Dynamics of lymphatic regeneration and flow patterns after lymph node dissection.

Knowledge about the mechanisms of regeneration of the lymphatic vasculature after surgical trauma is essential for the development of strategies for the prevention and therapy of lymphedema. However, little is known about the alterations of lymphatic flow directly after surgical trauma. We investigated lymphatic function in mice using near-infrared imaging for a period of 4 weeks after surgeries that mimic sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND), by removal of the popliteal lymph node (LN) alone or together with the popliteal fat pad, respectively. SLNB-like surgery did not cause changes in lymphatic drainage in the majority of cases. In contrast, lymphatic drainage impairment shown by collecting vessel rupture, dermal backflow and rerouting of lymph flow via collateral vessels were observed after ALND-like surgery. All collateral vessels drained to the inguinal LN. These results indicate that less invasive surgery prevents lymphatic decompensation. They also reveal the development and maturation of collateral lymphatic vessels after extensive surgical trauma, which reroute the flow of lymph towards a different LN. These findings might be helpful for the development of strategies to prevent and/or treat post-surgical lymphedema

Coupled trace element and Sr-Nd-(Pb) isotopes in olivine-hosted melt inclusions from the Mariana arc

The Mariana arc forms part of the 2500 km Izu–Bonin–Mariana arc system caused by westward subduction of the Pacific Plate beneath the Philippine Sea Plate over the last ~45 Myr. The magmatism produced in this comparatively simple arc setting records a moderate flux of fluids and sediments from the downgoing plate, however, the low MgO (<6 wt.%) of the lavas imply that magma mixing, crystal fractionation and crustal assimilation mask the primitive melt compositions. Olivine-hosted melt inclusions (MIs), in contrast, provide access to melt trapped deep in the magmatic plumbing system allowing more precise determination of the nature and quantity of recycled components. Here we analyse coupled trace element and Sr-Nd(-Pb) isotope compositions of olivine-hosted MIs in five samples from four islands within the Central Island province: Agrigan (AGR2, AGR6), Pagan (PAG3), Guguan (GUG6) and Sarigan (SAG1). Bulk rock MgO contents range from 4 to 5.7 wt.% [1]. We specifically target melt inclusions in olivine phenocrysts with the highest fortsterite content (Fo = Mg/(Mg+Fe)*100): AGR: 80-86; PAG: 76-81; GUG: 76-88; SAG: 84-88 mol%. Trace element contents and ratios of the selected MIs record marked differences between islands and show larger variability compared to published bulk rock and MI compositions [2]. Ba/La and Th/Nb or La/Sm ratios – indicators of slab fluids versus sediment melts, respectively – confirm that Guguan inclusions are dominated by a fluid component whereas Agrigan and Sarigan reflect a larger sediment contribution. Pagan inclusions show intermediate compositions and a restricted range indicating the influence of both fluids and sediments. Sr-Nd-(Pb) isotope compositions of individual and pooled melt inclusions will be determined by wet chemistry and TIMS techniques using 10^13 Ω amplifier technology [3] to further identify and quantify the recycled components. [1] Elliott et al. (1997). Journal of Geophysical Research, 102: 14991-15019. [2] Kent & Elliott (2002). Chemical Geology, 183: 263-286. [3] Koornneef et al. (2019). Nature Communications 10, 323

Rainfall thresholds for the possible occurrence of landslides in Italy

Abstract. In Italy, rainfall is the primary trigger of landslides that frequently cause fatalities and large economic damage. Using a variety of information sources, we have compiled a catalogue listing 753 rainfall events that have resulted in landslides in Italy. For each event in the catalogue, the exact or approximate location of the landslide and the time or period of initiation of the slope failure is known, together with information on the rainfall duration D, and the rainfall mean intensity I, that have resulted in the slope failure. The catalogue represents the single largest collection of information on rainfall-induced landslides in Italy, and was exploited to determine the minimum rainfall conditions necessary for landslide occurrence in Italy, and in the Abruzzo Region, central Italy. For the purpose, new national rainfall thresholds for Italy and new regional rainfall thresholds for the Abruzzo Region were established, using two independent statistical methods, including a Bayesian inference method and a new Frequentist approach. The two methods proved complementary, with the Bayesian method more suited to analyze small data sets, and the Frequentist method performing better when applied to large data sets. The new regional thresholds for the Abruzzo Region are lower than the new national thresholds for Italy, and lower than the regional thresholds proposed in the literature for the Piedmont and Lombardy Regions in northern Italy, and for the Campania Region in southern Italy. This is important, because it shows that landslides in Italy can be triggered by less severe rainfall conditions than previously recognized. The Frequentist method experimented in this work allows for the definition of multiple minimum rainfall thresholds, each based on a different exceedance probability level. This makes the thresholds suited for the design of probabilistic schemes for the prediction of rainfall-induced landslides. A scheme based on four probabilistic thresholds is proposed. The four thresholds separate five fields, each characterized by different rainfall intensity-duration conditions, and corresponding different probability of possible landslide occurrence. The scheme can be implemented in landslide warning systems that operate on rainfall thresholds, and on precipitation measurements or forecasts

Can be gravitational waves markers for an extra-dimension?

The main issue of the present letter is to fix specific features (which turn out being independent of extradimension size) of gravitational waves generated before a dimensional compactification process. Valuable is the possibility to detect our prediction from gravitational wave experiment without high energy laboratory investigation. In particular we show how gravitational waves can bring information on the number of Universe dimensions. Within the framework of Kaluza-Klein hypotheses, a different morphology arises between waves generated before than the compactification process settled down and ordinary 4-dimensional waves. In the former case the scalar and tensor degrees of freedom can not be resolved. As a consequence if were detected gravitational waves having the feature here predicted (anomalous polarization amplitudes), then they would be reliable markers for the existence of an extra dimension.Comment: 5 pages, two figure, to appear on Int. Journ. Mod. Phys.

Decline of lymphatic vessel density and function in murine skin during aging.

Lymphatic vessels play important roles in the pathogenesis of many conditions that have an increased prevalence in the elderly population. However, the effects of the aging process on the lymphatic system are still relatively unknown. We have applied non-invasive imaging and whole-mount staining techniques to assess the lymphatic vessel function and morphology in three different age groups of mice: 2 months (young), 7 months (middle-aged), and 18 months (aged). We first developed and validated a new method to quantify lymphatic clearance from mouse ear skin, using a lymphatic-specific near-infrared tracer. Using this method, we found that there is a prominent decrease in lymphatic vessel function during aging since the lymphatic clearance was significantly delayed in aged mice. This loss of function correlated with a decreased lymphatic vessel density and a reduced lymphatic network complexity in the skin of aged mice as compared to younger controls. The blood vascular leakage in the skin was slightly increased in the aged mice, indicating that the decreased lymphatic function was not caused by a reduced capillary filtration in aged skin. The decreased function of lymphatic vessels with aging might have implications for the pathogenesis of a number of aging-related diseases

Beyond Trial and Error: A Systematic Development of Liposomes Targeting Primary Macrophages

Monocytes/macrophages are phagocytic innate immune cells playing a pivotal role in tissue homeostasis, inflammation, and antitumor immunity in a microenvironment-dependent manner. By expressing pattern recognition and scavenger receptors on their surface, macrophages selectively take up pathogens, cellular debris, and often—undesirably—drug delivery systems. On the other hand, the propensity of phagocytic cells to internalize particulate drug carriers is used to load them with a cargo of choice, turning the monocytes/macrophages into a diagnostic or therapeutic Trojan horse. Identifying the ideal physicochemical properties of particulate carriers such as liposomes to achieve the most efficient macrophage-mediated drug delivery has been object of extensive research in the past, but the studies reported so far rely solely on trial-and-error approaches. Herein, a design of experiment (DoE) strategy to identify the optimal liposomal formulation is proposed, fully characterized in terms of size, surface charge, and membrane fluidity, to maximize macrophage targeting. The findings are validated using mouse bone marrow-derived macrophages, a primary preparation modeling in vivo monocyte-derived macrophages, thus confirming the robustness and versatility of the systematic and iterative approach and suggesting the promising potential of the DoE approach for the design of cell-targeting delivery systems

Pollen extract in association with vitamins provides early pain relief in patients affected by chronic prostatitis/chronic pelvic pain syndrome

The therapeutic efficacy for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is currently unsatisfactory. The aim of the present study was to assess the safety and efficacy of pollen extract in association with vitamins (DEPROX 500®) in males with CP/CPPS. All patients with a diagnosis of CP/CPPS attending the same urologic centre between March and October 2012 were enrolled in this randomised controlled phase III study. Participants were randomised to receive oral capsules of DEPROX 500® (two capsules every 24 h) or ibuprofen (600 mg, one tablet three times a day) for four weeks. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score and Quality of Well-Being (QoL) questionnaires were used. In the intention-to-treat analysis, 87 males (25 class IIIa and 62 class IIIb) with a mean age of 33.6±5.9 years were randomly allocated to the DEPROX 500® (n=41) or ibuprofen (n=46) treatment groups. At the follow-up examination (following one month of treatment), in the DEPROX 500® group, 31/41 patients (75.6%) reported an improvement in quality of life, defined as a reduction of the NIH-CPSI total score by ≥25%, compared with 19/46 (41.3%) in the control group (P=0.002). The greater improvement in the DEPROX 500® group compared with the ibuprofen group was statistically significant (treatment difference in the NIH-CPSI pain domain, -2.14±0.51, P&lt;0.001; QoL scores, P=0.002). All patients were negative at the Meares-Stamey test evaluation. Adverse events were less frequent in the DEPROX 500® group than in the ibuprofen group. The DEPROX 500® treatment significantly improved total symptoms, pain and quality of life compared with ibuprofen in patients with CP/CPPS, without severe side-effects

Efficacy of pulsatile flow perfusion in adult cardiac surgery: Hemodynamic energy and vascular reactivity

Background: The role of pulsatile (PP) versus non-pulsatile (NP) flow during a cardiopulmonary bypass (CPB) is still debated. This study’s aim was to analyze hemodynamic effects, endothelial reactivity and erythrocytes response during a CPB with PP or NP. Methods: Fifty-two patients undergoing an aortic valve replacement were prospectively randomized for surgery with either PP or NP flow. Pulsatility was evaluated in terms of energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE). Systemic (SVRi) and pulmonary (PVRi) vascular resistances, endothelial markers levels and erythrocyte nitric-oxide synthase (eNOS) activity were collected at different perioperative time-points. Results: In the PP group, the resultant EEP was 7.3% higher than the mean arterial pressure (MAP), which corresponded to 5150 ± 2291 ergs/cm3 of SHE. In the NP group, the EEP and MAP were equal; no SHE was produced. The PP group showed lower SVRi during clamp-time (p = 0.06) and lower PVRi after protamine administration and during first postoperative hours (p = 0.02). Lower SVRi required a higher dosage of norepinephrine in the PP group (p = 0.02). Erythrocyte eNOS activity results were higher in the PP patients (p = 0.04). Renal function was better preserved in the PP group (p = 0.001), whereas other perioperative variables were comparable between the groups. Conclusions: A PP flow during a CPB results in significantly lower SVRi, PVRi and increased eNOS production. The clinical impact of increased perioperative vasopressor requirements in the PP group deserves further evaluation