration remained high (2.17 ± 0.18mM) throughout the high phosphate hemodialysis and decreased progressively to normal levels (1.02 ± 0.06mM) during the phosphate free hemodialysis. The serum PTH levels at maximal inhibition by hypercalcemia (minimal PTH) were greater during the high phosphate than the phosphate free hemodialysis (413 ± 79 vs. 318 ± 76 pg/ml, P < 0.003). In all patients the values of minimum PTH were greater during the high phosphorus than the phosphorus free hemodialysis. The values of maximally stimulated PTH during hypocalcemia and the set point of the PTH-calcium curve were similar during the high phosphate and the phosphate free hemodialysis.ConclusionThe maintenance of high serum phosphorus levels during hemodialysis prevented, in part, the inhibition of PTH secretion by calcium, which strongly suggests that in hemodialysis patients high serum phosphate contributes directly to the elevation of PTH levels despite normal or high serum calcium concentration

Genetic deficiency or pharmacological inhibition of miR-33 protects from kidney fibrosis

Previous work has reported the important links between cellular bioenergetics and the development of chronic kidney disease, highlighting the potential for targeting metabolic functions to regulate disease progression. More recently, it has been shown that alterations in fatty acid oxidation (FAO) can have an important impact on the progression of kidney disease. In this work, we demonstrate that loss of miR-33, an important regulator of lipid metabolism, can partially prevent the repression of FAO in fibrotic kidneys and reduce lipid accumulation. These changes were associated with a dramatic reduction in the extent of fibrosis induced in 2 mouse models of kidney disease. These effects were not related to changes in circulating leukocytes because bone marrow transplants from miR-33–deficient animals did not have a similar impact on disease progression. Most important, targeted delivery of miR-33 peptide nucleic acid inhibitors to the kidney and other acidic microenvironments was accomplished using pH low insertion peptides as a carrier. This was effective at both increasing the expression of factors involved in FAO and reducing the development of fibrosis. Together, these findings suggest that miR-33 may be an attractive therapeutic target for the treatment of chronic kidney disease

Congenital leptin deficiency and leptin gene missense mutation found in two colombian sisters with severe obesity

Background: Congenital leptin deficiency is a recessive genetic disorder associated with severe early-onset obesity. It is caused by mutations in the leptin (LEP) gene, which encodes the protein product leptin. These mutations may cause nonsense-mediated mRNA decay, defective secretion or the phenomenon of biologically inactive leptin, but typically lead to an absence of circulating leptin, resulting in a rare type of monogenic extreme obesity with intense hyperphagia, and serious metabolic abnormalities. Methods: We present two severely obese sisters from Colombia, members of the same lineal consanguinity. Their serum leptin was measured by MicroELISA. DNA sequencing was performed on MiSeq equipment (Illumina) of a next-generation sequencing (NGS) panel involving genes related to severe obesity, including LEP. Results: Direct sequencing of the coding region of LEP gene in the sisters revealed a novel homozygous missense mutation in exon 3 [NM_002303.3], C350G>T [p.C117F]. Detailed information and clinical measurements of these sisters were also collected. Their serum leptin levels were undetectable despite their markedly elevated fat mass. Conclusions: The mutation of LEP, absence of detectable leptin, and the severe obesity found in these sisters provide the first evidence of monogenic leptin deficiency reported in the continents of North and South America. © 2019 by the authors. Licensee MDPI, Basel, Switzerland

CC8 MRSA Strains Harboring SCCmec Type IVc are Predominant in Colombian Hospitals

BACKGROUND: Recent reports highlight the incursion of community-associated MRSA within healthcare settings. However, knowledge of this phenomenon remains limited in Latin America. The aim of this study was to evaluate the molecular epidemiology of MRSA in three tertiary-care hospitals in Medellín, Colombia. METHODS: An observational cross-sectional study was conducted from 2008-2010. MRSA infections were classified as either community-associated (CA-MRSA) or healthcare-associated (HA-MRSA), with HA-MRSA further classified as hospital-onset (HAHO-MRSA) or community-onset (HACO-MRSA) according to standard epidemiological definitions established by the U.S. Centers for Disease Control and Prevention (CDC). Genotypic analysis included SCCmec typing, spa typing, PFGE and MLST. RESULTS: Out of 538 total MRSA isolates, 68 (12.6%) were defined as CA-MRSA, 243 (45.2%) as HACO-MRSA and 227 (42.2%) as HAHO-MRSA. The majority harbored SCCmec type IVc (306, 58.7%), followed by SCCmec type I (174, 33.4%). The prevalence of type IVc among CA-, HACO- and HAHO-MRSA isolates was 92.4%, 65.1% and 43.6%, respectively. From 2008 to 2010, the prevalence of type IVc-bearing strains increased significantly, from 50.0% to 68.2% (p = 0.004). Strains harboring SCCmec IVc were mainly associated with spa types t1610, t008 and t024 (MLST clonal complex 8), while PFGE confirmed that the t008 and t1610 strains were closely related to the USA300-0114 CA-MRSA clone. Notably, strains belonging to these three spa types exhibited high levels of tetracycline resistance (45.9%). CONCLUSION: CC8 MRSA strains harboring SCCmec type IVc are becoming predominant in Medellín hospitals, displacing previously reported CC5 HA-MRSA clones. Based on shared characteristics including SCCmec IVc, absence of the ACME element and tetracycline resistance, the USA300-related isolates in this study are most likely related to USA300-LV, the recently-described 'Latin American variant' of USA300

Infectious Diseases, Social, Economic and Political Crises, Anthropogenic Disasters and Beyond: Venezuela 2019 – Implications for Public Health and Travel Medicine

During last months, there have been a significant increase in the evidences showing the catastrophic health situation in Venezuela. There are multiple epidemics, increase in emerging and reemerging infectious, tropical and parasitic diseases as consequences of the social, economic and political crises, which would be considered today a clearly anthropogenic disaster. Venezuela is facing in 2019, the worse sanitary conditions, with multiple implications for public health and travel medicine. So far, from a global perspective, this situation will be an impediment for the achievement of the sustainable development goals (SDG) in 2030. In this multiauthor review, there is a comprehensive analysis of the situation for infectious diseases, non-communicable diseases, their impact in the Americas region, given the migration crisis as well as the comparative status of the SDG 2030. This discussion can provide input for prioritizing emerging health problems and establish a future agenda

Infectious Diseases, Social, Economic and Political Crises, Anthropogenic Disasters and Beyond: Venezuela 2019 – Implications for Public Health and Travel Medicine

During last months, there have been a significant increase in the evidences showing the catastrophic health situation in Venezuela. There are multiple epidemics, increase in emerging and reemerging infectious, tropical and parasitic diseases as consequences of the social, economic and political crises, which would be considered today a clearly anthropogenic disaster. Venezuela is facing in 2019, the worse sanitary conditions, with multiple implications for public health and travel medicine. So far, from a global perspective, this situation will be an impediment for the achievement of the sustainable development goals (SDG) in 2030. In this multiauthor review, there is a comprehensive analysis of the situation for infectious diseases, non-communicable diseases, their impact in the Americas region, given the migration crisis as well as the comparative status of the SDG 2030. This discussion can provide input for prioritizing emerging health problems and establish a future agenda

A Self-Organized ECM-Mimetic Model Based on an Amphiphilic Multiblock Silk-Elastin-Like co-Recombinamer with a Concomitant Dual Physical Gelation Process

Although significant progress has been made in the area of injectable hydrogels for biomedical applications and model cell niches, further improvements are still needed, especially in terms of mechanical performance, stability, and biomimicry of the native fibrillar architecture found in the extracellular matrix (ECM). This work focuses on the design and production of a silk-elastin-based injectable multiblock corecombinamer that spontaneously forms a stable physical nanofibrillar hydrogel under physiological conditions. That differs from previously reported silk-elastin-like polymers on a major content and predominance of the elastin-like part, as well as a more complex structure and behavior of such a part of the molecule, which is aimed to obtain well-defined hydrogels. Rheological and DSC experiments showed that this system displays a coordinated and concomitant dual gelation mechanism. In a first stage, a rapid, thermally driven gelation of the corecombinamer solution takes place once the system reaches body temperature due to the thermal responsiveness of the elastin-like (EL) parts and the amphiphilic multiblock design of the corecombinamer. A bridged micellar structure is the dominant microscopic feature of this stage, as demonstrated by AFM and TEM. Completion of the initial stage triggers the second, which is comprised of a stabilization, reinforcement, and microstructuring of the gel. FTIR analysis shows that these events involve the formation of β-sheets around the silk motifs. The emergence of such β-sheet structures leads to the spontaneous self-organization of the gel into the final fibrous structure. Despite the absence of biological cues, here we set the basis of the minimal structure that is able to display such a set of physical properties and undergo microscopic transformation from a solution to a fibrous hydrogel. The results point to the potential of this system as a basis for the development of injectable fibrillar biomaterial platforms toward a fully functional, biomimetic, artificial extracellular matrix, and cell niches.Este trabajo forma parte de Proyectos de Investigación financiados por la Comisión Europea a través del Fondo Europeo de Desarrollo Regional (ERDF), por el del MINECO (MAT2013-41723-R, MAT2013- 42473-R, PRI-PIBAR-2011-1403 y MAT2012-38043), la Junta de Castilla y León (VA049A11, VA152A12 y VA155A12) y el Instituto de Salud Carlos III bajo el Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León

Multi-ancestry GWAS reveals excitotoxicity associated with outcome after ischaemic stroke

During the first hours after stroke onset, neurological deficits can be highly unstable: some patients rapidly improve, while others deteriorate. This early neurological instability has a major impact on long-term outcome. Here, we aimed to determine the genetic architecture of early neurological instability measured by the difference between the National Institutes of Health Stroke Scale (NIHSS) within 6 h of stroke onset and NIHSS at 24 h. A total of 5876 individuals from seven countries (Spain, Finland, Poland, USA, Costa Rica, Mexico and Korea) were studied using a multi-ancestry meta-analyses. We found that 8.7% of NIHSS at 24 h of variance was explained by common genetic variations, and also that early neurological instability has a different genetic architecture from that of stroke risk. Eight loci (1p21.1, 1q42.2, 2p25.1, 2q31.2, 2q33.3, 5q33.2, 7p21.2 and 13q31.1) were genome-wide significant and explained 1.8% of the variability suggesting that additional variants influence early change in neurological deficits. We used functional genomics and bioinformatic annotation to identify the genes driving the association from each locus. Expression quantitative trait loci mapping and summary data-based Mendelian randomization indicate that ADAM23 (log Bayes factor = 5.41) was driving the association for 2q33.3. Gene-based analyses suggested that GRIA1 (log Bayes factor = 5.19), which is predominantly expressed in the brain, is the gene driving the association for the 5q33.2 locus. These analyses also nominated GNPAT (log Bayes factor = 7.64) ABCB5 (log Bayes factor = 5.97) for the 1p21.1 and 7p21.1 loci. Human brain single-nuclei RNA-sequencing indicates that the gene expression of ADAM23 and GRIA1 is enriched in neurons. ADAM23, a presynaptic protein and GRIA1, a protein subunit of the AMPA receptor, are part of a synaptic protein complex that modulates neuronal excitability. These data provide the first genetic evidence in humans that excitotoxicity may contribute to early neurological instability after acute ischaemic stroke. Ibanez et al. perform a multi-ancestry meta-analysis to investigate the genetic architecture of early stroke outcomes. Two of the eight genome-wide significant loci identified-ADAM23 and GRIA1-are involved in synaptic excitability, suggesting that excitotoxicity contributes to neurological instability after ischaemic stroke.Peer reviewe

Preface paper to the Semi-Arid Land-Surface-Atmosphere (SALSA) Program special issue

The Semi-Arid Land-Surface-Atmosphere Program (SALSA) is a multi-agency, multi-national research effort that seeks to evaluate the consequences of natural and human-induced environmental change in semi-arid regions. The ultimate goal of SALSA is to advance scientific understanding of the semi-arid portion of the hydrosphere–biosphere interface in order to provide reliable information for environmental decision making. SALSA approaches this goal through a program of long-term, integrated observations, process research, modeling, assessment, and information management that is sustained by cooperation among scientists and information users. In this preface to the SALSA special issue, general program background information and the critical nature of semi-arid regions is presented. A brief description of the Upper San Pedro River Basin, the initial location for focused SALSA research follows. Several overarching research objectives under which much of the interdisciplinary research contained in the special issue was undertaken are discussed. Principal methods, primary research sites and data collection used by numerous investigators during 1997–1999 are then presented. Scientists from about 20 US, five European (four French and one Dutch), and three Mexican agencies and institutions have collaborated closely to make the research leading to this special issue a reality. The SALSA Program has served as a model of interagency cooperation by breaking new ground in the approach to large scale interdisciplinary science with relatively limited resources