Fluid management in the perioperative setting: mind the kidney

Acute kidney injury (AKI) is one of the most frequent complications in critically ill patients and in the perioperative setting. The anatomical structure and the microvasculature of the kidney makes it highly vulnerable to hypoxia. Although fluid therapy is considered crucial in situations where improvement of cardiac output is needed, it can also contribute to AKI development when administered inappropriately. Hemodilution and anemia during cardio-pulmonary bypass have been demonstrated to be risk factors for AKI and they are likely to be a consequence of fluid administration. In order to assess the perfusion of the kidneys it is necessary to investigate the determinants of delivery of oxygen at the microcirculatory level. Indeed, fluids can decrease the capillary hematocrit and the functional capillary density, affecting the renal oxygenation and increasing the risk of AKI. Monitoring sublingual microcirculation can be a reliable tool to guide fluid administration, aiming to prevent or improve perioperative AKI

Chorioallantoic and yolk sac placentation in the plains viscacha (Lagostomus maximus) - A caviomorph rodent with natural polyovulation

Objectives: Reproduction in the plains viscacha is characterized by the polyovulation of hundreds of oocytes, the loss of implantation and the development of 1-3 offspring. Our goal was to determine whether placental development was affected by these specializations. Study design: Thirteen placentas from early pregnancy to near-term pregnancy were analyzed using histological, immunohistochemical and transmission electron microscopy. Results: An inverted, villous yolk sac was present. Placentas were formed by the trophospongium, labyrinth and subplacenta. A lobulated structure with a hemomonochorial barrier was established early in pregnancy. Proliferating trophoblast that was clustered at the outer border and inside the labyrinth was responsible for placental growth. Trophoblast invasion resulted from the cellular trophoblast and syncytial streamers derived from the subplacenta. Different from other caviomorphs, numerous giant cells were observed. Conclusions: The principle processes of placentation in caviomorphs follow an extraordinarily stable pattern that is independent of specializations, such as polyovulation.Facultad de Ciencias Veterinaria

Realization and high power test of damped C -band accelerating structures

The linac of the European project Extreme Light Infrastructure-Nuclear Physics (ELI-NP) foresees the use of 12 traveling wave C-band accelerating structures. The cavities are 1.8 m long, quasiconstant gradient, and have a field phase advance per cell of 2π/3. They operate at 100 Hz repetition rate, and, because of the multibunch operation, they have been designed with a dipole higher-order mode (HOM) damping system to avoid beam breakup. The structures have symmetric input and output couplers and integrate, in each cell, a damping system based on silicon carbide (SiC) rf absorbers coupled to each cell through waveguides. An optimization of the electromagnetic and mechanical design has been done to simplify the fabrication and to reduce the costs. The cavities have been fabricated, and the first full-scale prototype has been also successfully tested at the nominal gradient of 33 MV/m, repetition rate of 100 Hz, and pulse length of 820 ns. It represents, to our knowledge, the first full-scale linac structure with HOM damping waveguides and SiC absorbers tested at this high gradient. In the paper, we illustrate the realization process of such a complicated device together with the low and high power test results

The effect of CO₂ laser therapy on vaginal microcirculatory parameters in an animal model for genitourinary syndrome of menopause

Background: Vaginal laser therapy for the treatment of genitourinary syndrome of menopause (GSM) has been introduced to the market with limited (pre)clinical and experimental evidence supporting its efficacy. It is suggested that vaginal laser therapy increases epithelial thickness and improves vascularization, but the underlying biological working mechanism has not been substantiated yet. Objective: To evaluate the effects of CO2 laser therapy on vaginal atrophy using noninvasive incident dark field (IDF) imaging in a large animal model for GSM. Design, Setting, and Participants: An animal study was conducted between 2018 and 2019 and included 25 Dohne Merino ewes, of which 20 underwent bilateral ovariectomy (OVX) to induce iatrogenic menopause, and 5 did not. The total study duration was 10 months. Interventions: Five months after OVX, ovariectomized ewes received monthly applications of CO2 laser (n = 7), vaginal estrogen (n = 7), or no treatment (n = 6) for 3 months. IDF imaging was performed monthly in all animals. Outcome Measurements and Statistical Analysis: The primary outcome was the proportion of image sequences containing capillary loops (angioarchitecture). Secondary outcomes included focal depth (epithelial thickness), and quantitative measures of vessel density and perfusion. Treatment effects were evaluated using ANCOVA and binary logistic regression. Results and Limitations: Compared to OVX-only, ewes treated with estrogen demonstrated a higher capillary loops proportion (4% vs. 75%, p &lt; 0.01), and higher focal depth (60 (IQR 60–80) vs. 80 (IQR 80–80) p &lt; 0.05). CO2 laser therapy did not change microcirculatory parameters. As the ewes' vaginal epithelium is thinner than that of humans, it may demand different laser settings. Conclusions: In a large animal model for GSM, CO2 laser therapy does not affect microcirculatory outcomes related to GSM, whereas vaginal estrogen treatment does. Until more homogeneous and objective evidence about its efficacy is available, CO2 laser therapy should not be adopted into widespread practice for treating GSM.</p

The effect of CO2_{2} laser therapy on vaginal microcirculatory parameters in an animal model for genitourinary syndrome of menopause

Background: Vaginal laser therapy for the treatment of genitourinary syndrome of menopause (GSM) has been introduced to the market with limited (pre)clinical and experimental evidence supporting its efficacy. It is suggested that vaginal laser therapy increases epithelial thickness and improves vascularization, but the underlying biological working mechanism has not been substantiated yet. Objective: To evaluate the effects of CO$_{2}$ laser therapy on vaginal atrophy using noninvasive incident dark field (IDF) imaging in a large animal model for GSM. Design, Setting, and Participants: An animal study was conducted between 2018 and 2019 and included 25 Dohne Merino ewes, of which 20 underwent bilateral ovariectomy (OVX) to induce iatrogenic menopause, and 5 did not. The total study duration was 10 months.InterventionsFive months after OVX, ovariectomized ewes received monthly applications of CO$_{2}$ laser (n = 7), vaginal estrogen (n = 7), or no treatment (n = 6) for 3 months. IDF imaging was performed monthly in all animals. Outcome Measurements and Statistical Analysis: The primary outcome was the proportion of image sequences containing capillary loops (angioarchitecture). Secondary outcomes included focal depth (epithelial thickness), and quantitative measures of vessel density and perfusion. Treatment effects were evaluated using ANCOVA and binary logistic regression.Results and LimitationsCompared to OVX‐only, ewes treated with estrogen demonstrated a higher capillary loops proportion (4% vs. 75%, p < 0.01), and higher focal depth (60 (IQR 60–80) vs. 80 (IQR 80–80) p < 0.05). CO$_{2}$ laser therapy did not change microcirculatory parameters. As the ewes' vaginal epithelium is thinner than that of humans, it may demand different laser settings. Conclusions: In a large animal model for GSM, CO$_{2}$ laser therapy does not affect microcirculatory outcomes related to GSM, whereas vaginal estrogen treatment does. Until more homogeneous and objective evidence about its efficacy is available, CO$_{2}$ laser therapy should not be adopted into widespread practice for treating GSM

Chorioallantoic and yolk sac placentation in the plains viscacha (Lagostomus maximus) - A caviomorph rodent with natural polyovulation

Objectives: Reproduction in the plains viscacha is characterized by the polyovulation of hundreds of oocytes, the loss of implantation and the development of 1-3 offspring. Our goal was to determine whether placental development was affected by these specializations. Study design: Thirteen placentas from early pregnancy to near-term pregnancy were analyzed using histological, immunohistochemical and transmission electron microscopy. Results: An inverted, villous yolk sac was present. Placentas were formed by the trophospongium, labyrinth and subplacenta. A lobulated structure with a hemomonochorial barrier was established early in pregnancy. Proliferating trophoblast that was clustered at the outer border and inside the labyrinth was responsible for placental growth. Trophoblast invasion resulted from the cellular trophoblast and syncytial streamers derived from the subplacenta. Different from other caviomorphs, numerous giant cells were observed. Conclusions: The principle processes of placentation in caviomorphs follow an extraordinarily stable pattern that is independent of specializations, such as polyovulation.Facultad de Ciencias Veterinaria

Intracranial V. cholerae Sialidase Protects against Excitotoxic Neurodegeneration

Converging evidence shows that GD3 ganglioside is a critical effector in a number of apoptotic pathways, and GM1 ganglioside has neuroprotective and noötropic properties. Targeted deletion of GD3 synthase (GD3S) eliminates GD3 and increases GM1 levels. Primary neurons from GD3S−/− mice are resistant to neurotoxicity induced by amyloid-β or hyperhomocysteinemia, and when GD3S is eliminated in the APP/PSEN1 double-transgenic model of Alzheimer's disease the plaque-associated oxidative stress and inflammatory response are absent. To date, no small-molecule inhibitor of GD3S exists. In the present study we used sialidase from Vibrio cholerae (VCS) to produce a brain ganglioside profile that approximates that of GD3S deletion. VCS hydrolyzes GD1a and complex b-series gangliosides to GM1, and the apoptogenic GD3 is degraded. VCS was infused by osmotic minipump into the dorsal third ventricle in mice over a 4-week period. Sensorimotor behaviors, anxiety, and cognition were unaffected in VCS-treated mice. To determine whether VCS was neuroprotective in vivo, we injected kainic acid on the 25th day of infusion to induce status epilepticus. Kainic acid induced a robust lesion of the CA3 hippocampal subfield in aCSF-treated controls. In contrast, all hippocampal regions in VCS-treated mice were largely intact. VCS did not protect against seizures. These results demonstrate that strategic degradation of complex gangliosides and GD3 can be used to achieve neuroprotection without adversely affecting behavior

Evidence for a Common Toolbox Based on Necrotrophy in a Fungal Lineage Spanning Necrotrophs, Biotrophs, Endophytes, Host Generalists and Specialists

The Sclerotiniaceae (Ascomycotina, Leotiomycetes) is a relatively recently evolved lineage of necrotrophic host generalists, and necrotrophic or biotrophic host specialists, some latent or symptomless. We hypothesized that they inherited a basic toolbox of genes for plant symbiosis from their common ancestor. Maintenance and evolutionary diversification of symbiosis could require selection on toolbox genes or on timing and magnitude of gene expression. The genes studied were chosen because their products have been previously investigated as pathogenicity factors in the Sclerotiniaceae. They encode proteins associated with cell wall degradation: acid protease 1 (acp1), aspartyl protease (asps), and polygalacturonases (pg1, pg3, pg5, pg6), and the oxalic acid (OA) pathway: a zinc finger transcription factor (pac1), and oxaloacetate acetylhydrolase (oah), catalyst in OA production, essential for full symptom production in Sclerotinia sclerotiorum. Site-specific likelihood analyses provided evidence for purifying selection in all 8 pathogenicity-related genes. Consistent with an evolutionary arms race model, positive selection was detected in 5 of 8 genes. Only generalists produced large, proliferating disease lesions on excised Arabidopsis thaliana leaves and oxalic acid by 72 hours in vitro. In planta expression of oah was 10–300 times greater among the necrotrophic host generalists than necrotrophic and biotrophic host specialists; pac1 was not differentially expressed. Ability to amplify 6/8 pathogenicity related genes and produce oxalic acid in all genera are consistent with the common toolbox hypothesis for this gene sample. That our data did not distinguish biotrophs from necrotrophs is consistent with 1) a common toolbox based on necrotrophy and 2) the most conservative interpretation of the 3-locus housekeeping gene phylogeny – a baseline of necrotrophy from which forms of biotrophy emerged at least twice. Early oah overexpression likely expands the host range of necrotrophic generalists in the Sclerotiniaceae, while specialists and biotrophs deploy oah, or other as-yet-unknown toolbox genes, differently