Bloodstream infections remain a major cause of morbidity and mortality. Gram-negative bacilli (GNB) bacteremia is typically transient and usually resolves rapidly after the initiation of appropriate ...antibiotic therapy and source control. The optimal duration of treatment and utility of follow-up blood cultures (FUBC) have not been studied in detail. Currently, the management of gram-negative bacteremia is determined by clinical judgment. To investigate the value of repeat blood cultures, we analyzed 500 episodes of bacteremia to determine frequency of FUBC and identify risk factors for persistent bacteremia.
Of 500 episodes of bacteremia, we retrospectively analyzed 383 (77%) that had at least 1 FUBC. We sought information regarding presumed source of bacteremia, antibiotic status at the time of FUBC, antibiotic susceptibility, presence of fever, comorbidities (intravenous central lines, urinary catheters, diabetes mellitus, AIDS, end-stage renal disease, and cirrhosis), need for intensive care, and mortality.
Antibiotic use did not affect the rate of positivity of FUBC, unless bacteria were not sensitive to empiric antibiotic. Fever on the day of FUBC was associated with higher rates of positive FUBC for gram-positive cocci (GPC) but not GNB. Mortality and care in the intensive care unit were not associated with positive FUBC. Seventeen FUBC and 5 FUBC were drawn for GNB and GPC to yield 1 positive result.
FUBC added little value in the management of GNB bacteremia. Unrestrained use of blood cultures has serious implications for patients including increased healthcare costs, longer hospital stays, unnecessary consultations, and inappropriate use of antibiotics.
Emicizumab: the hemophilia A game-changer Alcedo Andrade, Pedro E; Mannucci, Pier Mannuccio; Kessler, Craig M
Haematologica (Roma),
05/2024, Letnik:
109, Številka:
5
Journal Article
Recenzirano
Odprti dostop
In hemophilia, the unmet needs regarding adherence to prophylaxis and lack of effective long-term prophylaxis regimens, especially in patients with inhibitors, led to the production of emicizumab, ...the first non-factor medicine for subcutaneous administration in patients with severe and moderate hemophilia A with or without factor VIII inhibitors. This review describes the research steps behind the development of this game-changing medication as well as its success in the prophylaxis of bleeding episodes, as witnessed by the results of pivotal clinical trials but also by real-life use in the frame of a still expanding global market. We also discuss potential and actual adverse events and the nuances related to clinical use, such as laboratory monitoring, development of neutralizing antidrug antibodies, risk of thrombosis/hypercoagulability and role in the management of surgical operations. The potential of emicizumab to prevent bleeding in other congenital and acquired coagulation disorders is also outlined.
Many works reported the encapsulation of iodine in metal–organic frameworks as well as the I2 → I3 – chemical conversion. This transformation has been examined by adsorbing gaseous iodine on a series ...of UiO-66 materials and the different Hf/Zr metal ratios (0–100% Hf) were evaluated during the evolution of I2 into I3 –. The influence of the hafnium content on the UiO-66 structure was highlighted by PXRD, SEM images, and gas sorption tests. The UiO-66(Hf) presented smaller lattice parameter (a = 20.7232 Å), higher crystallite size (0.18 ≤ Φ ≤ 3.33 μm), and smaller SSABET (818 m2·g–1) when compared to its parent UiO-66(Zr) a = 20.7696 Å, 100 ≤ Φ ≤ 250 nm, and SSABET = 1262 m2·g–1. The effect of replacing Zr atoms by Hf in the physical properties of the UiO-66 was deeply evaluated by a spectroscopic study using UV–vis, FTIR, and Raman characterizations. In this case, the Hf presence reduced the band gap of the UiO-66, from 4.07 eV in UiO-66(Zr) to 3.98 eV in UiO-66(Hf). Furthermore, the UiO-66(Hf) showed a blue shift for several FTIR and Raman bands, indicating a stiffening on the implied interatomic bonds when comparing to UiO-66(Zr) spectra. Hafnium was found to clearly favor the capture of iodine 285 g·mol–1, against 230 g·mol–1 for UiO-66(Zr) and the kinetic evolution of I2 into I3 – after 16 h of I2 filtration. Three iodine species were typically identified by Raman spectroscopy and chemometric analysis. These species are as follows: “free” I2 (206 cm–1), “perturbed” I2 (173 cm–1), and I3 – (115 and 141 cm–1). It was also verified, by FTIR spectroscopy, that the oxo and hydroxyl groups of the inorganic M6O4(OH)4 (M = Zr, Hf) cluster were perturbed after the adsorption of I2 into UiO-66(Hf), which was ascribed to the higher acid character of Hf. Finally, with that in mind and considering that the EPR results discard the possibility of a redox phenomenon involving the tetravalent cations (Hf4+ or Zr4+), a mechanism was proposed for the conversion of I2 into I3 – in UiO-66based on an electron donor–acceptor complex between the aromatic ring of the BDC linker and the I2 molecule.
Metal–organic frameworks (MOFs) have been largely investigated worldwide for their use in the capture of radioactive iodine due to its potential release during nuclear accident events and ...reprocessing of nuclear fuel. The present work deals with the capture of gaseous I2 under a continuous flow and its subsequent transformation into I3 – within the porous structures of three distinct, yet structurally related, terephthalate-based MOFs: MIL-125(Ti), MIL-125(Ti)_NH2, and CAU-1(Al)_NH2. The synthesized materials exhibited specific surface areas (SSAs) with similar order of magnitude: 1207, 1099, and 1110 m2 g–1 for MIL-125(Ti), MIL-125(Ti)_NH2, and CAU-1(Al)_NH2, respectively. Because of that, it was possible to evaluate the influence of other variables over the iodine uptake capacitysuch as band gap energies, functional groups, and charge transfer complexes (CTC). After 72 h of contact with the I2 gas flow, MIL-125(Ti)_NH2 was able to trap 11.0 mol mol–1 of I2, followed by MIL-125(Ti) (8.7 mol mol–1), and by CAU-1(Al)_NH2 (4.2 mol mol–1). The enhanced ability to retain I2 in the MIL-125(Ti)_NH2 was associated with a combined effect between its amino group (which has a great affinity toward iodine), its smaller band gap (2.5 eV against 2.6 and 3.8 eV for CAU-1(Al)_NH2 and MIL-125(Ti), respectively), and its efficient charge separation. In fact, the presence of a linker-to-metal charge transfer (LMCT) mechanism in MIL-125(Ti) compounds separates the photogenerated electrons and holes into the two distinct moieties of the MOF: the organic linker (which stabilizes the holes) and the oxy/hydroxy inorganic cluster (which stabilizes the electrons). This effect was observed using EPR spectroscopy, whereas the reduction of the Ti4+ cations into the paramagnetic Ti3+ species was evidenced after irradiation of the pristine Ti-based MOFs with UV light (<420 nm). In contrast, because CAU-1(Al)_NH2 exhibits a purely linker-based transition (LBT)with no EPR signals related to Al paramagnetic speciesit tends to exhibit faster recombination of the photogenerated charge carriers as, in this case, both electrons and holes are located over the organic linker. Furthermore, the transformation of the gaseous I2 into I n – n = 5, 7, 9, ... intermediates and then into I3 – species was evaluated using Raman spectroscopy by following the evolution of their respective bands at about 198, 180, and 113 cm–1. This conversionwhich is favored by an effective charge separation and smaller band gapsincreases the I2 uptake capacity of the compounds by creating specific adsorption sites for these anionic species. In fact, because the −NH2 groups act as an antenna to stabilize the photogenerated holes, both I n – and I3 – are adsorbed into the organic linker via an electrostatic interaction with these positively charged entities. Finally, changes regarding the EPR spectra before and after the iodine loading were considered to propose a mechanism for the electron transfer from the MOFs structure to the I2 molecules considering their different characteristics.
The main sulfate-reducing (SRB) and sulfur-oxidizing bacteria (SOB) in six wastewater treatment plants (WWTPs) located at southern Brazil were described based on high-throughput sequencing of the 16S ...rDNA. Specific taxa of SRB and SOB were correlated with some abiotic factors, such as the source of the wastewater, oxygen content, sample type, and physical chemical attributes of these WWTPs. When the 22 families of SRB and SOB were clustered together, the samples presented a striking distribution, demonstrating grouping patterns according to the sample type. For SOB, the most abundant families were
Spirochaetaceae
,
Chromatiaceae
,
Helicobacteriaceae
,
Rhodospirillaceae
, and
Neisseriaceae
, whereas, for SRB, were
Syntrophaceae
,
Desulfobacteraceae
,
Nitrospiraceae
, and
Desulfovibriaceae
. The structure and composition of the major families related to the sulfur cycle were also influenced by six chemical attributes (sulfur, potassium, zinc, manganese, phosphorus, and nitrogen). Sulfur was the chemical attribute that most influenced the variation of bacterial communities in the WWTPs (
λ
= 0.14,
p
= 0.008). The OTUs affiliated to
Syntrophus
showed the highest response to the increase of total sulfur. All these findings can contribute to improve the understanding in relation to the sulfur-oxidizing and sulfate-reducing communities in WWTPs aiming to reduce H
2
S emissions.
The adsorption of DCB in MZSM-5 (M = H+, Na+) and silicalite-1 channel zeolites takes place without chemical or structural modification of the zeolite. Upon UV photoexcitation, a radical anion - hole ...pair is stabilized as demonstrated by time resolved diffuse reflectance UV–visible spectroscopy. The photogeneration of the radical anion DCBradical dot- is assigned to the dual (ambivalent) role of the zeolite framework as electron donor and hole stabilizator. The observation of such electron transfer only in the aluminated zeolite highlights the key role of the aluminum and of charge balancing cations. By studying the recombination of the radical anion – hole pairs at different temperature, the activation energy has been determined as a function of the nature of the charge-balancing cation. The values of the free enthalpy have been calculated using the Marcus theory from which the local redox potential of the zeolite has been estimated.
Organic pollutants have been a significant source of concern in recent years due to their facile dissemination and harmful effects. In this work, two different metal–organic frameworks (MOFs) were ...initially prepared by hydrothermal treatment, namely aluminum trimesate (MIL-100(Al)) and copper trimesate (HKUST-1). These materials were subsequently submitted to a post-synthetic modification step to grow titania nanoparticles on their surface. Anatase nanoparticles with sizes around 5 nm were successfully anchored on MIL-100(Al), and the concentration of TiO
2
in this sample was about 68 wt.%. This is the first time that this composite (TiO
2
@MIL-100(Al)) is reported in the literature. It showed an improved photocatalytic activity, removing 90% of methylene blue (
k
app
= 1.29 h
−1
), 55% of sodium diclofenac (
k
app
= 0.21 h
−1
), and 62% of ibuprofen (
k
app
= 0.37 h
−1
) after four hours of illumination with UV-A light. A significant concentration (14 µM) of reactive oxygen species (ROS) was detected for this composite. HKUST-1 showed a structural collapse during its post-synthetic modification, leading to a non-porous material and providing fewer sites for the heterogeneous nucleation of titania. This behavior led to a low concentration of rutile nanoparticles on HKUST-1 (9 wt.%). However, the obtained composite (TiO
2
@HKUST) also showed an improved photoactivity compared to HKUST-1, increasing the photodegradation rates evaluated for methylene blue (0.05 h
−1
vs. 0.29 h
−1
), sodium diclofenac (negligible vs. 0.03 h
−1
), and ibuprofen (0.01 h
−1
vs. 0.02 h
−1
). This work brings new insights concerning the preparation of photocatalysts by growing semiconductor nanoparticles on trimesate-based MOFs.
Tumor antigen-specific monoclonal antibodies (mAb) block oncogenic signaling and induce Fcγ receptor (FcγR)-mediated cytotoxicity. However, the role of CD8(+) CTL and FcγR in initiating innate and ...adaptive immune responses in mAb-treated human patients with cancer is still emerging.
FcγRIIIa codon 158 polymorphism was correlated with survival in 107 cetuximab-treated patients with head and neck cancer (HNC). Flow cytometry was carried out to quantify EGF receptor (EGFR)-specific T cells in cetuximab-treated patients with HNC. The effect of cetuximab on natural killer (NK) cell, dendritic cell (DC), and T-cell activation was measured using IFN-γ release assays and flow cytometry.
FcγRIIIa polymorphism did not predict clinical outcome in cetuximab-treated patients with HNC; however, elevated circulating EGFR(853-861)-specific CD8(+) T cells were found in cetuximab-treated patients with HNC (P < 0.005). Cetuximab promoted EGFR-specific cellular immunity through the interaction of EGFR(+) tumor cells and FcγRIIIa on NK cells but not on the polymorphism per se. Cetuximab-activated NK cells induced IFN-γ-dependent expression of DC maturation markers, antigen processing machinery components such as TAP-1/2 and T-helper cell (T(H)1) chemokines through NKG2D/MICA binding. Cetuximab initiated adaptive immune responses via NK cell-induced DC maturation, which enhanced cross-presentation to CTL specific for EGFR as well as another tumor antigen, MAGE-3.
Cetuximab-activated NK cells promote DC maturation and CD8(+) T-cell priming, leading to tumor antigen spreading and TH1 cytokine release through "NK-DC cross-talk." FcγRIIIa polymorphism did not predict clinical response to cetuximab but was necessary for NK-DC interaction and mAb-induced cross-presentation. EGFR-specific T cells in cetuximab-treated patients with HNC may contribute to clinical response.
Electron transfer (ET) processes are of fundamental importance in many photochemical processes in biological and chemical systems. Here, semiconductor nanoparticles of ZnS (as electron relay) and ...trans-stilbene molecules (t-St) (as electron donor), both confined within the porous volume of mordenite (MOR), are combined to mimic photosynthetic processes. ZnS nanoparticles were synthesized by cationic exchange between the counterion of the zeolite and ZnS precursors in solution. The characterization of the ZnS/Na-MOR composite was performed by powder X-ray diffraction (XRD), diffuse reflectance UV–vis spectroscopy, X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM) coupled with energy-dispersive X-ray spectroscopy (EDS). These complementary techniques highlight the successful formation of ZnS nanoparticles at the surface of Na-MOR. The electron transfer mechanisms taking place after the incorporation and photoionization of t-St molecules were evaluated using diffuse reflectance UV–vis spectroscopy. The results show the formation of long-lived t-St•+@ZnS/Na-MOR•– charge-separated states (lifetime = 18 min; k = 0.0553 min–1) whose stability is linked to the nature of the new charge compensating cation and to the close proximity of the ZnS nanoparticles, which are probably located within the zeolite framework. Indeed, the augmentation of the transient species lifetime was attributed to an electron transfer from the t-St molecule toward the ZnS conduction band.
In recent decades, sociologist Ulrich Beck (1992) has been warning about the risk society in which we operate today, which includes risks that are not only conjunctural but essentially structural, ...such as pollution and global warming. Recently, contemporaneity faces a new serious risk, the pandemic caused by COVID-19, which seems to be transforming our social formations into a viral society. In order to understand these social processes and sociological questions, the present text draws attention to one of the most relevant social and intercultural mediations in the current social framework, the articulation between the coronavirus pandemic and tourist activities. A case study deals here with the discourse produced about such themes by digital social network Wikipedia. This study is contextualized by theoretical and practical reflections from tourism studies and supported by ideas such as “viral risk” and “viral risk tourism”. A sample of content extracted from Wikipedia is analyzed and interpreted through a qualitative and quantitative method developed by the author, named “hybrid discourse analysis”, which uses, among other interpretive tools, the “alphabet of interconceptual relations”.
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