The Aptian was characterized by dramatic tectonic, oceanographic, climatic and biotic changes and its record is punctuated by Oceanic Anoxic Events (OAEs). The timing and duration of these events are ...still contentious, particularly the age of the Barremian-Aptian boundary. This study presents a cyclostratigraphic evaluation of a high-resolution multiproxy dataset (δ
C, δ
O, MS and ARM) from the Poggio le Guaine core. The identification of Milankovitch-band imprints allowed us to construct a 405-kyr astronomically-tuned age model that provides new constraints for the Aptian climato-chronostratigraphic framework. Based on the astronomical tuning, we propose: (i) a timespan of ~7.2 Myr for the Aptian; (ii) a timespan of ~420 kyr for the magnetic polarity Chron M0r and an age of ~120.2 Ma for the Barremian-Aptian boundary; and (iii) new age constraints on the onset and duration of Aptian OAEs and the 'cold snap'. The new framework significantly impacts the Early Cretaceous geological timescale.
Detailed information about lung cancer patients requiring admission to intensive care units (ICUs) is mostly restricted to single-center studies. Our aim was to evaluate the clinical characteristics ...and outcomes of lung cancer patients admitted to ICUs.
Prospective multicenter study in 449 patients with lung cancer (small cell, n = 55; non-small cell, n = 394) admitted to 22 ICUs in six countries in Europe and South America during 2011. Multivariate Cox proportional hazards frailty models were built to identify characteristics associated with 30-day and 6-month mortality.
Most of the patients (71%) had newly diagnosed cancer. Cancer-related complications occurred in 56% of patients; the most common was tumoral airway involvement (26%). Ventilatory support was required in 53% of patients. Overall hospital, 30-day, and 6-month mortality rates were 39%, 41%, and 55%, respectively. After adjustment for type of admission and early treatment-limitation decisions, determinants of mortality were organ dysfunction severity, poor performance status (PS), recurrent/progressive cancer, and cancer-related complications. Mortality rates were far lower in the patient subset with nonrecurrent/progressive cancer and a good PS, even those with sepsis, multiple organ dysfunctions, and need for ventilatory support. Mortality was also lower in high-volume centers. Poor PS predicted failure to receive the initially planned cancer treatment after hospital discharge.
ICU admission was associated with meaningful survival in lung cancer patients with good PS and non-recurrent/progressive disease. Conversely, mortality rates were very high in patients not fit for anticancer treatment and poor PS. In this subgroup, palliative care may be the best option.
Cellulose-based materials have been extensively investigated due to their abundance, renewable nature, and low abrasiveness and density. Cellulose nanocrystals (CNCs) stand out as nanometric ...particles of increasing technological interest, and also due to their potential use as nano-reinforcements to polymer composites. Since the effect of ultrasonic treatment on the structure and properties of CNCs is not yet fully understood, in this study the effect of ultrasonic output and hydrolysis time on yield and morphological, structural, and thermal properties of nanocrystals from microcrystalline cellulose (MCC) was studied. CNCs were prepared by conventional hydrolysis and compared to sonochemical extraction using 64 vol% H
2
SO
4
at 45 °C. Sonication power varied from 50, 70 and 90%, and for each value a kinetic study was performed as a function of hydrolysis time until a colloidal gel suspension was obtained. Results showed that it was possible to obtain CNCs from MCC with reduced extraction time, whose thermal stability, aspect ratio and crystallinity index are comparable to those obtained by conventional acid hydrolysis. The ultrasound power intensity was the most important parameter to increase CNC sonochemical extraction productivity. The optimal CNC yield occurred at predetermined hydrolysis time intervals for each set of variables of low-intensity ultrasound-assisted hydrolysis. The disaggregation of freshly produced CNCs from MCC particles occurred simultaneously to size reduction of previously produced CNCs and conversion of amorphous phase into sugars. Due to the non-selective nature of sonochemical hydrolysis, it was proposed that hydrolysis proceeds regardless of the size and crystallinity degree of cellulose particles dispersed in the acidic medium. Therefore, there was an optimal hydrolysis time as a function of CNC yield for each set of hydrolysis parameters, since prolonged extraction times leaded to deterioration of the morphological and structural properties of CNCs.
We study the spreading of SARS-CoV-2 in Brazil based on official data available since March 22, 2020. Calculations are done via an adaptive susceptible–infected–removed (SIR) model featuring ...dynamical recuperation and propagation rates. We are able reproduce the number of confirmed cases over time with less than 5% error and also provide with short- and long-term predictions. The model can also be used to account for the epidemic dynamics in other countries with great accuracy.
•SARS-CoV-2 in Brazil based on official data available since March 22, 2020.•Adaptive susceptible–infected–removed (SIR) model can reproduce the number of confirmed cases over time.•It is possible to predict the epidemic progression in the near future.
Delirium and coma are a frequent source of morbidity for ICU patients. Several factors are associated with the prognosis of mechanically ventilated (MV) cancer patients, but no studies evaluated ...delirium and coma (acute brain dysfunction). The present study evaluated the frequency and impact of acute brain dysfunction on mortality.
The study was performed at National Cancer Institute, Rio de Janeiro, Brazil. We prospectively enrolled patients ventilated >48 h with a diagnosis of cancer. Acute brain dysfunction was assessed during the first 14 days of ICU using RASS/CAM-ICU. Patients were followed until hospital discharge. Univariate and multivariable analysis were performed to evaluate factors associated with hospital mortality.
170 patients were included. 73% had solid tumors, age 65 53-72 (median, IQR 25%-75%) years. SAPS II score was 5446-63 points and SOFA score was (7 6-9) points. Median duration of MV was 13 (6-21) days and ICU stay was 14 (7.5-22) days. ICU mortality was 54% and hospital mortality was 66%. Acute brain dysfunction was diagnosed in 161 patients (95%). Survivors had more delirium/coma-free days 4(1,5-6) vs 1(0-2), p<0.001. In multivariable analysis the number of days of delirium/coma-free days were associated with better outcomes as they were independent predictors of lower hospital mortality 0.771 (0.681 to 0.873), p<0.001.
Acute brain dysfunction in MV cancer patients is frequent and independently associated with increased hospital mortality. Future studies should investigate means of preventing or mitigating acute brain dysfunction as they may have a significant impact on clinical outcomes.
Aim
To evaluate the efficacy of selective and nonselective inhibitors of cyclooxygenase‐2 enzymes in the treatment of experimental apical periodontitis induced by bacterial lipopolysaccharide (LPS) ...in vivo in a mouse model.
Methodology
Thirty‐six C57BL/6 mice were used. After access cavity preparation, a solution containing E. coli LPS (1.0 µg µL−1) was inoculated into the root canals of the mandibular and maxillary right first molars (n = 72) After 30 days, apical periodontitis was established and the animals were systemically treated with celecoxib, a selective COX‐2 inhibitor (15 mg kg−1), or indomethacin, a nonselective COX‐2 inhibitor (5 mg kg−1), for 7 and 14 days. Blocks containing teeth and bone were removed for histopathological and histometric analyses (haematoxylin and eosin), evaluation of osteoclasts numbers (tartrate‐resistant acid phosphatase enzyme – TRAP) and immunohistochemistry for RANK, RANKL and OPG. Gene expression was performed using reverse transcription and real‐time polymerase chain reaction (qRT‐PCR) for RANK, RANKL, OPG, TRAP, MMP‐9, cathepsin K and calcitonin receptor. Histopathological, histometric, TRAP, immunohistochemistry and qRT‐PCR data were evaluated using Kruskal–Wallis followed by Dunn’s test (α = 0.05).
Results
Systemic administration of celecoxib for 7 and 14 days prevented periapical bone resorption (P < 0.0001), differently from indomethacin that exacerbated bone resorption at 7 days (P < 0.0001) or exerted no effect at 14 days (P = 0.8488). Celecoxib treatment reduced osteoclast formation in apical periodontitis, regardless of the period of treatment (P < 0.0001 for 7 days and P = 0.026 for 14 days). Administration of celecoxib or indomethacin differentially modulated the expression of genes involved in bone resorption. At 7 days, celecoxib and indomethacin treatment significantly inhibited expression of mRNA for cathepsin K (P = 0.0005 and P = 0.016, respectively) without changing TRAP, MMP‐9 and calcitonin receptor gene expression. At 14 days, celecoxib significantly inhibited expression of mRNA for MMP‐9 (P < 0.0001) and calcitonin receptor (P = 0.004), whilst indomethacin exerted no effect on MMP‐9 (P = 0.216) and calcitonin receptor (P = 0.971) but significantly augmented cathepsin K gene expression (P = 0.001).
Conclusions
The selective COX‐2 inhibitor celecoxib reduced osteoclastogenic signalling and activity that dampened bone resorption in LPS‐induced apical periodontitis in mice, with greater efficacy than the nonselective inhibitor indomethacin.
Background: Patient preferences should be considered when prescribing topical treatments to drive up adherence and improve clinical outcomes.
Objective: The aim of this work was to identify the most ...important attributes of topical medicines for psoriasis treatment in the patients' view, and explore the sociodemographic and clinical determinants of these preferences.
Methods: A questionnaire for the evaluation of the relevancy given to specific attributes of topical medicines used for psoriasis treatment was developed (PSO-TOPAP) and was applied to a total of seventy-nine patients, members of the Portuguese Association of Psoriasis (PSOPortugal) or outpatients of a dermatology unit of a central hospital.
Results: Overall, attributes belonging to the formulation and application domains were greatly valued over attributes related to the container. Only a small number of patient preferences was influenced by age, gender, duration of the disease and age at first diagnosis.
Limitations: Our findings need to be verified in larger and more diverse patient samples before generalization can be made.
Conclusion: The insight obtained in this work can provide guidance to pharmaceutical drug product design and has also the potential to improve patient care through the acknowledgment of patient preferences in clinical practice.
•Control strategy for an offshore wind farm with the generating units connected in series with a VSC-HVDC transmission link.•DC-DC solid-state transformer to interconnected the wind generation units ...of an offshore farm in series with a DC transmission link.•Voltage source converter DC transmission systems for offshore wind farm inter- connection.
This work proposes an air-core DC-DC solid state transformer to connect the wind turbines of an offshore wind farm in series with a DC transmission link. This emerging layout does not use a power transformer to increase the voltage from the offshore collector network to the transmission level, nor does it require a rectifier station to convert the electrical energy to DC. The diode-clamped rectifiers, connected to each permanent-magnet generator, are controlled to drain sinusoidal currents from the generators in order to extract the maximum power from the wind turbines. The air-core transformer, designed by means of a finite element software, ensures the galvanic isolation between the wind generator and the HVDC link. From the generator side, a single-phase full-bridge three-level inverter feeds the primary coil of the transformer, whereas the secondary coil is wound using by means of an XLPE-insulated cable. This paper also presents a strategy for designing the controllers that regulate the output voltage of each wind conversion unit. Results from digital simulations, obtained with PSCAD/EMTDC, are presented to validate the technical feasibility of the proposed DC-DC solid-state transformer scheme, as well as to demonstrate its performance under different operational conditions.
Bacterial cellulose (BC) is a highly pure form of cellulose, produced in the form of a swollen membrane by several bacteria that demonstrated to be able to modulate the skin release of model drugs. ...In the present study, the skin irritation potential of BC was evaluated in human subjects. BC membranes with and without glycerin (acting as plasticizer) were tested. No significant differences were observed for transepidermal water loss (TEWL) measurements in comparison with negative control, 2 and 24h after patch removal, which is an indicator of an absence of barrier disruption. Similar results were found for erythema. Clinical scores were zero at both times for all volunteers, with the exception of five volunteers that exhibited weak reactions. BC with glycerin provided a skin moisturizing effect statistically higher than the negative control (p=0.044), which was not observed for BC alone. The good skin tolerance found after a single application under occlusion reinforces the putative interest of BC membranes as supports for drug topical delivery. Besides modifying the mechanical properties, the inclusion of glycerin results in a skin moisturizing effect which could be clinically relevant for the treatment for skin diseases characterized by dryness, such as psoriasis and atopic dermatitis.
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Several active compounds are sensitive to light, especially to the ultraviolet radiation (UV-R) leading to their degradation or modification, with lost or decrease of their biological ...activity. The aim of this study was to perform a systematic review regarding photostabilization strategies used on health products and perform a critical appraisal of their effectiveness.
The bibliographic search identified 2261 results and merely 40 studies met the selection criteria. Of these, 85% referred to encapsulation strategies, 10% to antioxidants and 5% to the use of solar filters. Cyclodextrins (CD’s) were the most used encapsulation systems (32.5%) followed by liposomes and lipid nanoparticles (each 17.5%), microparticles (15%) and polymeric nanoparticles (10%). The most effective were found to be liposomes and lipid nanoparticles. However, the different methodological conditions used limit the true relevance of this finding.
A gold standard strategy suitable for all compounds cannot be proposed. Instead, case-by-case evaluation, supported on the photodegradation mechanism is recommended. Systematic studies that compare different photostabilization strategies undertaken with the same irradiation conditions are also needed.
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