Optimizing dialysis dose in the context of frailty: an exploratory study

Introduction Frailty is a multicausal syndrome characterized by a decrease in strength, resistance and physiological function, which makes the individual vulnerable and dependent, and increases his/her mortality. This syndrome is more prevalent among older individuals, and chronic kidney disease patients, particularly those on dialysis. Dialysis dose is currently standardized for hemodialysis (HD) patients regardless of their age and functional status. However, it has been postulated that the dialysis dose required in older patients, especially frail ones, should be lower, since it could increase their degree of frailty. Then, the purpose of this study was to evaluate if there would be a correlation between the dose of Kt/V and the degree of frailty in a population of adult patients on HD. Materials and methods A cross-sectional study with 82 patients on HD in Barranquilla (Colombia) and Lobos (Argentina) was conducted. Socio-demographic and laboratory data, as well as dialysis doses (Kt/V) were recorded and scales of fragility, physical activity, gait and grip strength were applied. Then these data were correlated by a Spearman’s correlation and a logistic regression. Results CFS, social isolation, physical activity, gait speed, and prehensile strength tests were outside the reference ranges in the studied group. No significant correlation was found between dialysis dose and all the above mentioned functional tests. However, a significant and inverse correlation between physical activity and CFS was documented (score − 1.41 (CI − 2.1 to − 0.7). Conclusion No significant correlation was documented between Kt/V value and different parameters of the frailty status, but this status correlated significantly and inversely with physical activity in this group. Frailty status in hemodialysis patients was significantly higher in older individuals, although young individuals were not exempt from it

A roadmap for amphibious drilling at the Campi Flegrei caldera: insights from a MagellanPlus workshop

Large calderas are among the Earth's major volcanic features. They are associated with large magma reservoirs and elevated geothermal gradients. Caldera-forming eruptions result from the withdrawal and collapse of the magma chambers and produce large-volume pyroclastic deposits and later-stage deformation related to post-caldera resurgence and volcanism. Unrest episodes are not always followed by an eruption; however, every eruption is preceded by unrest. The Campi Flegrei caldera (CFc), located along the eastern Tyrrhenian coastline in southern Italy, is close to the densely populated area of Naples. It is one of the most dangerous volcanoes on Earth and represents a key example of an active, resurgent caldera. It has been traditionally interpreted as a nested caldera formed by collapses during the 100–200 km3 Campanian Ignimbrite (CI) eruption at ∼39 ka and the 40 km3 eruption of the Neapolitan Yellow Tuff (NYT) at ∼15 ka. Recent studies have suggested that the CI may instead have been fed by a fissure eruption from the Campanian Plain, north of Campi Flegrei. A MagellanPlus workshop was held in Naples, Italy, on 25–28 February 2017 to explore the potential of the CFc as target for an amphibious drilling project within the International Ocean Discovery Program (IODP) and the International Continental Drilling Program (ICDP). It was agreed that Campi Flegrei is an ideal site to investigate the mechanisms of caldera formation and associated post-caldera dynamics and to analyze the still poorly understood interplay between hydrothermal and magmatic processes. A coordinated onshore–offshore drilling strategy has been developed to reconstruct the structure and evolution of Campi Flegrei and to investigate volcanic precursors by examining (a) the succession of volcanic and hydrothermal products and related processes, (b) the inner structure of the caldera resurgence, (c) the physical, chemical, and biological characteristics of the hydrothermal system and offshore sediments, and (d) the geological expression of the phreatic and hydromagmatic eruptions, hydrothermal degassing, sedimentary structures, and other records of these phenomena. The deployment of a multiparametric in situ monitoring system at depth will enable near-real-time tracking of changes in the magma reservoir and hydrothermal system

Arc and forearc rifting in the Tyrrhenian subduction system

The evolution of forearc and backarc domains is usually treated separately, as they are separated by a volcanic arc. We analyse their spatial and temporal relationships in the Tyrrhenian subduction system, using seismic profiles and numerical modelling. A volcanic arc, which included the Marsili volcano, was involved in arc-rifting during the Pliocene. This process led to the formation of an oceanic backarc basin (~ 1.8 Ma) to the west of the Marsili volcano. The eastern region corresponded to the forearc domain, floored by serpentinised mantle. Here, a new volcanic arc formed at ~ 1 Ma, marking the onset of the forearc-rifting. This work highlights that fluids and melts induce weakening of the volcanic arc region and drive the arc-rifting that led to the backarc basin formation. Later, the slab rollback causes the trench-ward migration of volcanism that led to the forearc- rifting under the control of fluids released from the downgoing plate.ISSN:2045-232

Clinical expression of familial hypercholesterolemia in clusters of mutations of the LDL receptor gene that cause a receptor-defective or receptor-negative phenotype

Seventy-one mutations of the low density lipoprotein (LDL) receptor gene were identified in 282 unrelated Italian familial hypercholesterolemia (FH) heterozygotes. By extending genotype analysis to families of the index cases, we identified 12 mutation clusters and localized them in specific areas of Italy. To evaluate the impact of these mutations on the clinical expression of FH, the clusters were separated into 2 groups: receptor-defective and receptor-negative, according to the LDL receptor defect caused by each mutation. These 2 groups were comparable in terms of the patients’ age, sex distribution, body mass index, arterial hypertension, and smoking status. In receptor-negative subjects, LDL cholesterol was higher (118%) and high density lipoprotein cholesterol lower (25%) than the values found in receptor-defective subjects. The prevalence of tendon xanthomas and coronary artery disease (CAD) was 2-fold higher in receptor-negative subjects. In patients >30 years of age in both groups, the presence of CAD was related to age, arterial hypertension, previous smoking, and LDL cholesterol level. Independent contributors to CAD in the receptor-defective subjects were male sex, arterial hypertension, and LDL cholesterol level; in the receptor-negative subjects, the first 2 variables were strong predictors of CAD, whereas the LDL cholesterol level had a lower impact than in receptor-defective subjects. Overall, in receptor-negative subjects, the risk of CAD was 2.6-fold that of receptordefective subjects. Wide interindividual variability in LDL cholesterol levels was found in each cluster. Apolipoprotein E genotype analysis showed a lowering effect of the ε2 allele and a raising effect of the ε4 allele on the LDL cholesterol level in both groups; however, the apolipoprotein E genotype accounted for only 4% of the variation in LDL cholesterol. Haplotype analysis showed that all families of the major clusters shared the same intragenic haplotype cosegregating with the mutation, thus suggesting the presence of common ancestors

A roadmap for amphibious drilling at the Campi Flegrei caldera: insights from a MagellanPlus workshop

Large calderas are among the Earth’s major volcanic features. They are associated with large magma reservoirs and elevated geothermal gradients. Caldera-forming eruptions result from the withdrawal and collapse of the magma chambers and produce large-volume pyroclastic deposits and later-stage deformation related to post-caldera resurgence and volcanism. Unrest episodes are not always followed by an eruption; however, every eruption is preceded by unrest. The Campi Flegrei caldera (CFc), located along the eastern Tyrrhenian coastline in southern Italy, is close to the densely populated area of Naples. It is one of the most dangerous volcanoes on Earth and represents a key example of an active, resurgent caldera. It has been traditionally interpreted as a nested caldera formed by collapses during the 100–200 km 3 Campanian Ignimbrite (CI) eruption at ∼ 39 ka and the 40 km 3 eruption of the Neapolitan Yellow Tuff (NYT) at ∼ 15 ka. Recent studies have suggested that the CI may instead have been fed by a fissure eruption from the Campanian Plain, north of Campi Flegrei. A MagellanPlus workshop was held in Naples, Italy, on 25–28 February 2017 to explore the potential of the CFc as target for an amphibious drilling project within the International Ocean Discovery Program (IODP) and the International Continental Drilling Program (ICDP). It was agreed that Campi Flegrei is an ideal site to investigate the mechanisms of caldera formation and associated post-caldera dynamics and to analyze the still poorly understood interplay between hydrothermal and magmatic processes. A coordinated onshore–offshore drilling strategy has been developed to reconstruct the structure and evolution of Campi Flegrei and to investigate volcanic precursors by examining (a) the succession of volcanic and hydrothermal products and related processes, (b) the inner structure of the caldera resurgence, (c) the physical, chemical, and biological characteristics of the hydrothermal system and offshore sediments, and (d) the geological expression of the phreatic and hydromagmatic eruptions, hydrothermal degassing, sedimentary structures, and other records of these phenomena. The deployment of a multiparametric in situ monitoring system at depth will enable near-real-time tracking of changes in the magma reservoir and hydrothermal system

Thymic atrophy in cattle poisoned with Solanum glaucophyllum Atrofia do timo em bovinos intoxicados por Solanum glaucophyllum

Solanum glaucophyllum (Sg) [= S. malacoxylon] is a calcinogenic plant inducing "Enzootic Calcinosis" in cattle. The 1,25-dihydroxyvitamin D3, its main toxic principle, regulates bone and calcium metabolism and also exerts immunomodulatory effects. Thymocyte precursors from bone marrow-derived progenitor cells differentiate into mature T-cells. Differentiation of most T lymphocytes is characterized not only by the variable expression of CD4/CD8 receptor molecules and increased surface density of the T cell antigen receptor, but also by changes in the glycosylation pattern of cell surface glycolipids or glycoproteins. Thymocytes exert a feedback influence on thymic non-lymphoid cells. Sg-induced modifications on cattle thymus T-lymphocytes and on non-lymphoid cells were analysed. Heifers were divided into 5 groups (control, intoxicated with Sg during 15, 30 or 60 days, and probably recovered group). Histochemical, immunohistochemical, lectinhistochemical and morphometric techniques were used to characterize different cell populations of the experimental heifers. Sg-poisoned heifers showed a progressive cortical atrophy that was characterized using the peanut agglutinin (PNA) lectin that recognizes immature thymocytes. These animals also increased the amount of non-lymphoid cells per unit area detected with the Picrosirius technique, WGA and DBA lectins, and pancytokeratin and S-100 antibodies. The thymus atrophy found in intoxicated animals resembled that of the physiological aging process. A reversal effect on these changes was observed after suppression of the intoxication. These findings suggest that Sg-intoxication induces either directly, through the 1,25-dihydroxyvitamin D3 itself, or indirectly through the hypercalcemia, the observed alteration of the thymus.<br>Solanum glaucophyllum (Sg) [= S. malacoxylon] é uma planta calcinogênica que induz "Calcinose Enzoótica" em bovinos. O 1,25-dihidroxivitamina D3, seu principal agente tóxico, regula o metabolismo ósseo, o metabolismo de cálcio e também mostra efeitos na imunomodulação. Precursores de timócitos derivados da medula óssea se diferenciam em linfócitos T maduros. A diferenciação da maioria dos linfócitos T é caracterizada pela expressão variável de moléculas de receptores CD4/CD8 e densidade aumentada dos receptores antigênicos de superfície de células T. Alem disso, há mudanças no padrão de glicosilação de glicolipídeos na superfície celular ou de glicoproteínas. Timócitos mostram uma influência de retro alimentação em células tímicas não-linfóides. Foram analisadas modificações induzidas pelo Sg em linfócitos T e células tímicas não-linfóides de bovinos. Novilhas foram divididas em 5 grupos (controle, intoxicadas com Sg durante 15, 30 ou 60 dias, e grupo provavelmente recuperado). As diferentes populações celulares das novilhas experimentais foram caracterizadas com técnicas histoquímicas, imuno-histoquímicas, lectina-histoquímicas e morfométricas. As novilhas intoxicadas com Sg mostraram uma atrofia cortical progressiva que foi caracterizada usando a lectina aglutinina de amendoim (PNA) que reconhece timócitos imaturos. Estes animais também aumentaram as células não-linfóides tímicas por unidade de área, detectadas com a técnica de Picrosirius, lectinas WGA e DBA e anticorpos antipancitoqueratina e anti-S-100. A atrofia de timo observada nos animais intoxicados foi semelhante àquela do processo de envelhecimento fisiológico. Após supressão da intoxicação, foi observado um efeito de reversão nestas mudanças. Estes resultados sugerem que a intoxicação por Sg induza a alteração observada no timo diretamente, pela ação de 1,25-dihidroxivitamina D3, ou indiretamente, pela ação da hipercalcemia