Tranexamic acid-loaded mesoporous silica microspheres as a hemostatic material

Bleeding management is considered essential for saving life both in the military and civilian field. There is still a need to develop topical hemostats that can stop bleeding and be used easily in the trauma sites. The aim of this work is to develop a hemostat based on mesoporous silica particles with large pores for bleeding control. Mesoporous silica microspheres (MSM) with particle size of 1.5 − 5 µm and pores diameter of 25 nm have been successfully synthesized and, for the first time, loaded with tranexamic acid (TXA) with a content of 4.7%w/w. The hemostatic activity of both the pure material and TXA-loaded material (TXA@MSM) was investigated. It was found that the blood clotting time was significantly shortened by both systems with respect to control. A hemolysis assay was performed to evaluate the hemolytic activity of MSM, and the result indicated that the material was blood compatible. A preliminary TXA in vitro release test was performed, showing the complete release of TXA from the carrier within one hour. Considering the above results, TXA@MSM can be considered a promising material for the development of new hemostats

Supercritical solvent impregnation of different drugs in mesoporous nanostructured zno

Supercritical solvent impregnation (SSI) is a green unconventional technique for preparing amorphous drug formulations. A mesoporous nanostructured ZnO (mesoNsZnO) carrier with 8-nm pores, spherical-nanoparticle morphology, and an SSA of 75 m2/g has been synthesized and, for the first time, subjected to SSI with poorly water-soluble drugs. Ibuprofen (IBU), clotrimazole (CTZ), and hydrocortisone (HC) were selected as highly, moderately, and poorly CO2-soluble drugs. Powder X-ray diffraction, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, nitrogen adsorption analysis, and ethanol extraction coupled with ultraviolet spectroscopy were employed to characterize the samples and quantify drug loading. Successful results were obtained with IBU and CTZ while HC loading was negligible, which could be related to different solubilities in CO2, drug size, and polarity. Successful SSI resulted in amorphous multilayer confinement of the drug. The mesoNsZnO-IBU system showed double drug loading than the mesoNsZnO-CTZ one, with a maximum uptake of 0.24 g/g. Variation of contact time during SSI of the mesoNsZnO-IBU system showed that drug loading triplicated between 3 and 8 h with an additional 30% increment between 8 h and 24 h. SSI did not affect the mesoNsZnO structure, and the presence of the adsorbed drug reduced the chemisorption of CO2 on the carrier surface

Savannah land cover characterisation: a quality assessment using Sentinel 1/2, Landsat, PALSAR and PlanetScope

The importance of savannahs worldwide has been widely acknowledged and documented. They are important ecosystems that are found on almost half of the African continent and a fifth of the Earth’s surface. They consist of varying densities of grasses and woody vegetation and,due to their complexity, they have been centre stage for a number of land system science debates, such as, equilibrium dynamics, land degradation and desertification, or their contribution to the global carbon cycle, to name but a few. Their significance is directly linked to the numerous recent efforts to map and monitor their land cover as accurately as possible, most commonly by employing Earth observation technologies. A recent case study by Symeonakis et al. (2018), carried out in a southern African savannah covering an area of ~44,000km2, tested the performance of different combinations of Landsat- and PALSAR-based metrics from the dry and wet seasons. They concluded that the combination of multi-sensor and multi-season data provides the best results when mapping the main land cover types of woody vegetation, grasses, crops and urban/bare. Here, we take this work further by testing the performance of 15 similar models, this time based on a combination of Sentinel-1 and Sentinel-2 metrics from the dry and wet season, using the same study area, training and validation samples (extracted from 0.5 m RGB aerial photography). Our results corroborate the findings of the previous study: the combination of the Sentinel optical and C-band radar data from both seasons yielded the most accurate land cover Random Forests classifications: overall accuracy of 87%, overall k: 0.83. Very high user’s and producer’s accuracies were also found, especially for the woody class (User’s: 93%; Producer’s: 93%), which is of primary concern in these savannah environments, due to its relevance to the land degradation processes that are dominant in the region: bush encroachment, overexploitation for fuelwood and deforestation. Similar to the Landsat/PALSAR study, the models based on SAR data only, were less accurate than the optical models. As anticipated, the L-band PALSAR data used in the previous study performed better in mapping the woody cover than their C-band counterparts, since L-band radiation is able to penetrate through the canopy layer and reach the woody stems and branches more efficiently. However, and interestingly, the Landsat-PALSAR study generally outperformed the Sentinel1/2 study, e.g. reporting the same omission but a 5% lower commission error for the woody class (estimated from the all-parameter model). Additionally, we tested a novel land cover configuration mapping accuracy approach using PlanetScope 3m-pixel data, with the view to assessing the quality of the mapping of landscape configuration (e.g. number of crop paddocks) and not only its composition (e.g. crop vs other cover). For five test areas of 170 km2 each, we performed object-based classifications of the PlanetScope imagery (two images per test area, one from the dry and one from the wet season). The results were less promising than those achieved for land cover composition: as an example, in one of our areas of focus, we determined 30 crop paddocks, 28 of which were of the circular centre pivot type ranging from 0.06 to 0.75 km2. For the same area, we mapped a significantly larger number of paddocks with the Sentinel 2 data, most of which were of the rectangular-shaped type. This discrepancy was attributed to the spectral similarity between the crop and grass land cover types, as well as the averaging effect of the lower spatial resolution of the Sentinel. Our findings, however, suggesting a multi-sensor and multi-seasonal approach, are an important addition to the emerging literature and can be used to guide efforts for achieving a highly accurate savannah land cover characterisation. Future work will investigate the use of the PlanetScope object-based classifications as training of the coarser-resolution models (e.g. Seninel 1- and 2-based metrics), not only for improving the mapping of land cover configuration, but also for mapping fractional cover, e.g. % woody vegetation

Resting pulmonary haemodynamics and shunting: a comparison of sea-level inhabitants to high altitude Sherpas

The incidence of blood flow through intracardiac shunt and intrapulmonary arteriovenous anastomoses (IPAVA) may differ between Sherpas permanently residing at high altitude (HA) and sea-level (SL) inhabitants as a result of evolutionary pressure to improve gas exchange and/or resting pulmonary haemodynamics. To test this hypothesis we compared sea-level inhabitants at SL (SL-SL; n = 17), during acute isocapnic hypoxia (SL-HX; n = 7) and following 3 weeks at 5050 m (SL-HA; n = 8 non-PFO subjects) to Sherpas at 5050 m (n = 14). inline image, heart rate, pulmonary artery systolic pressure (PASP) and cardiac index (Qi) were measured during 5 min of room air breathing at SL and HA, during 20 min of isocapnic hypoxia (SL-HX; inline image = 47 mmHg) and during 5 min of hyperoxia (inline image = 1.0; Sherpas only). Intracardiac shunt and IPAVA blood flow was evaluated by agitated saline contrast echocardiography. Although PASP was similar between groups at HA (Sherpas: 30.0 ± 6.0 mmHg; SL-HA: 32.7 ± 4.2 mmHg; P = 0.27), it was greater than SL-SL (19.4 ± 2.1 mmHg; P < 0.001). The proportion of subjects with intracardiac shunt was similar between groups (SL-SL: 41%; Sherpas: 50%). In the remaining subjects, IPAVA blood flow was found in 100% of subjects during acute isocapnic hypoxia at SL, but in only 4 of 7 Sherpas and 1 of 8 SL-HA subjects at rest. In conclusion, differences in resting pulmonary vascular regulation, intracardiac shunt and IPAVA blood flow do not appear to account for any adaptation to HA in Sherpas. Despite elevated pulmonary pressures and profound hypoxaemia, IPAVA blood flow in all subjects at HA was lower than expected compared to acute normobaric hypoxia

Cyclodextrin Complexes of Reduced Bromonoscapine in Guar Gum Microspheres Enhance Colonic Drug Delivery

Here, we report improved solubility and enhanced colonic delivery of reduced bromonoscapine (Red-Br-Nos), a cyclic ether brominated analogue of noscapine, upon encapsulation of its cyclodextrin (CD) complexes in bioresponsive guar gum microspheres (GGM). Phase−solubility analysis suggested that Red-Br-Nos complexed with β-CD and methyl-β-CD in a 1:1 stoichiometry, with a stability constant (Kc) of 2.29 × 103 M−1 and 4.27 × 103 M−1. Fourier transforms infrared spectroscopy indicated entrance of an O−CH2 or OCH3−C6H4−OCH3 moiety of Red-Br-Nos in the β-CD or methyl-β- CD cavity. Furthermore, the cage complex of Red-Br-Nos with β-CD and methyl-β-CD was validated by several spectral techniques. Rotating frame Overhauser enhancement spectroscopy revealed that the Ha proton of the OCH3−C6H4−OCH3 moiety was closer to the H5 proton of β-CD and the H3 proton of the methyl-β-CD cavity. The solubility of Red-Br-Nos in phosphate buffer saline (PBS, pH ∼ 7.4) was improved by ∼10.7-fold and ∼21.2-fold when mixed with β-CD and methyl-β-CD, respectively. This increase in solubility led to a favorable decline in the IC50 by ∼2-fold and ∼3-fold for Red-Br-Nos−β-CD-GGM and Red-Br-Nos−methyl-β-CD-GGM formulations respectively, compared to free Red-Br-Nos−β-CD and Red-Br-Nos−methyl-β-CD in human colon HT-29 cells. GGM-bearing drug complex formulations were found to be highly cytotoxic to the HT-29 cell line and further effective with simultaneous continuous release of Red-Br-Nos from microspheres. This is the first study to showing the preparation of drug-complex loaded GGMS for colon delivery of Red-Br-Nos that warrants preclinical assessment for the effective management of colon cancer

An integrated cell atlas of the lung in health and disease

Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1 + profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas. </p

An integrated cell atlas of the lung in health and disease

Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1+ profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas

Epigenetics and developmental programming of welfare and production traits in farm animals

The concept that postnatal health and development can be influenced by events that occur in utero originated from epidemiological studies in humans supported by numerous mechanistic (including epigenetic) studies in a variety of model species. Referred to as the ‘developmental origins of health and disease’ or ‘DOHaD’ hypothesis, the primary focus of large-animal studies until quite recently had been biomedical. Attention has since turned towards traits of commercial importance in farm animals. Herein we review the evidence that prenatal risk factors, including suboptimal parental nutrition, gestational stress, exposure to environmental chemicals and advanced breeding technologies, can determine traits such as postnatal growth, feed efficiency, milk yield, carcass composition, animal welfare and reproductive potential. We consider the role of epigenetic and cytoplasmic mechanisms of inheritance, and discuss implications for livestock production and future research endeavours. We conclude that although the concept is proven for several traits, issues relating to effect size, and hence commercial importance, remain. Studies have also invariably been conducted under controlled experimental conditions, frequently assessing single risk factors, thereby limiting their translational value for livestock production. We propose concerted international research efforts that consider multiple, concurrent stressors to better represent effects of contemporary animal production systems

Developmental adaptation to high altitude hypoxia

Experimental studies on animals and humans exposed to hypoxic stress have been reviewed. These data suggest that the influence of hypoxic stress, and the organism's response to it, are greater during growth than during adulthood. The organism's responses include alterations in the quantity and size of the alveolar units of the lungs, enlargement of the right ventricle of the heart, slower somatic growth as measured by birth weight and body size, increased aerobic capacity during maximal work, and greater control of ventilation. It is postulated that the organism is more sensitive to the influence of environmental factors during growth and development than during adulthood. Consequently, adaptive traits acquired during the developmental period have profound, long-term consequences, which are reflected in the physiological and morphological characteristics of the adult organism. It is concluded that the differences between the highland and lowland natives in their physiological performance and morphology are mostly due to adaptations acquired during the developmental period.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47840/1/484_2005_Article_BF01553707.pd