Alteração do Transporte de Ácido Úrico na Glicosúria Renal Familiar e Expressão de SGLT2 no Rim Normal e Patológico

Familial renal glucosuria (FRG) is a rare co -dominantly inherited benign phenotype characterized by the presence of glucose in the urine. It is caused by mutations in the SLC5A2 gene that encodes SGLT2, a Na+ -glucose co -transporter. The purpose of our current work was twofold: to characterize the molecular and phenotype findings of an FRG cohort and, in addition, to detail the SGLT2 expression in the adult human kidney. The phenotype of FRG pedigrees was evaluated using direct sequencing for the identification of sequence variations in the SLC5A2 gene. The expression of SGLT2 in the adult human kidney was studied by immunofluorescence on kidney biopsy specimens. In the absence of renal biopsies from FRG individuals, and in order to evaluate the potential disruption of SGLT2 expression in a glucosuric nephropathy, we have selected cases of nucleoside analogues induced proximal tubular toxicity. We identified six novel SLC5A2 mutations in six FRG pedigrees and described the occurrence of hyperuricosuria associated with hypouricaemia in the two probands with the most severe phenotypes. Histopathological studies proved that SGLT2 is localized to the brush -border of the proximal tubular epithelia cell and that this normal pattern was found to be disrupted in cases of nucleoside analogues induced tubulopathy. We present six novel SLC5A2 mutations, further contributing to the allelic heterogeneity in FRG, and identified hyperuricosuria and hypouricaemia as part of the FRG phenotype. SGLT2 is localized to the brush -border of the proximal tubule in the adult human normal kidney, and aberrant expression of the co -transporter may underlie the glucosuria seen with the use of nucleoside analogues

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

\u201cTime-dependent optimization of a large size hydrogen generation plant using \u201cspilled\u201d water at Itaipu 14 GW hydraulic plant\u201d

In this paper hydrogen generation and storage systems optimization, related to a very large size hydraulic plant (Itaipu, 14 GW) in South America, is investigated using an original multilevel thermo-economic optimization approach developed by the Authors. Hydrogen is produced by water electrolysis employing time-dependent hydraulic energy related to the water which is not normally used by the plant, named \u201cspilled water\u201d. From a thermo-economic point of view, the two main aspects of the study are the optimal definition of the plant size and the whole system management. Both of them are strongly influenced by (i) spilled water energy variability related to its time-dependent distribution during the whole year, (ii) time-dependent electricity demand of Paraguay and Brazil (the owners of the Itaipu plant) electrical grids, and (iii) the hydrogen demand profile. The system analyzed here consists of a very large size hydrogen generation plant (hundreds of MW) based on pressurised water electrolysers fed with the so called \u201cspilled water electricity\u201d, the related H2 storage, and the H2 demand profile for Paraguay transport sector utilization. Since H2 plant optimal size is strongly correlated to optimal management and viceversa, in this paper two hierarchical levels have been considered hour by hour on a complete year time period, in order to minimize capital and variable costs. This time period analysis is necessary to properly take into account spilled energy variability to find out H2 production system optimal size, optimal storage solution and best economical results. For the optimal storage size, two different solutions have been carefully investigated: (i) classical long time H2 physical storage using pressurised tanks at 200 bar; (ii) hybrid one using reduced size physical storage (one day time demand) where the energy to feed electrolysers is taken from electrical grid when spilled water energy is not available [Rivarolo M, Bogarin J, Magistri L, Massardo AF. Hydrogen generation with large size renewable plants: the Itaipu 14 GW hydraulic plant case. In: 3rd international conference of applied energy (ICAE), 16e18 May 2011, Perugia; 2011.]. For both the two solutions, timedependent results are presented and discussed with particular emphasis to economic aspects, system size, capital costs and related investments. It is worthy to note that the results reported here for this particular H2 large size plant case represent a general methodology, since it is applicable to different size, primary renewable energy, plant location, and different H2 utilization

A comparative analysis of island floras challenges taxonomy-based biogeographical models of speciation

Speciation on islands, and particularly the divergence of species in situ, has long been debated. Here, we present one of the first, complete assessments of the geographic modes of speciation for the flora of a small oceanic island. Cocos Island (Costa Rica) is pristine; it is located 550 km off the Pacific coast of Central America. It harbors 189 native plant species, 33 of which are endemic. Using phylogenetic data from insular and mainland congeneric species, we show that all of the endemic species are derived from independent colonization events rather than in situ speciation. This is in sharp contrast to the results of a study carried out in a comparable system, Lord Howe Island (Australia), where as much as 8.2% of the plant species were the product of sympatric speciation. Differences in physiography and age between the islands may be responsible for the contrasting patterns of speciation observed. Importantly, comparing phylogenetic assessments of the modes of speciation with taxonomy-based measures shows that widely used island biogeography approaches overestimate rates of in situ speciation

Pollination of Habenaria tridactylites on the Canary Islands

We investigated the pollination of Habenaria tridactylites, an endemic orchid of the Canary Islands. The entirely green, widely open flowers have a long spur containing nectar. We carried out fieldwork, a molecular clock analysis, herbarium surveys, identified pollinators by both morphology and DNA barcoding, and measured the length of floral spurs and insect tongues using a combination of traditional and innovative micro‐CT scanning methods to 1) determine the pollinator of this orchid and 2) investigate correlations between local mean spur length and age, altitude and longitude of the island. Habenaria tridactylites was found to be pollinated on Tenerife by both small and intermediate sized moth species with variable tongue lengths and mostly belonging to Geometridae and to a lesser extent Crambidae, Erebidae, Noctuidae and Tortricidae. Of the sixteen moth species identified, nine are endemic to the Canary Islands or Macaronesia. The different local populations of H. tridactylites on the islands of Gran Canaria, El Hierro, La Gomera, La Palma and Tenerife with different ages and distances from mainland Africa, did not show a significant correlation of mean spur length and altitude, but did show a significant and positive linear correlation with longitude and the geological age of the island. The latter is congruent with the evolutionary arms race theory first proposed by Darwin, suggesting that flowers gradually evolve longer spurs and pollinators longer tongues

Pollination of Habenaria tridactylites on the Canary Islands

We investigated the pollination of Habenaria tridactylites, an endemic orchid of the Canary Islands. The entirely green, widely open flowers have a long spur containing nectar. We carried out fieldwork, a molecular clock analysis, herbarium surveys, identified pollinators by both morphology and DNA barcoding, and measured the length of floral spurs and insect tongues using a combination of traditional and innovative micro‐CT scanning methods to 1) determine the pollinator of this orchid and 2) investigate correlations between local mean spur length and age, altitude and longitude of the island. Habenaria tridactylites was found to be pollinated on Tenerife by both small and intermediate sized moth species with variable tongue lengths and mostly belonging to Geometridae and to a lesser extent Crambidae, Erebidae, Noctuidae and Tortricidae. Of the sixteen moth species identified, nine are endemic to the Canary Islands or Macaronesia. The different local populations of H. tridactylites on the islands of Gran Canaria, El Hierro, La Gomera, La Palma and Tenerife with different ages and distances from mainland Africa, did not show a significant correlation of mean spur length and altitude, but did show a significant and positive linear correlation with longitude and the geological age of the island. The latter is congruent with the evolutionary arms race theory first proposed by Darwin, suggesting that flowers gradually evolve longer spurs and pollinators longer tongues

Radiation arteriopathy in the transgenic arteriovenous fistula model

Objective: The transgenic arteriovenous fistula model, surgically constructed with transgenic mouse aorta interposed in common carotid artery-to-external jugular vein fistulae in nude rats, has a 4-month experimental window because patency and transgenic phenotype are lost over time. We adapted this model to investigate occlusive arteriopathy in brain arteriovenous malformations after radiosurgery by radiating grafted aorta before insertion in the fistula. We hypothesized that high-dose radiation would reproduce the arteriopathy observed clinically within the experimental time window and that deletions of endoglin (ENG) and endothelial nitric oxide synthase (eNOS) genes would modify the radiation response. METHODS: Radiation arteriopathy in the common carotid arteries of 171 wild-type mice was examined with doses of 25, 80, 120, or 200 Gy (Experiment 1). Radiation arteriopathy in 68 wild-type arteriovenous fistulae was examined histologically and morphometrically with preoperative radiation doses of 0, 25, or 200 Gy (Experiment 2). Radiation arteriopathy in 51 transgenic arteriovenous fistulae (36 ENG and 15 eNOS knock-out fistulae) was examined using preoperative radiation doses of 0, 25, or 200 Gy (Experiment 3). RESULTS: High-dose radiation (200 Gy) of mouse common carotid arteries induced only mild arteriopathy (mean score, 0.66) without intimal hyperplasia and with high mortality (68%). Radiation arteriopathy in wild-type arteriovenous fistulae was severe (mean score, 3.5 at 200 Gy), with intimal hyperplasia and medial disruption at 3 months, decreasing luminal areas with increasing dose, and no mortality. Arteriopathy was robust in transgenic arteriovenous fistulae with ENG +/- and with eNOS +/-, with thick intimal hyperplasia in the former and distinct smooth muscle cell proliferation in the latter. CONCLUSION: The transgenic arteriovenous fistula model can be adapted to rapidly reproduce radiation arteriopathy observed in resected brain arteriovenous malformations after radiosurgery. High radiation doses accelerate the progression of arteriopathy to fit the 4-month time limitation of the model, allowing transgenic tissues to retain their phenotypes throughout the experimental window. Modified radiation responses in ENG and eNOS knock-out fistulae indicate that arteriopathy after arteriovenous malformation radiosurgery might potentially be enhanced by altered gene expression

DNA barcoding the floras of biodiversity hotspots

DNA barcoding is a technique in which species identification is performed by using DNA sequences from a small fragment of the genome, with the aim of contributing to a wide range of ecological and conservation studies in which traditional taxonomic identification is not practical. DNA barcoding is well established in animals, but there is not yet any universally accepted barcode for plants. Here, we undertook intensive field collections in two biodiversity hotspots (Mesoamerica and southern Africa). Using >1,600 samples, we compared eight potential barcodes. Going beyond previous plant studies, we assessed to what extent a “DNA barcoding gap” is present between intra- and interspecific variations, using multiple accessions per species. Given its adequate rate of variation, easy amplification, and alignment, we identified a portion of the plastid matK gene as a universal DNA barcode for flowering plants. Critically, we further demonstrate the applicability of DNA barcoding for biodiversity inventories. In addition, analyzing >1,000 species of Mesoamerican orchids, DNA barcoding with matK alone reveals cryptic species and proves useful in identifying species listed in Convention on International Trade of Endangered Species (CITES) appendixes