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Clinical Nephrology Aug 2023Atypical hemolytic uremic syndrome (aHUS) is a genetic-based thrombotic microangiopathy (TMA) that is mediated by the activation of the alternative complement pathway....
PURPOSE
Atypical hemolytic uremic syndrome (aHUS) is a genetic-based thrombotic microangiopathy (TMA) that is mediated by the activation of the alternative complement pathway. Heterozygous deletion in CFHR3-CFHR1 occurs in 30% of the general population and has not been classically linked to aHUS. Post-transplant aHUS has been associated with a high rate of graft loss. Herein, we report our case series of patients who developed aHUS after solid-organ transplantation.
MATERIALS AND METHODS
Five consecutive cases of post-transplant aHUS were identified at our center. Genetic testing was performed in all but one.
RESULTS
One patient had a presumed TMA diagnosis before transplant. One heart and 4 kidney (KTx) transplant recipients were diagnosed with aHUS based on the clinical picture of TMA, acute kidney injury, and normal ADAMTS13 activity. Genetic mutation testing revealed heterozygous deletion in CFHR3-CFHR1 in 2 patients and a heterozygous complement factor I (CFI) variant of uncertain clinical significance (VUCS) (Ile416Leu) in a third. Four patients were on tacrolimus, 1 had anti-HLA-A68 donor-specific antibody (DSA), and another had borderline acute cellular rejection at the time of aHUS diagnosis. Four responded to eculizumab, and 1 out of 2 patients came off renal replacement therapy. One KTx recipient died from severe bowel necrosis in the setting of early post-transplant aHUS.
CONCLUSION
Calcineurin inhibitors, rejection, DSA, infections, surgery, and ischemia-reperfusion injury are common triggers that could unmask aHUS in solid-organ transplant recipients. Heterozygous deletion in CFHR3-CFHR1 and CFI VUCS may be important susceptibility factors acting as the first hit for alternative complement pathway dysregulation.
Topics: Humans; Atypical Hemolytic Uremic Syndrome; Mutation; Tacrolimus; Thrombotic Microangiopathies; Kidney Transplantation; Antilymphocyte Serum
PubMed: 37288831
DOI: 10.5414/CN111160 -
International Journal of Molecular... Apr 2024In response to cellular metabolic and signaling cues, the mitochondrial network employs distinct sets of membrane-shaping factors to dynamically modulate organellar... (Review)
Review
In response to cellular metabolic and signaling cues, the mitochondrial network employs distinct sets of membrane-shaping factors to dynamically modulate organellar structures through a balance of fission and fusion. While these organellar dynamics mediate mitochondrial structure/function homeostasis, they also directly impact critical cell-wide signaling pathways such as apoptosis, autophagy, and the integrated stress response (ISR). Mitochondrial fission is driven by the recruitment of the cytosolic dynamin-related protein-1 (DRP1), while fusion is carried out by mitofusins 1 and 2 (in the outer membrane) and optic atrophy-1 (OPA1) in the inner membrane. This dynamic balance is highly sensitive to cellular stress; when the transmembrane potential across the inner membrane (Δψ) is lost, fusion-active OPA1 is cleaved by the overlapping activity with m-AAA protease-1 (OMA1 metalloprotease, disrupting mitochondrial fusion and leaving dynamin-related protein-1 (DRP1)-mediated fission unopposed, thus causing the collapse of the mitochondrial network to a fragmented state. OMA1 is a unique regulator of stress-sensitive homeostatic mitochondrial balance, acting as a key upstream sensor capable of priming the cell for apoptosis, autophagy, or ISR signaling cascades. Recent evidence indicates that higher-order macromolecular associations within the mitochondrial inner membrane allow these specialized domains to mediate crucial organellar functionalities.
Topics: Mitochondrial Dynamics; Humans; Homeostasis; Animals; Mitochondria; Stress, Physiological; Mitochondrial Proteins; Metalloendopeptidases; Signal Transduction; Autophagy; Dynamins; Apoptosis; GTP Phosphohydrolases
PubMed: 38674151
DOI: 10.3390/ijms25084566 -
EFSA Journal. European Food Safety... Jul 2023The conclusions of EFSA following the peer review of the initial risk assessments carried out by the Assessment Group on Glyphosate (AGG), consisting of the competent... (Review)
Review
The conclusions of EFSA following the peer review of the initial risk assessments carried out by the Assessment Group on Glyphosate (AGG), consisting of the competent authorities of France, the Netherlands, Sweden and Hungary, acting jointly as rapporteur Member State for the pesticide active substance glyphosate are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative uses of glyphosate as a herbicide as proposed by the applicants, covering uses pre-sowing, pre-planting and pre-emergence plus post-harvest in vegetables and sugar beet; post-emergence of weeds in orchards, vineyards, row vegetables, railway tracks against emerged annual, biennial and perennial weeds. Moreover, uses as spot treatment against invasive species in agricultural and non-agricultural areas, and in vegetables and sugar beet against couch grass are also included. The reliable endpoints, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.
PubMed: 37502013
DOI: 10.2903/j.efsa.2023.8164 -
Advanced Materials (Deerfield Beach,... Sep 2023Surface acoustic waves (SAW) provide a promising platform to study spin-phonon coupling, which can be achieved by SAW-driven ferromagnetic resonance (FMR) for efficient...
Surface acoustic waves (SAW) provide a promising platform to study spin-phonon coupling, which can be achieved by SAW-driven ferromagnetic resonance (FMR) for efficient acoustic manipulation of spin. Although the magneto-elastic effective field model has achieved great success in describing SAW-driven FMR, the magnitude of the effective field acting on the magnetization induced by SAW still remains hard to access. Here, by integrating ferromagnetic stripes with SAW devices, direct-current detection for SAW-driven FMR based on electrical rectification is reported. By analyzing FMR rectified voltage, the effective fields are straightforwardly characterized and extracted, which exhibits the advantages of better integration compatibility and lower cost than traditional methods such as vector-network analyzer-based techniques. A large nonreciprocal rectified voltage is obtained, which is attributed to the coexistence of in-plane and out-of-plane effective fields. The effective fields can be modulated by controlling the longitudinal and shear strains within the films to achieve almost 100% nonreciprocity ratio, demonstrating the potential for electrical switches. Besides its fundamental significance, this finding provides a unique opportunity for a designable spin acousto-electronic device and its convenient signal readout.
PubMed: 37306652
DOI: 10.1002/adma.202302454 -
Molecular and Cellular Biochemistry Jul 2023Epithelial-to-mesenchymal transition (EMT), which plays an essential role in development, tissue repair and fibrosis, and cancer progression, is a reversible cellular... (Review)
Review
Epithelial-to-mesenchymal transition (EMT), which plays an essential role in development, tissue repair and fibrosis, and cancer progression, is a reversible cellular program that converts epithelial cells to mesenchymal cell states characterized by motility-invasive properties. The mostly signaling pathways that initiated and controlled the EMT program are regulated by a solitary, non-motile organelle named primary cilium. Acting as a signaling nexus, primary cilium dynamically concentrates signaling molecules to respond to extracellular cues. Recent research has provided direct evidence of connection between EMT and primary ciliogenesis in multiple contexts, but the mechanistic understanding of this relationship is complicated and still undergoing. In this review, we describe the current knowledge about the ciliary signaling pathways involved in EMT and list the direct evidence that shows the link between them, trying to figure out the intricate relationship between EMT and primary ciliogenesis, which may aid the future development of primary cilium as a novel therapeutic approach targeted to EMT.
PubMed: 37490178
DOI: 10.1007/s11010-023-04817-w -
Environmental Science and Pollution... Nov 2023Masks are face coverings that give protection from infectious agents, airborne pathogens, bacteria, viruses, surgical fog, dust, and other chemical hazards by acting as... (Review)
Review
Masks are face coverings that give protection from infectious agents, airborne pathogens, bacteria, viruses, surgical fog, dust, and other chemical hazards by acting as a barrier between the wearer and the environment. In the COVID-19 pandemic, this major personal protective equipment's became essential part of our daily life. The aim of this review is to analyze and discuss the different types of masks with their pros and cons, manufacturing procedures, evaluation criteria, and application with some of the sterilization process for reuse and smart mask. The review used a thorough examination of the literature to analyze the preventive effects of surgical, N95, smart mask, and potential environmental damage from those masks. Several studies and evidence were also examined to understand the efficiency of different mask on different environment. N95 respirators are capable of filtering out non-oil-based 95% air-born particles, and surgical masks act as a protective barrier between the wearer and the environment. The application of spoon bond and melt blown techniques in the fabrication process of those masks improves their protective nature and makes them lightweight and comfortable. But the high demand and low supply forced users to reuse and extend their use after sterilizations, even though those masks are recommended to be used once. Universal masking in the SARS-COV-2 pandemic increased the chance of environmental pollution, so the application of smart masks became essential because of their high protection power and self-sterilizing and reusing capabilities.
PubMed: 37968481
DOI: 10.1007/s11356-023-30460-5 -
Polymers Sep 2023Several analytical methods for the fiber pull-out test have been developed to evaluate the bond strength of fiber-matrix systems. We aimed to investigate the debonding...
BACKGROUND
Several analytical methods for the fiber pull-out test have been developed to evaluate the bond strength of fiber-matrix systems. We aimed to investigate the debonding mechanism of a fiber-silicone pull-out specimen and validate the experimental data using 3D-FEM and a cohesive element approach.
METHODS
A 3D model of a fiber-silicone pull-out testing specimen was established by pre-processing CT images of the typical specimen. The materials on the scans were posted in three different cross-sectional views using ScanIP and imported to ScanFE in which 3D generation was implemented for all of the image slices. This file was exported in FEA format and was imported in the FEA software (PATRAN/ABAQUS, version r2) for generating solid mesh, boundary conditions, and material properties attribution, as well as load case creation and data processing.
RESULTS
The FEM cohesive zone pull-out force versus displacement curve showed an initial linear response. The Von Mises stress concentration was distributed along the fiber-silicone interface. The damage in the principal stresses' directions S11, S22, and S33, which represented the maximum possible magnitude of tensile and compressive stress at the fiber-silicone interface, showed that the stress is higher in the direction S33 (stress acting in the Z-direction) in which the lower damage criterion was higher as well when compared to S11 (stress acting in the XY plane) and S23 (stress acting in the YZ plane).
CONCLUSIONS
The comparison between the experimental values and the results from the finite element simulations show that the proposed cohesive zone model accurately reproduces the experimental results. These results are considered almost identical to the experimental observations about the interface. The cohesive element approach is a potential function that takes into account the shear effects with many advantages related to its ability to predict the initiation and progress of the fiber-silicone debonding during pull-out tests. A disadvantage of this approach is the computational effort required for the simulation and analysis process. A good understanding of the parameters related to the cohesive laws is responsible for a successful simulation.
PubMed: 37765521
DOI: 10.3390/polym15183668 -
European Journal of Anaesthesiology Sep 2023Liposomal bupivacaine is claimed by the manufacturer to provide analgesia for up to 72 h postoperatively. (Meta-Analysis)
Meta-Analysis
The postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve and field blocks: A systematic review and meta-analysis, with trial sequential analysis.
BACKGROUND
Liposomal bupivacaine is claimed by the manufacturer to provide analgesia for up to 72 h postoperatively.
OBJECTIVES
To compare the postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve or field blocks.
DESIGN
A systematic review and meta-analysis with trial sequential analysis.
DATA SOURCES
MEDLINE, Embase and Web of Science, among others, up to June 2022.
ELIGIBILITY CRITERIA
We retrieved randomised controlled trials comparing liposomal bupivacaine versus bupivacaine, levobupivacaine or ropivacaine for peripheral nerve and field blocks after all types of surgery. Our primary endpoint was rest pain score (analogue scale 0 to 10) at 24 h. Secondary endpoints included rest pain score at 48 and 72 h, and morphine consumption at 24, 48 and 72 h.
RESULTS
Twenty-seven trials including 2122 patients were identified. Rest pain scores at 24 h were significantly reduced by liposomal bupivacaine with a mean difference (95% CI) of -0.9 (-1.4 to -0.4), I2 = 87%, P < 0.001. This reduction in pain scores persisted at 48 h and 72 h with mean differences (95% CI) of -0.7 (-1.1 to -0.3), I2 = 82%, P = 0.001 and -0.7 (-1.1 to -0.3), I2 = 80%, P < 0.001, respectively. There were no differences in interval morphine consumption at 24 h ( P = 0.15), 48 h ( P = 0.15) and 72 h ( P = 0.07). The quality of evidence was moderate.
CONCLUSIONS
There is moderate level evidence that liposomal bupivacaine reduces rest pain scores by 0.9 out of 10 units, when compared with long-acting local anaesthetics at 24 hours after surgery, and by 0.7 up to 72 hours after surgery.
Topics: Humans; Anesthetics, Local; Pain, Postoperative; Bupivacaine; Analgesics; Morphine; Peripheral Nerves; Analgesics, Opioid
PubMed: 37038770
DOI: 10.1097/EJA.0000000000001833 -
ACS Applied Materials & Interfaces Jul 2023Bacterial biofilms are communities of cells adhered to surfaces. These communities represent a predominant form of bacterial life on Earth. A defining feature of a...
Bacterial biofilms are communities of cells adhered to surfaces. These communities represent a predominant form of bacterial life on Earth. A defining feature of a biofilm is the three-dimensional extracellular polymer matrix that protects resident cells by acting as a mechanical barrier to the penetration of chemicals, such as antimicrobials. Beyond being recalcitrant to antibiotic treatment, biofilms are notoriously difficult to remove from surfaces. A promising, but relatively underexplored, approach to biofilm control is to disrupt the extracellular polymer matrix by enabling penetration of particles to increase the susceptibility of biofilms to antimicrobials. In this work, we investigate externally imposed chemical gradients as a mechanism to transport polystyrene particles into bacterial biofilms. We show that preconditioning the biofilm with a prewash step using deionized (DI) water is essential for altering the biofilm so it takes up the micro- and nanoparticles by the application of a further chemical gradient created by an electrolyte. Using different particles and chemicals, we document the transport behavior that leads to particle motion into the biofilm and its further reversal out of the biofilm. Our results demonstrate the importance of chemical gradients in disrupting the biofilm matrix and regulating particle transport in crowded macromolecular environments, and suggest potential applications of particle transport and delivery in other physiological systems.
Topics: Biofilms; Anti-Bacterial Agents; Extracellular Polymeric Substance Matrix; Anti-Infective Agents; Polymers
PubMed: 37400078
DOI: 10.1021/acsami.3c03190 -
International Journal of Legal Medicine May 2024Synthetic cannabinoids become increasingly popular as a supposedly safe and legal alternative to cannabis. In order to circumvent the German New Psychoactive Substances...
Synthetic cannabinoids become increasingly popular as a supposedly safe and legal alternative to cannabis. In order to circumvent the German New Psychoactive Substances Law, producers of so-called herbal mixtures rapidly design new substances with structural alterations that are not covered by the law. Acting as full agonists not only at the cannabinoid receptors 1 and 2, synthetic cannabinoids might have not only desired mental but also serious physical adverse effects. However, knowledge of adverse effects of specific substances is sparse and incomplete. This also accounts for 5F-Cumyl-PEGACLONE, a synthetic cannabinoid, which has been detected regularly in Germany in recent years. By using an animal model, the isolated perfused Langendorff heart, the study at hand aimed on finding out more about possible cardiovascular adverse effects of 5F-Cumyl-PEGACLONE. Hearts of male Wistar rats, which were excised postmortem, were exposed to two different concentrations of 5F-Cumyl-PEGACLONE: 13 hearts were exposed to 50 ng/ml and 12 hearts were exposed to 100 ng/ml. Thirteen control hearts were merely exposed to an additional amount of buffer solution. Functional parameters heart rate, minimal and maximum left ventricular pressure and coronary flow were documented at pre-defined time points during and after the administration of 5F-Cumyl-PEGACLONE/additional buffer solution. Electrocardiograms (ECGs) were documented throughout the experiments and evaluated afterwards. Kruskal-Wallis analysis was performed for each functional parameter as well as for the duration of the QRS complexes and the duration of RR intervals as derived from the ECGs. Furthermore, a multivariate analysis, comprising all functional and ECG parameters, was performed. Kruskal-Wallis analysis revealed only single significant p-values for QRS duration and minimum left ventricular pressure that did not pass a Bonferroni test. The results of the multivariate approach were also comparably homogeneous, but still the model correctly recognized hearts exposed to 100 ng/ml of 5F-Cumyl-PEGACLONE more often than hearts exposed to the low concentration of 5F-Cumyl-PEGACLONE or additional buffer solution. Evaluation of the ECGs presented single cases of ST depression and QT prolongation. Though certainly not unambiguous, these findings support the assumption that 5F-Cumyl-PEGACLONE can cause severe, if not lethal, cardiac adverse effects like arrhythmias or myocardial infarctions especially if it is consumed in combination with other drugs like alcohol or if the consumer suffers from pre-existing heart diseases.
Topics: Male; Rats; Animals; Rats, Wistar; Cannabinoids; Hallucinogens; Cannabis
PubMed: 38214738
DOI: 10.1007/s00414-023-03146-3