Objectives
Determine the true incidence and time course of atrial fibrillation (AF) after patent foramen ovale closure (PFOc) using implantable loop recorders (ILR) placed during cryptogenic stroke ...evaluation.
Background
Published trials report a 2%–6.6% incidence of postimplant atrial fibrillation (PIAF) after PFOc, which is probably a gross underestimation, as only patients presenting in AF were captured. Episodes of paroxysmal and silent AF would have been missed.
Methods
Of 761 patients who underwent PFOc at a single center between January 2016 and December 2020, 35 patients had an ILR implanted before PFOc, without documentation of AF, and had ≥1 month of monitoring post‐PFOc. The incidence, onset, and conclusion of AF episodes were determined from a review of patient records.
Results
The mean duration of ILR monitoring was 54.6 ± 39.4 weeks after PFOc. AF occurred in 13/35 (37%) patients. PFOc patients who developed PIAF were older than those who did not (62 ± 11 vs. 52 ± 14 years, p = 0.03). In 12/13, the initial PIAF event occurred within 4 weeks of PFOc, with the greatest frequency around 2 weeks and conclusion by 12 weeks in all. No recurrent strokes occurred during ILR monitoring.
Conclusion
The actual incidence of PIAF was far greater than previously reported and was significantly associated with older age at PFOc. The timing of PIAF onset and termination were consistent with a postimplant inflammatory mechanism. The higher actual PIAF incidence underscores its low stroke potential in this population. A larger prospective trial is required to validate these preliminary results.
Schematic diagram of a glucose-responsive nanodrug delivery system. (a) Schematic diagram of the synthesis of VB12-FU-ConA@Ins nanocarriers. (b) Mechanism of Insulin release by VB12-FU-ConA ...stimulated by glucose.
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The smart oral administration Insulin device has the potential to improve glycemic management. It can reduce the risk of hypoglycemia associated with exogenous Insulin (INS) therapy while also avoiding many of the disadvantages associated with subcutaneous injections. Furthermore, diabetes mellitus (DM) is an endocrine illness characterized by inflammation, and it is critical to minimize the amount of inflammatory markers in diabetic patients while maintaining average blood glucose. In this study, a responsive nanosystem vitamin B12-Fucoidan-Concanavalin A (VB12-FU-ConA NPs) with anti-inflammatory action was developed for smart oral delivery of Insulin. Con A has high sensitivity and strong specificity as a glucose-responsive material. Fucoidan has anti-inflammatory, immunomodulatory, and hypoglycemic functions, and it can bind to Con A to form a reversible complex. Under high glucose conditions, free glucose competitively binds to Con A, which swells the nanocarrier and promotes Insulin release. Furthermore, in the low pH environment of the gastrointestinal tract, positively charged VB12 and anionic fucoidan bind tightly to protect the Insulin wrapped in the carrier, and VB12 can also bind to intestinal epithelial factors to improve transit rate, thereby promoting INS absorption. In vitro tests showed that the release of nanoparticles in hyperglycemic solutions was significantly higher than the drug release in normoglycemic conditions. Oral delivery of the nanosystems dramatically lowered blood glucose levels in type I diabetic mice (T1DM) during in vivo pharmacodynamics, minimizing the risk of hypoglycemia. Blood glucose levels reached a minimum of 8.1 ± 0.4 mmol/L after 8 h. Administering the nanosystem orally notably decreased the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in diabetic mice. The nano delivery system can be degraded and metabolized in the intestinal tract after being taken orally, demonstrating good biodegradability and biosafety. In conclusion, the present study showed that VB12-FU-ConA nanocarriers are expected to be a novel system for rationalizing blood glucose.
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•A south-to-north sampling profile of thermal springs in Sangri-Cona rift (SCR)•Magmatic fluid inputs are identified in geothermal systems of the central SCR.•Geochemical evidence for ...magmatic fluids agrees with magnetotelluric results.•Geothermal systems are related to orogenic extension and upwelling of crustal melts.
Fault-controlled geothermal systems in the Himalayan-Tibetan orogen could receive heat and material from deep-seated magmas due to crustal anatexis in orogenic settings. The near N-S trending rifts in southern Tibetan Plateau host abundant geothermal systems but potential role of residual magmas remains less constrained. Here, we evaluate magmatic contributions to geothermal systems in Sangri-Cona rift (SCR), the youngest rift in southern Tibetan Plateau, based on chemical and isotopic compositions of thermal waters from a south-to-north sampling profile. Our results show that the thermal springs in the central SCR have significant inputs from magmatic fluids, which account for high B concentrations and positive shift in δ18OH2O, while those in the southern and northern SCR are dominated by recharge of meteoric water. Water-rock interaction constrained by 87Sr/86Sr, hydrochemistry, and geothermometry results, suggests a hotter or deeper groundwater circulation path beneath central SCR than that of the southern and northern SCR. The identified magmatic fluid inputs, higher reservoir temperature, and higher degrees of water–rock interaction in the central SCR agree well with the presence of high conductivity anomalies at crustal depths of ∼ 10–30 km revealed by magnetotelluric surveys. Our findings provide geochemical evidence for the impact of lithospheric extension and associated geological and geophysical expressions (e.g., extension-induced exhumation of genesis domes that recorded crustal anatexis and upwelling of partially molten crustal channel flows) on modern geothermal systems in collisional orogens.
•Cona rift is the easternmost rift in the Himalayas.•Multi-thermochronometers suggest 3.0–2.3 Ma rift initiation.•Initiation of Himalayan rifts youngs monotonically eastward.•Lithospheric flow driven ...by asynchronous GPE gradients caused E–W extension.
Several competing hypotheses have been proposed to explain east-west extension observed across the Himalayan orogen, based primarily on observations from the western and central Himalaya. They make predictions for the temporal and spatial patterns of deformation in the eastern Himalaya. These tectonic models include radial spreading or oroclinal bending of the Himalayan arc, oblique convergence of the Indian continent, tearing or lateral detachment of the Indian slab and eastward flow of lithosphere. Here, for the first time we constrain the activity history of the Cona rift, the only north-trending rift currently recognized in the eastern Himalaya, based on biotite and K-feldspar 40Ar/39Ar and zircon and apatite (U–Th)/He thermochronology, to evaluate these proposed rifting mechanisms. Low-temperature thermochronological results suggest that the Cona rift is the youngest rift system in the Himalayas: after a slow phase of exhumation since ∼14 Ma (∼0.2–0.13 mm/yr), normal faulting initiated here at ∼3.0–2.3 Ma with a fault slip rate of ∼3.8–1.6 mm/yr and a horizontal extension magnitude of ∼2–5 km. Analysis of rifting across the Himalayas shows that rift initiation ages young eastward, which is matched by eastward decreasing rift-extension magnitudes. Monotonically eastward younging rift development is consistent with the tectonic model involving eastward lithospheric flow driven by Indian slab dynamics and coupled asynchronous gravitational potential energy gradients.
•A culture-free, enzyme-free, secondary antibody-free, and ultra-sensitive biosensor was established for Salmonella detection.•The Fenton reaction of Ni-TCPP(Fe2+) significantly improved the SNR of ...the biosensor (SNR›20).•The ConA not only improves the stability but also enhances sensitivity of the biosensor.•The strategy was successfully applied for the detection of Salmonella from human urine.
To fulfill the stringent demands of clinical Salmonella detection, this study employed the benefits of Ni-TCPP(Fe2+) and ConA to establish a novel approach that is culture-free, enzyme-free, secondary antibody-free, and ultra-sensitive. Our investigations revealed two key mechanisms that significantly bolster the signal-to-noise ratio (SNR) and enhance detection stability: firstly, the Fenton reaction and the mimic enzyme catalysis of Ni-TCPP(Fe2+) improved the sensitivity of the biosensor; secondly, the substitution of the secondary antibody with ConA led to increased binding of Ni-TCPP(Fe2+) due to the abundance of ConA receptors on the bacterial surface. With proper assembly, the developed biosensor exhibited high sensitivity in the range of 101–107 CFU/mL, along with a detection limit as low as 4 CFU/mL, and achieved rapid detection within a mere 2 h. Moreover, this biosensor has proven its efficacy in detecting Salmonella in clinical biological samples. Its advantages of being culture-free, secondary antibody-free, and ultra-sensitive establish a solid research foundation for the expedited detection of Salmonella in clinical settings and point-of-care testing (POCT).
Objectives
To assess the short‐ and long‐term outcomes of balloon pulmonary valvuloplasty (BPV) in children with Noonan syndrome (NS).
Background
Pulmonary stenosis (PS) is the most common congenital ...heart lesion in NS. BPV is the accepted first line treatment in PS. However, BPV in NS patients has been reported to be less effective, without specific factors for the need for reintervention being identified.
Methods
Retrospective case‐note review of all patients with NS who underwent BPV between 1985 and 2020. Patients were divided into 2 groups: those with supravalvular pulmonary stenosis (SPS) in addition to valvar PS, and those with isolated valvar PS.
Results
A cohort of 54 patients with NS underwent BPV at a median of 275 (interquartile range IQR: 108–575) days of age. SPS was present in 32 (59%) patients whereas 22 had (41) isolated PS. The preprocedural invasive gradient was 47 (IQR: 35–69) mmHg, and 44 (IQR: 35–48) mmHg in those with SPS and those without respectively (p = 0.88). Reintervention was required in 22 patients (41%): 17 (77%) with SPS and 5 (23%) without (p = 0.017). Fourteen patients (11 with SPS) required surgical reintervention and 8 (6 with SPS) required further BPV. There was no significant difference in the age at initial BPV, pre‐ and postprocedural gradients and interval until reintervention between groups.
Conclusion
This is the largest reported cohort of patients with NS undergoing BPV. Although BPV is often successful, the reintervention rates are high. SPS was a risk factor for reintervention.
A green synthesis of functionalized 4H‐chromenes using one‐pot, three‐component reaction of salicylaldehyde (1), active methylene (2), and carbon‐based nucleophile (3) using Fe3O4@CONa nanoparticles ...in water has been performed at 60°C. The Fe3O4@CONa nanoparticle as an efficient, green, and magnetically reusable heterogeneous catalyst was applied in these reactions up to the nine runs. Green catalyst and solvent, short reaction time, high product yields, as well as simple work‐up procedure were found as some advantages of this methodology. The density functional theory calculations were applied to all‐inclusive perception of the one‐pot, three‐component reaction mechanism. The most reactions progressed through the following route: (a) nucleophilic addition of 2 to 1; (b) ring closing, dehydration; (c) nucleophilic substitution of 3 (2‐naphtol, 4‐hydroxycumarin) to intermediate. Sometimes mechanism mutated to: (a) nucleophilic addition of 3 (indole, 2‐methylindole) to 1, and dehydration; (b) nucleophilic addition of 2 to intermediate; and (c) ring closing, and dehydration. The frontier molecular orbitals, NBO analyses, molecular electrostatic potential of reactants, and intermediates confirmed the proposal mechanisms. Theoretical study could be so helpful to pick out suitable reactants of the reaction.
Density functional theory (DFT) calculations were applied to study of the one‐pot, three‐component synthesis of functionalized 4H‐chromenes in basic medium.
DFT study identified two various mechanisms due to different reactants.
The frontier molecular orbitals, NBO analyses, molecular electrostatic potential of reactants, and intermediates confirmed the proposal mechanisms.
Theoretical study helped to choose suitable reactants of salicylaldehyde (1), active methylene (2), and carbon‐based nucleophile (3).
The Fe3O4@CONa nanoparticle was synthesized and applied as an efficient, green, and magnetically reusable heterogeneous catalyst in the reaction.
Green synthesis of functionalized 4H‐chromenes performed using Fe3O4@CONa nanoparticles in water at 60°C.
Objectives
Lipoarabinomannan (LAM), an abundant cell wall glycolipid of mycobacteria including
Mycobacterium tuberculosis
(
Mtb
), is a promising TB diagnostic marker. The current commercially ...available urine LAM assays are not sufficiently sensitive, and more novel detection strategies are urgently needed to fill the current diagnostic gap.
Methods
A proteinase K-pretreated Concanavalin A (ConA)-based ELISA assay was developed. Diagnostic performance was assessed by several bacterial strains and clinical urine samples.
Results
The limit of detection (LoD) of the assay against ManLAM was 6 ng/ml. The assay reacted strongly to
Mtb
H37Rv and
M. bovis
BCG, intermediately to
M. smegmatis
mc
2
155, and weakly to four non-mycobacteria pathogens. This method could distinguish TB patients from healthy controls (HCs) and close contacts (CCs) in 71 urine samples treated with proteinase K, which increases urine LAM antibody reactiveness. In TB
+
HIV
+
and TB
+
HIV
−
patients, the sensitivity was 43.8 and 37.5%, respectively, while the specificity was 100.0%. The areas under ROC curves (AUCs) were 0.74 and 0.82, respectively.
Conclusion
This study implies that ConA can be paired with antibodies to detect LAM. Proteinase K treatment could effectively enhance the sensitivity by restoring the reactiveness of antibodies to LAM.
The intravenous injection of the plant lectin concanavalin A (ConA) is a widely used model for acute immune-mediated hepatitis in mice. In contrast to several other models for acute hepatic damage, ...ConA-induced injury is primarily driven by the activation and recruitment of T cells to the liver. Hence, the ConA model has unique features with respect to its pathogenesis and important similarities to immune-mediated hepatitis in humans, such as autoimmune hepatitis, acute viral hepatitis or distinct entities of drug toxicity leading to immune activation. However, the ConA model has considerable variability, depending on the preparation of the compound, genetic background of the mice, sex, age and microbial environment of the animal facility barrier. This standard operating procedure (SOP) comprises a detailed protocol for the ConA application, including preparation of ConA working solution, handling of the animals, choice of the appropriate conditions and endpoints, as well as efficient dose-finding.
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