Background Aortic wall strains are indicators of biomechanical changes of the aorta due to aging or progressing pathologies such as aortic aneurysm. We investigated the potential of time-resolved ...three-dimensional ultrasonography coupled with speckle-tracking algorithms and finite element analysis as a novel method for noninvasive in vivo assessment of aortic wall strain. Methods Three-dimensional volume datasets of 6 subjects without cardiovascular risk factors and 2 abdominal aortic aneurysms were acquired with a commercial real time three-dimensional echocardiography system. Longitudinal and circumferential strains were computed offline with high spatial resolution using a customized commercial speckle-tracking software and finite element analysis. Indices for spatial heterogeneity and systolic dyssynchrony were determined for healthy abdominal aortas and abdominal aneurysms. Results All examined aortic wall segments exhibited considerable heterogenous in-plane strain distributions. Higher spatial resolution of strain imaging resulted in the detection of significantly higher local peak strains ( p ≤ 0.01). In comparison with healthy abdominal aortas, aneurysms showed reduced mean strains and increased spatial heterogeneity and more pronounced temporal dyssynchrony as well as delayed systole. Conclusions Three-dimensional ultrasound speckle tracking enables the analysis of spatially highly resolved strain fields of the aortic wall and offers the potential to detect local aortic wall motion deformations and abnormalities. These data allow the definition of new indices by which the different biomechanical properties of healthy aortas and aortic aneurysms can be characterized.
Background Newborns display distinct immune responses, leaving them vulnerable to infections and impairing immunization. Targeting newborn dendritic cells (DCs), which integrate vaccine signals into ...adaptive immune responses, might enable development of age-specific vaccine formulations to overcome suboptimal immunization. Objective Small-molecule imidazoquinoline Toll-like receptor (TLR) 8 agonists robustly activate newborn DCs but can result in reactogenicity when delivered in soluble form. We used rational engineering and age- and species-specific modeling to construct and characterize polymer nanocarriers encapsulating a TLR8 agonist, allowing direct intracellular release after selective uptake by DCs. Methods Chemically similar but morphologically distinct nanocarriers comprised of amphiphilic block copolymers were engineered for targeted uptake by murine DCs in vivo , and a range of TLR8 agonist–encapsulating polymersome formulations were then synthesized. Novel 96-well in vitro assays using neonatal human monocyte-derived DCs and humanized TLR8 mouse bone marrow–derived DCs enabled benchmarking of the TLR8 agonist–encapsulating polymersome formulations against conventional adjuvants and licensed vaccines, including live attenuated BCG vaccine. Immunogenicity of the TLR8 agonist adjuvanted antigen 85B (Ag85B)/peptide 25–loaded BCG-mimicking nanoparticle formulation was evaluated in vivo by using humanized TLR8 neonatal mice. Results Although alum-adjuvanted vaccines induced modest costimulatory molecule expression, limited TH -polarizing cytokine production, and significant cell death, BCG induced a robust adult-like maturation profile of neonatal DCs. Remarkably, TLR8 agonist polymersomes induced not only newborn DC maturation profiles similar to those induced by BCG but also stronger IL-12p70 production. On subcutaneous injection to neonatal mice, the TLR8 agonist–adjuvanted Ag85B peptide 25 formulation was comparable with BCG in inducing Ag85B-specific CD4+ T-cell numbers. Conclusion TLR8 agonist–encapsulating polymersomes hold substantial potential for early-life immunization against intracellular pathogens. Overall, our study represents a novel approach for rational design of early-life vaccines.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Objective
The diagnosis of oral lesions is often challenging for primary healthcare providers, which explains the high number of referrals to specialist care. This favors increases in waiting lines ...and delays in diagnosis, contributing to high mortality rates from oral cancer. This study aimed to summarize the experience of the EstomatoNet, a telediagnosis program catering to primary care dentists and physicians from southern Brazil.
Study design
This exploratory study included all queries received by EstomatoNet from June 2015 to December 2016. Health providers (71 dentists and 18 physicians from primary care) submitted requests including clinical information and photographs of oral lesions by means of a cloud‐based platform. Specialized oral medicine teleconsultants received the data, conveyed a diagnostic hypothesis, and conveyed management recommendations.
Results
Actinic cheilitis (n = 41, 15.8%), squamous cell carcinoma (n = 22, 8.5%), and inflammatory hyperplasia (21, 8.1%) were the most frequent diagnoses. Teleconsultants recommended referral to specialists in 42.9% of the cases, total biopsy in 23.6%, and follow‐up in 16.2%. After the EstomatoNet use, the intention to refer the patients to face‐to‐face consultation reduced from 96.9% to 35.1%.
Conclusion
Telediagnosis for oral lesions is feasible and has potential to improve the quality of primary health care by bridging the gap between primary and specialized health care.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To evaluate and compare irinotecan elution kinetics of two drug-eluting embolic agents in a porcine model.
Embolization of the left liver lobe was performed in 16 domestic pigs, with groups of two ...receiving 1 mL of DC Bead M1 (70-150 µm) or Embozene TANDEM (75 µm) loaded with 50 mg irinotecan. Irinotecan plasma levels were measured at 0, 10, 20, 30, 60, 120, 180, and 240 minutes after completed embolization and at the time of euthanasia (24 h, 48 h, 72 h, or 7 d). Liver tissue samples were taken to measure irinotecan tissue concentrations.
The highest irinotecan plasma concentrations of both embolic agents were measured 10 and 20 minutes after embolization, and concentrations were significantly higher for DC Bead M1 versus Embozene TANDEM (P = .0019 and P = .0379, respectively). At 48 hours and later follow-up, no irinotecan was measurable in the plasma. For both embolic agents, the highest irinotecan tissue concentration was found after 24 hours and decreased in a time-dependent manner at later follow-up intervals. Additionally, SN-38 tissue levels for both agents were therapeutic at 24 hours, with therapeutic levels of SN-38 at 48 hours in one liver embolized with TANDEM particles. Histopathologic analysis revealed ischemic, inflammatory, and fibrotic tissue reactions.
Irinotecan is measurable in plasma and hepatic tissue after liver embolization with both types of irinotecan-eluting embolic agents. DC Bead M1 shows early burst elution kinetics, whereas Embozene TANDEM has a lower and slower release profile. The initial burst is significantly greater after embolization with DC Bead M1 than with Embozene TANDEM.
Immediately after sampling, leukocyte counts in native cerebrospinal fluid (CSF) start to decrease rapidly. As the time lapse between CSF collection to analysis is not routinely registered, the ...clinical significance of decreasing cell counts in native CSF is not known. Earlier data suggest that addition of serum-containing medium to CSF directly after sampling prevents this rapid decrease in leukocyte counts and, thus, may improve the accuracy of CSF cell counting and cell characterization. Here, we prospectively examined the effect of storage time after lumbar puncture on counts of leukocytes and their major subsets in both native CSF and after immediate addition of serum-containing medium, measured by flow cytometry and microscopy. We collected CSF samples of 69 patients in tubes with and tubes without serum-containing medium and determined counts of leukocytes and subsets at 30 minutes, 1 hour, and 5 hours after sampling. Compared to cell counts at 30 minutes, no significant decrease in cell number was observed in CSF with serum-containing medium 1 and 5 hours after sampling, except for the granulocytes at 1 hour. In native CSF, approximately 50% of leukocytes and all their subsets were lost after 1 hour, both in flow cytometric and microscopic counting. In 6/7 (86%) samples with mild pleocytosis (5–15 × 10
6
leukocytes/l), native CSF at 1 hour was incorrectly diagnosed as normocellular. In conclusion, addition of serum-containing medium to CSF directly after sampling prevents cell loss and allows longer preservation of CSF cells prior to analysis, both for microscopic and flow cytometric enumeration. We suggest that this protocol results in more accurate CSF cell counts and may prevent incorrect conclusions based on underestimated CSF cell counts.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To analyze irreversible electroporation (IRE) of the pig kidney with involvement of the renal pelvis.
IRE of renal tissue including the pelvis was performed in 10 kidneys in five pigs. Three study ...groups were defined: group I (two applicators with parallel configuration; n = 11), group II (three applicators with triangular configuration; n = 2), and group III (six applicators with complex configuration; n = 3). After IRE and before euthanasia, pigs underwent contrast-enhanced computed tomography (CT). Technical aspects (radial distance of applicators, resulting mean current), clinical outcome (complications, blood samples), and three-dimensional CT rendering for assessment of the treatment zone (short axis, circularity) were assessed.
Radial distances of applicators were 14.3 mm ± 2.8 in group I, 12.3 mm ± 1.9 in group II, and 16.4 mm ± 3.5 in group III. Resulting mean currents were 25.7 A ± 6.5 in group I, 27.0 A ± 7.1 in group II, and 39.4 A ± 8.9 in group III. In group III, two perirenal hematomas were identified. There was no damage to the renal pelvis. During IRE, clinical blood parameters and cardiovascular markers did not change significantly. Short axis measurements were 20.6 mm ± 3.6 in group I, 31.9 mm ± 8.2 in group II, and 39.3 mm ± 2.4 in group III (P < .01 between groups). Circularity scores were 0.8 ± 0.2 in group I, 0.7 ± 0.1 in group II, and 0.7 ± 0.1 in group III, with a score of 1 indicating perfect roundness (P value not significant).
IRE of the pig kidney with involvement of the renal pelvis is feasible and safe. Size but not shape of the treatment zone is significantly affected by applicator configuration.
The Siberian Traps volcanism is widely considered the main cause of the end-Permian mass extinction, the greatest biological crisis in the Earth history. While the extinction is interpreted as ...catastrophic and sudden with estimates of duration of approximately 35–40 thousand years from marine strata in South China, various lines of evidence have emerged for a more complex, prolonged, and diachronous extinction pattern. We present here the results of a multidisciplinary study of the Permian-Triassic continental transition in the Kuznetsk Basin, Russia. The region is proximal to the Siberian Traps LIP and the detrimental effects of the flood basalt volcanism in the Kuznetsk Basin may have been of similar scale as in the main area of the Siberian Traps distribution (Tunguska and Taymyr regions). Whereas earlier work has placed the Permian-Triassic boundary position between the coal-bearing Tailugan Formation and the volcanoclastic Maltsev Formation, here we revised the traditional model using three independent methods: radioisotopic CA-IDTIMS U-Pb zircon ages, δ13Corg isotope values and paleomagnetic proxies. The regional extinction of the humid-dominated forest flora (cordaites) and the aridity-induced biotic turnover in the Kuznetsk Basin occurred 820 kyr earlier than the end-Permian extinction event recorded in South China at 251.94 Ma. The biota in Kuznetsk Basin at the turnover subsequently diversified (with some exceptions) across the Permian-Triassic transition.
By compiling a large taxonomic database, we find that marine and terrestrial biotic diversity in Siberia progressively increased from the beginning of the Permian up to the middle Roadian (early Guadalupian global glacial event). After that time, the diversity at the species and generic level progressively and slowly declined towards the aforementioned latest Changhsingian (252.76 Ma) biotic turnover. Starting from this time, the biota rapidly diversified in the latest Changhsingian and Early-Middle Triassic. We suggest that the Permian-Triassic mass extinction mostly occurred in the tropics and subtropics due to the strong climatic warming, which was relatively low in late Changhsingian and gradually but quickly extends in the latest Changhsingian to an abnormally high temperature and extremely low oxygenated water in the oceans that was deadly for most marine animals. The warm climate shift poleward during Permian-Triassic transition in the middle-high latitudes caused the replacement (turnover) of the humid-related biotas by the dry climate-related and more diverse communities, which continued to expand throughout the Triassic in both marine and terrestrial habitats. The pattern of the Permian-Triassic event in both marine and terrestrial habitats was more intricate in terms of extinction, turnover, and diversity of biota within the different climatic zones and environmental habitats than has been generally considered.
•Permian-Triassic transition in Kuznetsk Basin (Russia) constrained with CA-IDTIMS dates.•Regional biota evolutionary turnover in the region occurs 820 kyr earlier than in South China.•The biota in Kuznetsk Basin diversified across the Permian-Triassic transition.•Permian-Triassic extinction mostly occurs in the tropics due to the strong climatic warming.•Siberian basalts as a cause of the extinction at the P-T boundary remain questionable.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Purpose To evaluate the utility of Endothelial/Descemet’s membrane complex (En/DM) characteristics in diagnosing corneal graft rejection. Design Diagnostic reliability study. Methods 139 ...eyes (96 corneal grafts post penetrating keratoplasty or Descemet’s stripping automated endothelial keratoplasty: 40 clear, 23 actively rejecting, 24 rejected and 9 non-immunological failed grafts, along with 43 age-matched control eyes) were imaged using high-definition optical coherence tomography. Images were used to describe En/DM and measure central corneal thickness (CCT) and central En/DM thickness (DMT). En/DM rejection index (DRI) was computed to detect the relative En/DM thickening to the entire cornea. Results In actively rejecting grafts, DMT and DRI were significantly greater than controls and clear grafts (28, 17 and 17 μm and 1.5, 1 and 1, respectively; P<0.001). Rejected grafts had the highest DMT and DRI compared to all groups (59 μm and 2.1; P<0.001). DMT and DRI showed excellent accuracy, significantly better than that of CCT, in differentiating actively rejecting from clear grafts (100% and 96% sensitivity; 92.5% and 92.5% specificity), actively rejecting from rejected grafts (88% and 83% sensitivity; 91% and 83% specificity) and non-immunological failed from rejected grafts (100% and 100% sensitivity; 88% and 100% specificity). DMT correlated significantly with rejection severity (P<0.001). Conclusions In corneal grafts, in vivo relative thickening of the En/DM is diagnostic of graft rejection as measured by DMT and DRI. These indices have excellent accuracy, sensitivity and specificity in detecting graft immunological status, superior to CCT. DMT is a quantitative index that correlates accurately with the severity of rejection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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