Infections caused by resistant microorganisms often fail to respond to conventional therapy, resulting in prolonged illness, increased treatment costs and greater risk of death. Consequently, the ...development of novel antimicrobial drugs is becoming more demanding every day since the existing drugs either have too many side-effects or they tend to lose effectiveness due to the selection of resistant strains. In view of these facts, a number of new strategies to obstruct vital biological processes of a microbial cell have emerged; one of these is focused on the use of metal-chelating agents, which are able to selectively disturb the essential metal metabolism of the microorganism by interfering with metal acquisition and bioavailability for crucial reactions. The chelation activity is able to inhibit the biological role of metal-dependent proteins (e.g., metalloproteases and transcription factors), disturbing the microbial cell homeostasis and culminating in the blockage of microbial nutrition, growth and development, cellular differentiation, adhesion to biotic (e.g., extracellular matrix components, cell and/or tissue) and abiotic (e.g., plastic, silicone and acrylic) structures as well as controlling the in vivo infection progression. Interestingly, chelating agents also potentiate the activity of classical antimicrobial compounds. The differences between the microorganism and host in terms of the behavior displayed in the presence of chelating agents could provide exploitable targets for the development of an effective chemotherapy for these diseases. Consequently, metal chelators represent a novel group of antimicrobial agents with potential therapeutic applications. This review will focus on the anti-fungal and anti-protozoan action of the most common chelating agents, deciphering and discussing their mode of action.
Background
Awake prone positioning has been widely used in patients with COVID‐19 respiratory failure to avoid intubation despite limited evidence. Our objective was to evaluate if prone positioning ...is associated with a reduced intubation rate when compared to usual care.
Methods
This was a retrospective cohort study in the emergency department of a large quaternary hospital in Sao Paulo. We retrieved data from all admitted patients in need of oxygen supplementation (>3 L/min) and tachypnea (>24 ipm) from March 1 to April 30, 2020, excluding those who had any contraindication to the prone position or who had an immediate need for intubation. The primary endpoint was endotracheal intubation up to 15 days. Secondary outcomes included a 6‐point clinical outcome ordinal scale, mechanical ventilation–free days, admission to the intensive care unit, and need of hemodialysis and of vasoactive drugs, all assessed at or up to 15 days. We analyzed unadjusted and adjusted effect estimates with Cox proportional hazards models, logistic regression, quantile regression, and sensitivity analyses using propensity score models.
Results
Of 925 suspected COVID‐19 patients admitted off mechanical ventilation, 166 patients fulfilled inclusion and exclusion criteria: 57 were exposed to prone positioning and 109 to usual care. In the intervention group, 33 (58%) were intubated versus 53 (49%) in the control group. We observed no difference in intubation rates in the univariate analysis (hazard ratio = 1.21, 95% confidence interval CI = 0.78 to 1.88, p = 0.39) nor in the adjusted analysis (hazard ratio = 0.90, 95% CI = 0.55 to 1.49, p = 0.69). Results were robust to the sensitivity analyses. Secondary outcomes did not differ between groups.
Conclusions
Awake prone positioning was not associated with lower intubation rates. Caution is necessary before widespread adoption of this technique, pending results of clinical trials.
•A double skin façade (DSF) applied in a test cell is designed and analyzed.•Thermocouples K type is used to measure the temperatures and hot wire anemometers for the air velocity.•Ansys CFX ...simulations are made to obtain a better analysis of heat transfer and airflow.•Results of an uninterrupted 3-day measurement sequence are presented.•Results show that DSF can contribute to the reduction of the temperature of the wall faces and contribute with the reducing of the heat gains in the indoor environment.
This paper investigates the efficiency of a naturally ventilated double-skin façade (DSF) built in a test cell focusing on the airflow and heat convection of the cavity formed by DSF. The study covers measurements of the test cell and their numerical simulation. DSFs have been widely researched worldwide, since they contribute to the thermal performance of the internal environment and to energy savings by eliminating mechanical conditioning systems. For data acquisition, type K surface thermocouples are installed on the wall faces of the test cell and the additional façade, that is, on the inner and outer face of the wall of the test cell and the inner face of the external one. Furthermore, hot wire anemometers are positioned so as to obtain the air velocity in the lower and upper openings of the cavity, which has an air layer thickness of 0.1 m. The results show that the DSF presence contributes to a decrease of the temperature inside the environment because it inhibits the direct solar radiation. Measurement of the faces shows that at 4:00 p.m. the temperature reaches their maximum values. These values are equal to 25.6 °C on the inner face of the façade and 23.6 °C on the inner face of the test cell, while the outdoor temperature presents values equal to 23.1 °C at this time.
Microfluidic paper-based devices (μPADs) and wearable devices have been highly studied to be used as diagnostic tools due to their advantages such as simplicity and ability to provide instrument-free ...fast results. Diseases such as periodontitis and diabetes mellitus can potentially be detected through these devices by the detection of important biomarkers. This study describes the development of μPADs through craft cutter printing for glucose and nitrite salivary diagnostics. In addition, the use of μPADs integrated into a mouthguard as a wearable sensor for glucose monitoring is also presented. μPADs were designed to contain two detection zones for glucose and nitrite assays and a sampling zone interconnected by microfluidic channels. Initially, the analytical performance of the proposed μPADs was investigated and it provided linear behavior (
r
2
≥ 0.994) in the concentration ranges between 0 to 2.0 mmol L
−1
and 0 to 400 μmol L
−1
for glucose and nitrite, respectively. Under the optimized conditions, the limits of detection achieved for glucose and nitrite were 27 μmol L
−1
and 7 μmol L
−1
, respectively. Human saliva samples were collected from healthy individuals and patients previously diagnosed with periodontitis or diabetes and then analyzed on the proposed μPADs. The results found using μPADs revealed higher glucose concentration values in saliva collected from patients diagnosed with diabetes mellitus and greater nitrite concentrations in saliva collected from patients diagnosed with periodontitis, as expected. The results obtained on μPADs did not differ statistically from those measured by spectrophotometry. With the aim of developing paper-based wearable sensors, μPADs were integrated, for the first time, into a silicone mouthguard using a 3D-printed holder. The proof of concept was successfully demonstrated through the monitoring of the glucose concentration in saliva after the ingestion of chocolate. According to the results reported herein, paper-based microfluidic devices offer great potential for salivary diagnostics, making their integration into a silicone mouthguard possible, generating simple, low-cost, instrument-free, and powerful wearable sensors.
Mucositis is an inflammation of the gastrointestinal mucosa resulting from high doses of radio/chemotherapy treatment and may lead to interruption of antineoplasic therapy. Soluble fibres, like ...pectin, increase SCFA production, which play a role in gut homoeostasis and inflammation suppression. Due to the properties of pectin, the aim of the present study was to evaluate the effect of a high-fibre (HF) diet on chemotherapy-induced mucositis in a murine model. C57/BL6 mice received control (AIN93M), HF, low/zero fibre (LF) diets for 10 d prior to mucositis challenging with irinotecan (75 mg/kg), or they were treated with acetate added to drinking water 5 d prior to and during the mucositis induction. Mice that received the HF diet showed decreased immune cells influx and improved histopathological parameters in the intestine, compared with mice that received the normal diet. Furthermore, the HF diet decreased intestinal permeability induced in the mucositis model when compared with the control group. This effect was not observed for acetate alone, which did not improve gut permeability. For instance, mice that received the LF diet had worsened gut permeability, compared with mice that received the normal diet and mucositis. The effects of the HF and LF diets were shown to modulate the intestinal microbiota, in which the LF diet increased the levels of Enterobacteriaceae, a group associated with gut inflammation, whereas the HF diet decreased this group and increased Lactobacillus and Bifidobacterium (SCFA producers) levels. In conclusion, the results demonstrated the importance of dietary fibre intake in the modulation of gut microbiota composition and homoeostasis maintenance during mucositis in this model.
We present a benchmark investigation on the O-H bond dissociation enthalpies (BDEs) and ionization potential (IP) for gallic acid (GA), a widely known polyphenolic antioxidant. These properties were ...determined in the gas-phase and in water through the use of density functional theory (DFT), second-order Møller-Plesset perturbation theory (MP2), coupled-cluster with single and double excitations (CCSD), and coupled-cluster with single and double excitations as well as perturbative inclusion of triples (CCSD(T)). The 6-311++G(df,p), cc-pVDZ, aug-cc-pVDZ, cc-pVTZ, and aug-cc-pVTZ basis sets were used. Regarding DFT functionals, the M06-2X provided the best agreement for the BDEs when compared to the corresponding CCSD(T)/aug-cc-pVTZ results; M06-2X was also found to be the most suitable for probing the IP for the protonated forms of GA while LC-ωPBE was the most reliable in the case of deprotonated GA. Given that these properties represent important descriptors for examining mechanisms related to the antioxidant potential of a given polyphenol, we hope that the present work can serve as a guide for computational chemists venturing in the field.
Astrocytes can adopt multiple molecular phenotypes in the brain of Alzheimer's disease (AD) patients. Here, we studied the associations of cerebrospinal fluid (CSF) glial fibrillary acidic protein ...(GFAP) and chitinase-3-like protein 1 (YKL-40) levels with brain amyloid-β (Aβ) and tau pathologies. We assessed 121 individuals across the aging and AD clinical spectrum with positron emission tomography (PET) brain imaging for Aβ (
FAZD4694) and tau (
FMK-6240), as well as CSF GFAP and YKL-40 measures. We observed that higher CSF GFAP levels were associated with elevated Aβ-PET but not tau-PET load. By contrast, higher CSF YKL-40 levels were associated with elevated tau-PET but not Aβ-PET burden. Structural equation modeling revealed that CSF GFAP and YKL-40 mediate the effects of Aβ and tau, respectively, on hippocampal atrophy, which was further associated with cognitive impairment. Our results suggest the existence of distinct astrocyte biomarker signatures in response to brain Aβ and tau accumulation, which may contribute to our understanding of the complex link between reactive astrogliosis heterogeneity and AD progression.
The synthesis of the first bismuth‐containing macromolecules that exhibit phosphorescence in the solid state and in the presence of oxygen is reported. These red emissive high molecular weight ...polymers (>300 kDa) feature benzobismoles appended to a hydrocarbon scaffold, and were built via an efficient ring‐opening metathesis (ROMP) protocol. Moreover, our general procedure readily allows for the formation of cross‐linked networks and block copolymers. Attaining stable red phosphorescence with non‐toxic elements remains a challenge and, thus, our new class of soluble (processable) polymeric phosphor is of great interest. Furthermore, the formation of bismuth‐rich cores within organic–inorganic block copolymer spherical micelles is possible, leading to patterned arrays of bismuth in the film state.
Turning on Bismuth: The synthesis of red and orange emitting bismuth‐based phosphors is reported. The modular synthetic approach allows for rapid ring‐opening metathesis polymerization to yield block copolymer spherical micelles that assemble into organized films with bismuth‐rich, metallized domains.
In this work, ground and excited-state properties were used as descriptors for probing mechanisms as well as to assess potential alternatives for tackling the elimination of perfluorobutane sulfonic ...acid (PFBS) - C
4
F
9
SO
2
OH, perfluorooctane sulfonic acid (PFOS) - C
8
F
17
SO
2
OH, and perfluorooctanoic acid (PFOA) - C
7
F
15
COOH. For this purpose, density functional theory (DFT) and its time-dependent formalism (TD-DFT) at both CAM-B3LYP/6-311+G(2d,2p) and M06-2X/6-311+G(2d,2p) levels of theory in water (IEF-PCM) were employed. To gauge the accuracy of the DFT approaches for the current systems, wave function methods (Møller-Plesset, MP2, coupled-cluster with single and double excitations, CCSD, CCSD with perturbative triples, CCSD(T), and equation of motion CCSD, EOM-CCSD) and aug-cc-pVXZ (X = D and T) basis sets were used. Regarding PFBS and PFOS, all the excited states probed were found to be energetically accessible only in the high-energy vacuum UV region (<200 nm ≥6.20 eV); SO
2
O
−
is released when the first low-lying excited singlet state (2
1
A) of both compounds is accessed. On the other hand, two lowest-lying excited singlet states of PFOA were computed at considerably lower energy (5.84 eV and 5.97 eV for 2
1
A and 3
1
A, respectively, at the TD-DFT/CAM-B3LYP/6-311+G(2d,2p)). In addition, intramolecular OH radical formation is suggested for protonated PFOA when interacting with radiation at 7.98 eV 155 nm, as determined at the TD-DFT/CAM-B3LYP/6-311+G(2d,2p) level of theory. Such intramolecularly generated hydroxyl may contribute to a faster degradation of PFOA (or of other per- and poly-fluoroalkyl substances (PFAS) that are usually found together with PFOA).
In this work, ground and excited-state properties were used as descriptors for probing mechanisms as well as to assess potential alternatives for tackling the elimination of per- and poly-fluoroalkyl substances (PFAS).
Large admission DWI lesion volumes are associated with poor outcomes despite acute stroke treatment. The primary aims of our study were to determine whether CTA collaterals correlate with admission ...DWI lesion volumes in patients with AIS with proximal occlusions, and whether a CTA collateral profile could identify large DWI volumes with high specificity.
We studied 197 patients with AIS with M1 and/or intracranial ICA occlusions. We segmented admission and follow-up DWI lesion volumes, and categorized CTA collaterals by using a 5-point CS system. ROC analysis was used to determine CS accuracy in predicting DWI lesion volumes >100 mL. Patients were dichotomized into 2 categories: CS = 0 (malignant profile) or CS>0. Univariate and multivariate analyses were performed to compare imaging and clinical variables between these 2 groups.
There was a negative correlation between CS and admission DWI lesion volume (ρ = -0.54, P < .0001). ROC analysis revealed that CTA CS was a good discriminator of DWI lesion volume >100 mL (AUC = 0.84, P < .001). CS = 0 had 97.6% specificity and 54.5% sensitivity for DWI volume >100 mL. CS = 0 patients had larger mean admission DWI volumes (165.8 mL versus 32.7 mL, P < .001), higher median NIHSS scores (21 versus 15, P < .001), and were more likely to become functionally dependent at 3 months (95.5% versus 64.0%, P = .003). Admission NIHSS score was the only independent predictor of a malignant CS (P = .007).
In patients with AIS with PAOs, CTA collaterals correlate with admission DWI infarct size. A malignant collateral profile is highly specific for large admission DWI lesion size and poor functional outcome.
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