Emollients in dermatological creams: Early evaluation for tailoring formulation and therapeutic performance.

The targeted choice of the emollient of a cream determines its physicochemical properties and clinical effectiveness. This work researched the effects of emollient properties on the final characteristics and potential performance of oil-in-water dermatological creams. Seven emollients with different chemical characteristics and structures (alkane, triglyceride, ether, silicone, vegetable oils, and mineral oil) were tested in a model formulation. Early stability, pH, droplet size distribution, rheology, tackiness, adhesivity, spreadability, tribology, and release profile of a lipophilic substance model (in Franz cells, through a synthetic membrane, for six hours) were assessed. The creams had acid epicutaneous pH and a "shear-thinning" "solid-like" viscoelastic behavior. Among the seven emollients' properties, polarity, density, and viscosity were the most influential. Droplet parameters were the most impacted, pH and release were moderately affected, and the textural properties were lowly to moderately impacted. The emollient substitution in the model formulation affected the experimental parameters differently, allowing formulation optimization and tailoring its potential therapeutic performance regarding drug release, coadjutant effects, and dwell time on the skin. By looking at the creams' characteristics, it was possible to select the best-suited emollients for releasing a lipophilic drug, applying on painful skin, and formulation in wash-off products or leave-on protective barrier creams.

Volumetry after botulinum toxin A: the impact on abdominal wall compliance and endotracheal pressure.

PURPOSE: Botulinum toxin type A (BTA) is an adjuvant tool used in the preoperative optimization of complex hernias before abdominal wall reconstruction (AWR). This study aims to investigate changes in the abdominal cavity and hernia sac dimensions after BTA application. METHOD: A prospective study with 27 patients with a hernia defect of ≥ 10 cm and loss of domain (LOD) ≥ 20% underwent AWR. Computed tomography (CT) measurements and volumetry before and after the application of BTA were performed. Intraoperative and postoperative outcomes were evaluated. RESULTS: Imaging post-BTA revealed hernia width reduction of 1.9 cm (p = 0.002), lateral abdominal wall muscle elongation of 3.1 cm (p < 0.001), hernia volume reduction (HV) from 2.9 ± 0.9L to 2.4 ± 0.8L (p < 0.001), increase in abdominal cavity volume (ACV) from 9.7 ± 2.5L to 10.3L ± 2.4L (p = 0.003), and a reduction in the HV/ACV ratio from 30.2 ± 5% to 23.4 ± 6% (p < 0.001). Fascial closure was achieved in 92.6% of cases and component separation was required in 78%. The average variation in pulmonary plateau pressure was 3.53 cmH2O, and there were no postoperative respiratory failure recorded. At the 90-day follow-up, the wound morbidity rate was 25%, unplanned readmissions were 11%, and hernia recurrence 7.4%. CONCLUSION: BTA produces measurable volumetric changes in abdominal wall and appears to facilitate fascial closure. Further studies are required to determine the role of BTA in the surgical armamentarium for complex hernia repair.

Perceptions of change in the environment caused by the COVID-19 pandemic: Implications for environmental policy.

COVID-19 lockdown measures have impacted the environment with both positive and negative effects. However, how human populations have perceived such changes in the natural environment and how they may have changed their daily habits have not been yet thoroughly evaluated. The objectives of this work were to investigate (1) the social perception of the environmental changes produced by the COVID-19 pandemic lockdown and the derived change in habits in relation to i) waste management, energy saving, and sustainable consumption, ii) mobility, iii) social inequalities, iv) generation of noise, v) utilization of natural spaces, and, vi) human population perception towards the future, and (2) the associations of these potential new habits with various socio-demographic variables. First, a SWOT analysis identified strengths (S), weaknesses (W), opportunities (O), and threats (T) generated by the pandemic lockdown measures. Second, a survey based on the aspects of the SWOT was administered among 2370 adults from 37 countries during the period from February to September 2021. We found that the short-term positive impacts on the natural environment were generally well recognized. In contrast, longer-term negative effects arise, but they were often not reported by the survey participants, such as greater production of plastic waste derived from health safety measures, and the increase in e-commerce use, which can displace small storefront businesses. We were able to capture a mismatch between perceptions and the reported data related to visits to natural areas, and generation of waste. We found that age and country of residence were major contributors in shaping the survey participants ´answers, which highlights the importance of government management strategies to address current and future environmental problems. Enhanced positive perceptions of the environment and ecosystems, combined with the understanding that livelihood sustainability, needs to be prioritized and would reinforce environmental protection policies to create greener cities. Moreover, new sustainable jobs in combination with more sustainable human habits represent an opportunity to reinforce environmental policy.

Long-term commuting times and air quality relationship to COVID-19 in São Paulo.

The Coronavirus Disease 2019 (COVID-19) epidemic is an unprecedented global health crisis and the effects may be related to environmental and socio-economic factors. In São Paulo, Brazil, the first death occurred in March 2020 and since then the numbers have grown to 175 new deaths per day in April 2021, positioning the city as the epicenter of the number of cases and deaths in Brazil. São Paulo is one of the largest cities in the world with more than 12 million inhabitants, a fleet of about 8 million vehicles and frequent pollutant concentrations above recommended values. Social inequalities are evident in the municipality, similarly to other cities in the world. This paper focuses on transportation activities related to air pollution and associated with cardiovascular and respiratory diseases especially on people who developed comorbidities during their whole life. This study relates travel trip data to air quality analysis and expanded to COVID-19 disease. This work studied the relationship of deaths in São Paulo due to COVID-19 with demographic density, with family income, with the use of public transport and with atmospheric pollution for the period between March 17th, 2020 and April 29th, 2021. The main results showed that generally passenger kilometers traveled, commuting times and air quality related diseases increase with residential distance from the city center, and thus, with decreasing residential density. PM2.5 concentrations are positively correlated with COVID-19 deaths, regions with high urban densities have higher numbers of deaths and long-distance frequent trips can contribute to spread of the disease.

Global Forum of Cancer Surgeons: Cancer Surgery During the COVID-19 Pandemic: Impact and Lessons Learned.

BACKGROUND: The purpose of this article is to summarize the opinions of the surgical oncology leaders from the Global Forum of Cancer Surgeons (GFCS) about the global impact of COVID-19 pandemic on cancer surgery. METHODS: A panel session (virtual) was held at the annual Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care to address the impact of COVID-19 on cancer surgery globally. Following the virtual meeting, a questionnaire was sent to all the leaders to gather additional opinions. The input obtained from all the leaders was collated and analyzed to understand how cancer surgeons from across the world adapted in real-time to the impact of COVID-19 pandemic. RESULTS: The surgical oncology leaders noted that the COVID-19 pandemic led to severe disruptions in surgical cancer care across all domains of clinical care, education, and research. Several new changes/protocols associated with increased costs were implemented to deliver safe care. Leaders also noted that preexisting disparities in care were exacerbated, and the pandemic had a detrimental effect on well-being and financial status. CONCLUSIONS: The COVID-19 pandemic has led to severe disruptions in surgical cancer care globally. Leaders of the GFCS opined that new strategies need to be implemented to prepare for any future catastrophic events based on the lessons learned from the current events. The GFCS will embark on developing such a roadmap to ensure that surgical cancer care is preserved in the future regardless of any catastrophic global events.

Clinical outcomes and trans-syndesmotic screw frequency after posterior malleolar fracture osteosynthesis.

AIM: This study aimed to evaluate the clinical outcomes and the trans-syndesmotic screw frequency after trimalleolar ankle fractures with a posterior malleolus fracture involving <25% of the articular surface. MATERIAL AND METHODS: Retrospective comparative study. Patients with trimalleolar ankle fracture who underwent surgery between January 2011 and January 2018 were identified within the departments' fracture database. General demographics, treatment details, and fracture specific details (CT-scans) were assessed. Patients were grouped per the posterior malleolus fragment treatment: osteosynthesis (group 1) and non-osteosynthesis (group 2). RESULTS: 64 patients, 58.6 ± 17.8 years (range: 23-75), 68.8% female were eligible and follow up time was 43.1 ± 22.2 (range 24-96) months. The mean size of the posterior malleolus fragment was 14.7 ± 5.3% (range: 5-24). Posterior malleolus fragment treatment distribution: osteosynthesis (group 1) 31.2% and non- osteosynthesis (group 2) 68.8%. Group 1 showed significantly better clinical outcomes (p<0.05), AOOS (93.9 ± 5.79 (range: 73-99), AOFAS (91.5 ± 6.22 (range: 72-100) and VAS (0.8 ± 1.22 (range: 0-5) compared to Group 2, AOOS (84.25±8.34 (range: 63-100); AOFAS (84.75±8.05 (range: 58-100) and VAS (1.7 ± 1.38 (range: 0-6). Osteosynthesis of the posterior malleolus fragment significantly reduced the frequency of trans-syndesmotic screw (0%) compared to non-osteosynthesis posterior malleolus fragment (15.9%) (p < 0.05). The EQ-5D score was better in group 1 (1.08±0.27 (range: 1-2.2) compared to group 2 (1.27 ± 0.27 (range: 1-2.4) but with no statistical significance (p> 0.15). CONCLUSION: Posterior malleolus fragments (<25% of the articular surface) have significantly better clinical outcomes and significant decrease in trans-syndesmotic screw need following osteosynthesis.

Towards sustainable valorisation of Acacia melanoxylon biomass: Characterization of mature and juvenile plant tissues.

In Mediterranean area, Acacia melanoxylon biomass is an abundant waste material from non-native and invasive tree species control actions, requiring suitable disposal. Valorisation of such biomass residues requires its complete characterization to best approach the full potential of each plant material that could suit specific applications. This study compares mature and juvenile A. melanoxylon plant tissues (wood and bark) from two stands in different locations, regarding their chemical characteristics and organic growing media properties, such as mineral content and phytotoxicity effect for Lepidium sativum seeds. Juvenile bark (JB) showed greater total extractives (29%) extracted using solvents of increasing polarity (dichloromethane, ethanol, and water), followed by mature bark (MB) (21%). MB revealed the highest lignin content (>50%) suggesting material resistance to microbial biodegradation in horticultural applications. High barks phenolic content proved to be phytotoxic for cress seeds (null JB root index), although the toxic substances may be removed. After 1 week, ageing effect reduced MB phytototoxicity (root index > 60%) improving seed performance. Bark presented more mineral elements availability than wood. Wood high cellulose (>50%), low extractive (<9%) and moderate total lignin (<30%) contents can be attractive for pulp production, while bark growth medium profile may potentiate its application for horticultural uses. The future research on novel uses of A. melanoxylon plant residues can result in economic benefits that may alleviate management costs.

Chemical inhibition of ß-glucocerebrosidase does not affect phagocytosis and early containment of Leishmania by murine macrophages.

Gaucher disease is a lysosomal storage disease in which a genetic deficiency in ß-glucocerebrosidase leads to the accumulation of glycosphingolipids in lysosomes. Macrophages are amongst the cells most severely affected in Gaucher disease patients. One phenotype associated with Gaucher macrophages is the impaired capacity to fight bacterial infections. Here, we investigate whether inhibition of ß-glucocerebrosidase activity affects the capacity of macrophages to phagocytose and act on the early containment of human pathogens of the genus Leishmania. Towards our aim, we performed in vitro infection assays on macrophages derived from the bone marrow of C57BL/6 mice. To mimic Gaucher disease, macrophages were incubated with the ß-glucocerebrosidase inhibitor, conduritol B epoxide (CBE), prior to contact with Leishmania. This treatment guaranteed that ß-glucocerebrosidase was fully inhibited during the contact of macrophages with Leishmania, its enzymatic activity being progressively recovered along the 48 h that followed removal of the inhibitor. Infections were performed with L. amazonensis, L. infantum, or L. major, so as to explore potential species-specific responses in the context of ß-glucocerebrosidase inactivation. Parameters of infection, recorded immediately after phagocytosis, as well as 24 and 48 h later, revealed no noticeable differences in the infection parameters of CBE-treated macrophages relative to non-treated controls. We conclude that blocking ß-glucocerebrosidase activity during contact with Leishmania does not interfere with the phagocytic capacity of macrophages and the early onset of leishmanicidal responses.

Trapping and sorting of active matter in a periodic background potential.

We study, numerically, a system of active particles with either a single noise value or a mixture of equal proportions of particles with two noise values under the influence of an attractive periodic background potential, and we observe their diffusion regimes and trapping states. For the single noise system, we show that the slow diffusion is correlated to a significant particle trapping, while normal diffusion is seen for partial or no trapping. Our results indicate that low noise particles are less susceptible to the background, i.e., they have a smaller chance to be trapped as compared to higher noise particles for the same background, and that denser systems achieve a no-trapping state, unless for the largest noise value we studied. For the mixtures, we study the sorting of particles based on their noise value differences and observe that particles with distinct noises are trapped at distinct radii compared to a trap minimum, and, since these radii depend on the density, the latter should be well tuned in order to have an efficient sorting.

Quenched and annealed disorder mechanisms in comb models with fractional operators.

Recent experimental findings on anomalous diffusion have demanded novel models that combine annealed (temporal) and quenched (spatial or static) disorder mechanisms. The comb model is a simplified description of diffusion on percolation clusters, where the comblike structure mimics quenched disorder mechanisms and yields a subdiffusive regime. Here we extend the comb model to simultaneously account for quenched and annealed disorder mechanisms. To do so, we replace usual derivatives in the comb diffusion equation by different fractional time-derivative operators and the conventional comblike structure by a generalized fractal structure. Our hybrid comb models thus represent a diffusion where different comblike structures describe different quenched disorder mechanisms, and the fractional operators account for various annealed disorder mechanisms. We find exact solutions for the diffusion propagator and mean square displacement in terms of different memory kernels used for defining the fractional operators. Among other findings, we show that these models describe crossovers from subdiffusion to Brownian or confined diffusions, situations emerging in empirical results. These results reveal the critical role of interactions between geometrical restrictions and memory effects on modeling anomalous diffusion.

Future perspectives in addressing the global issue of vitamin D deficiency.

Vitamin D is a fundamentally critical nutrient that the human body requires to function properly. It plays an important role in musculoskeletal health due to its involvement in the regulation of calcium and phosphorus. Having a low level of vitamin D in the body may be detrimental for a wide range of health outcomes, including risk of osteoporotic and stress fractures, risk of CVD and some cancers, and lowering of the capability of the immune system. Vitamin D is an unusual nutrient; it is not a vitamin, in the true sense of the word but a pro-hormone. The main source of vitamin D is UV exposure, not dietary intake. Interestingly, there are two forms of vitamin D, vitamin D2 and vitamin D3, both of which are metabolised into 25-hydroxyvitamin D (25(OH)D) in the liver, the biomarker of vitamin D status. Vitamin D deficiency is a global public health problem, especially amongst older people and ethnic minority groups. The newest publication from the UK Government's Public Health England Department recommends that vitamin D intake should be 10 µg daily and this recommendation compares well (albeit lower) with other guidelines such as the Institute of Medicine recommendation of 15 µg for those aged 1-70 years and 20 µg for those 70 years or over. Few countries, however, have a specific vitamin D policy to prevent deficiency in populations. Finland leads the way, demonstrating impressive results in reducing population-level vitamin D deficiency through mandatory food fortification programmes. Collaboration between academia, government and industry, including countries from varying latitudes, is essential to identify long-term solutions to the global issue of vitamin D deficiency. This paper provides a narrative review of the evidence related to the role of vitamin D deficiency in health outcomes, outlines controversies regarding setting levels of adequacy, identifies the prevalence of vitamin D deficiency across the globe, and identifies population-level strategies adopted by countries to prevent vitamin D deficiency.

A High-Throughput BRET Cellular Target Engagement Assay Links Biochemical to Cellular Activity for Bruton's Tyrosine Kinase.

Protein kinases are intensely studied mediators of cellular signaling. While traditional biochemical screens are capable of identifying compounds that modulate kinase activity, these assays are limited in their capability of predicting compound behavior in a cellular environment. Here, we aim to bridge target engagement and compound-cellular phenotypic behavior by utilizing a bioluminescence resonance energy transfer (BRET) assay to characterize target occupancy within living cells for Bruton's tyrosine kinase (BTK). Using a diverse chemical set of BTK inhibitors, we determine intracellular engagement affinity profiles and successfully correlate these measurements with BTK cellular functional readouts. In addition, we leveraged the kinetic capability of this technology to gain insight into in-cell target residence time and the duration of target engagement, and to explore a structural hypothesis.

Extensions and solutions for nonlinear diffusion equations and random walks.

We investigate a connection between random walks and nonlinear diffusion equations within the framework proposed by Einstein to explain the Brownian motion. We show here how to properly modify that framework in order to handle different physical scenarios. We obtain solutions for nonlinear diffusion equations that emerge from the random walk approach and analyse possible connections with a generalized thermostatistics formalism. Finally, we conclude that fractal and fractional derivatives may emerge in the context of nonlinear diffusion equations, depending on the choice of distribution functions related to the spreading of systems.

Initialization of Single Spin Dressed States using Shortcuts to Adiabaticity.

We demonstrate the use of shortcuts to adiabaticity protocols for initialization, read-out, and coherent control of dressed states generated by closed-contour, coherent driving of a single spin. Such dressed states have recently been shown to exhibit efficient coherence protection, beyond what their two-level counterparts can offer. Our state transfer protocols yield a transfer fidelity of ∼99.4(2)% while accelerating the transfer speed by a factor of 2.6 compared to the adiabatic approach. We show bidirectionality of the accelerated state transfer, which we employ for direct dressed state population read-out after coherent manipulation in the dressed state manifold. Our results enable direct and efficient access to coherence-protected dressed states of individual spins and thereby offer attractive avenues for applications in quantum information processing or quantum sensing.

Assessment of the potential real pollen related allergenic load on the atmosphere of Porto city.

The knowledge of the allergen content in the atmosphere is a useful tool to stablish the risk allergy warnings for the sensitive people. In Portugal the main airborne allergenic pollen come from trees (such as Betula or Olea), grasses or weeds (mainly Urticaceae). The present study sought the quantification of the Bet v 1, Ole e 1, Lol p1 and Par j1-2 aeroallergen concentration as well as how weather variables influence in the pollen and allergen concentration in Porto city. Aerobiological study was carried out by a Hirst-type volumetric sampler for pollen collection and a Burkard Cyclone sampler for the aeroallergens. A regression analysis between pollen and allergens was conducted for the identification the allergenic risk days. High Pollen Allergen Potency in the atmosphere was observed considering the low levels of airborne pollen detected. A significant and positive correlation has been obtained between pollen and aeroallergen values with the temperatures whereas the correlation was negative with relative humidity, rainfall and wind speed. Back trajectory methodology was applied in order to analyse the discordances between pollen and allergen maximum concentrations. The analysis showed that when the pollen and allergen peaks were registered on the same day, air masses always comes from the continent. However, when the peaks do not coincide, the air mass comes from the continent in the case of the pollen peak and from the sea for the allergen peak. This behaviour can be a consequence of the high humidity in the air masses from the sea, which can benefit the allergen release from pollen grains. In our study it was observed that the available traditional information for allergenic Type I patients, corresponding to the amount of pollen grains in the bioaerosol, do not accurately identify the real allergenic load in the air.

Estimating physical properties from liquid crystal textures via machine learning and complexity-entropy methods.

Imaging techniques are essential tools for inquiring a number of properties from different materials. Liquid crystals are often investigated via optical and image processing methods. In spite of that, considerably less attention has been paid to the problem of extracting physical properties of liquid crystals directly from textures images of these materials. Here we present an approach that combines two physics-inspired image quantifiers (permutation entropy and statistical complexity) with machine learning techniques for extracting physical properties of nematic and cholesteric liquid crystals directly from their textures images. We demonstrate the usefulness and accuracy of our approach in a series of applications involving simulated and experimental textures, in which physical properties of these materials (namely: average order parameter, sample temperature, and cholesteric pitch length) are predicted with significant precision. Finally, we believe our approach can be useful in more complex liquid crystal experiments as well as for probing physical properties of other materials that are investigated via imaging techniques.

Range analysis of Eucalyptus globulus bark low-temperature hydrothermal treatment to produce a new component for growing media industry.

The use of industrial Eucalyptus globulus bark residues for organic growing media formulation was studied. Hydrothermal treatments were tested using Response Surface Methodology approach. Model design consisted of twelve combinations of temperature (T: 60-140 °C) and residential time (t: 20-60') to evaluate the effect on bark properties. Temperature had a significant effect in C mineralization and N immobilization rates, where the lowest responses (111.8 mmol CO2 kg-1 d-1 and NIR = 4.1 mmol N kg-1 d-1, respectively) compared to IEB (214.6 mmol CO2 kg-1 d-1 and 8.9 N kg-1 d-1, respectively) were suggested after modeling at 40 °C during 70'. Industrial bark was phytotoxic and treatments were effective for phytotoxicity removal. Industrial bark presented high air content but low water availability; treatments had no effect on bark physical properties and the use of demineralized water may have leached nutrient content. Results from pot experiment recommend the use of 25% (v v-1) of treated barks in future growing media formulations.

The GM2 ganglioside inhibits iNKT cell responses in a CD1d-dependent manner.

Invariant natural killer T (iNKT) cells are a subset of T lymphocytes that recognize lipid antigens presented on CD1d molecules at the surface of antigen-presenting cells. GM2 is a glycosphingolipid abundant in cellular membranes and known to bind CD1d molecules, but the functional consequences of this binding are not completely clarified. Herein, we analyzed the effect of GM2 in iNKT cell activation. We found that culturing antigen-presenting cells or total peripheral blood mononuclear cells with GM2 did not induce activation of human iNKT cells, implying that this lipid is not antigenic for human iNKT cells. To investigate if this lipid could inhibit iNKT cell activation, we simultaneously incubated antigen-presenting cells with GM2 and the iNKT cell antigen α-Galactosylceramide (α-GalCer) and used them to stimulate iNKT cells. We found that GM2 reduced human iNKT cell activation in a dose-dependent manner. An explanation for this effect could be a direct competition of GM2 with antigenic lipids for CD1d binding. This was demonstrated by the use of an antibody (L363) that stains mouse CD1d:α-GalCer complexes, as in the presence of GM2 the amount of CD1d:α-GalCer complexes are reduced. We further explored the consequences of chronic GM2 overload on human iNKT cells by analyzing iNKT cells in patients diagnosed with GM2 gangliosidoses. We found that pediatric patients present a higher frequency of circulating CD4+ iNKT cells and concomitant lower frequency of CD4-CD8- iNKTs. A lower percentage of iNKT cells expressing the NK marker CD161 was also observed in these patients. In contrast, in two adult patients studied, no differences on iNKT cell phenotype were observed. Altogether, this study uncovers a new role for GM2 in the modulation of iNKT cell activation, thus strengthening the central role of lipid metabolism in iNKT cell biology.