In July 1999, I took my final curtsey as an aspiring ballet dancer in London. At the time, I was devastated, having been ‘assessed out’ by the ballet school I’d attended the year after I finished high school in Ireland. I wish I knew then what I know now: there are no endings in a career, just different paths. It took a few more iterations for me to learn that lesson. I hope my experience can provide some reassurance for anyone out there grappling with their next career move.
Aims: To evaluate drug-drug interactions between carotegrast methyl, a CYP3A4 inhibitor, and other CYP3A4 substrates, midazolam, atorvastatin, and prednisolone. Methods: A total of 88 healthy volunteers orally received carotegrast methyl 960 mg three times daily for 14 days. A single oral (5 mg) or intravenous (0.017 mg kg-1) midazolam, oral (5 mg) prednisolone, or oral (10 mg) atorvastatin was administered before, with, and after carotegrast methyl treatment. When the 90% confidence interval (CI) for the geometric mean ratios of the pharmacokinetic (PK) parameters with coadministration with carotegrast methyl (day 14) to those before carotegrast methyl administration was between 0.80 and 1.25, no PK interaction were deemed. Results: The Cmax and AUC0-t of oral midazolam before administration of carotegrast methyl was 30.9 ± 9.8 ng mL-1 and 74.5 ± 21.9 ng h mL-1, respectively. The geometric mean ratio of the Cmax and AUC0-t of midazolam on day 14 to those on day -1 was 1.86 (90% CI, 1.64 – 2.11) and 3.07 (90% CI, 2.81 – 3.35), which did not fall within the range of 0.80 – 1.25, suggesting that carotegrast methyl had a PK interaction with midazolam. Similar PK interactions were found for intravenous midazolam and atorvastatin, but not for prednisolone. The inhibitory effect of carotegrast methyl on CYP3A4-mediated metabolism of midazolam and atorvastatin had almost disappeared by 14 days after the end of administration. Conclusion: Carotegrast methyl was classified as a moderate CYP3A4 inhibitor in humans. Carotegrast methyl might enhance the action of drugs that are metabolized by CYP3A4.
The objective of this study is to evaluate the effect of photobiomodulation (PBM) on pain control during pterygomandibular puncture. A patient received anesthesia on both sides of the mouth in a randomized manner. On the right side, an 808nm infrared low-level laser was applied before local anesthesia. On the left side, a sham laser was applied using the same technique. There was a 50% reduction in pain levels on the PBM-treated side compared to the sham PBM side, as measured by the visual analog scale. Sensitivity tests revealed that anesthesia was more effective on the PBM side. There was no significant difference in blood pressure before and after anesthesia on either side. While these findings are based on a single case report, they suggest that photobiomodulation before anesthesia may alleviate puncture pain associated with anesthesia. Nevertheless, further well-designed clinical trials are necessary to confirm the effectiveness of this complementary therapy.
The study of microbiomes across organisms and environments has become a prominent focus in molecular ecology. This perspective article explores methodological advancements, common challenges and future directions in the field. Key research areas include understanding the drivers of microbiome community assembly, linking microbiome composition to host genetics, exploring microbial functions, transience, and spatial partitioning, and disentangling non-bacterial components of the microbiome. Methodological advancements, such as quantifying absolute abundances, sequencing complete genomes, and utilizing novel statistical approaches, are also useful tools for understanding complex microbial diversity patterns. Our aims are to encourage robust practices in microbiome studies and inspire researchers to explore the next frontier of this rapidly changing field.
Title: Leadless Pacemakers in Post Operative Patients: Is It Time For the New to Become the Normal?Invited Editorial: Manuscript ID JCE-23-0567.R2Tyler P. Rasmussen, MD, PhD and E. Michael Powers, MD, MBAUniversity of Iowa Carver College of MedicineDivision of Cariology, Clinical Cardiac Electrophysiology200 Hawkins Dr.Iowa City, IA [email protected] et al. describe a single center retrospective analysis of leadless pacemaker (LP) implant following cardiac surgery or transcatheter valvular procedures that highlights the performance of LPs when implanted in patients with atrioventricular block (AVB) and either high risk features for conventional transvenous pacing or permanent atrial fibrillation (1). LPs performed well with a limited number of patients (7%) requiring conversion to transvenous pacing and only a single procedural complication. However, there was a statistically significant decline in left ventricular ejection fraction (LVEF) in the overall cohort. When subgroup analysis was performed, LVEF decline was only seen in those implanted with VVI devices but not in patients with VDD devices. Here, we discuss implications of this study.Transcatheter aortic valve implantation (TAVI) is now more common than surgical AVR but carries a greater risk of high degree atrioventricular block (AVB) (~10%) (2,3). Cardiac surgery has been linked to a 1-3% risk of permanent pacemaker implantation with higher rates in patients undergoing valve replacement (4). Therefore, the number of patients at risk for AVB related to cardiac surgery and catheter-based valve interventions is increasing over time and warrants a critical evaluation of optimal pacing strategy.Longitudinal registry data show that Micra (Medtronic, Minneapolis, MN) LPs have fewer required reinterventions and chronic complications compared to conventional transvenous pacing systems (5). Furthermore, mortality is comparable despite being implanted in patients with higher rates of end stage renal disease (ESRD) and medical complexity (5). LPs greatly outperform transvenous systems with respect to device related infections, as the rate of infection in LPs is trivial both short and long term (5,6). The risk of pacing induced cardiomyopathy (LVEF drop ≥ 10%) in pacemaker dependent patients is suggested to be equivalent or lower in those implanted with an LP (3%) versus those with a transvenous system (~13%) (7). A major drawback to the use of LPs is their inability to provide atrial pacing, which typically limits their use to patients without sinus node dysfunction.The current paper demonstrates that the use of LPs is a viable strategy in post-operative patients. Their cohort included 50 patients having undergone cardiac surgery and 28 with a transcatheter valvular procedure (1). Of the 28 transcatheter procedures, 25 were TAVI. Factors prompting an LP implant versus transvenous were permanent AF, ESRD, tricuspid valve pathology, history of endovascular infection, and dermatological disease. Mean time from surgery to device implant was 7.3 ± 8.0 days, which suggests an adequate waiting period for AV conduction recovery in most circumstances. The only complication in the cohort (1.3%) was an access site hematoma requiring evacuation. Device parameters were stable at follow-up with a small but clinically insignificant decline in impedance and trivial rise in threshold, which is consistent with previously published data regarding Micra (6). The two major findings were that the pacing burden declined significantly in the follow-up period and that there was a significant reduction in the left ventricular ejection fraction (LVEF) in this cohort. Pacing percentages fell from mean 75% at implant to mean 48% at follow-up. The reduction in pacing burden suggests that many patients have late recovery in AV conduction post procedure. There was a drop in LVEF from baseline (55.0% ± 10.6%) versus follow-up (51.5% ± 11.2%, p =< 0.001), but this study is not designed to determine if the LVEF drop is because of the Micra or another unidentifiable factor. Importantly, the drop in LVEF was significant in the Micra VR group: baseline (54.1% ± 11.9%) versus follow-up (48.8% ± 11.9%, p = 0.003) but not in the Micra AV group: baseline (56.1 ± 9.0%) versus (54.6% ± 9.7%, p = 0.06). The only patient characteristic that was associated with a significant drop in LVEF (> 10%) versus those with stable EF was having a prior history of heart failure with a reduced ejection fraction. Taken together, this study showed that both Micra AV and VR can provide safe RV pacing in post-operative patients with a small, but significant risk for LVEF reduction that is likely linked to right ventricular pacing.
INTRODUCTIONThe concept of cantilevered fixed partial denture (CFPD) was described as early as 1960.1 Subsequently, the innovations in dental materials and adhesive dentistry allowed for the description of full ceramic CFPDs as a sound solution for the replacement of missing anterior teeth in 1997.2 Since this initial description, this therapeutic solution has provided patients with a minimally invasive alternative to three-unit fixed partial dentures (FPD). The indication of CFPD is often disputed in comparison with an implant-based treatment, which in some cases, can present challenges, or even be contraindicated. In this regard, CFPDs benefits from more reproducible esthetics, quicker execution and lower costs.2The question remains, however, whether this method would also be suitable for the replacement of missing teeth in the posterior sector, the main problem being the significant increase in occlusal loads on the premolars and molars.3 Different teams have begun to develop posterior CFPDs and some already have the necessary follow-up to validate this practice.4-8 The material used in these early clinical trials has been zirconia doped with 3%mol yttrium oxide (3Y-TZP), which gives the best mechanical properties at the expense of low aesthetic translucency. Yazigii and Kern recommend a thickness of 0.7mm zirconia of the overlay part and a connector of at least 3mm in vertical section and 3mm in horizontal section to ensure the mechanical resistance of the CFPD’s pontic in the posterior sector.6 This case report describes the realization of a reinforced glass-ceramic CFPD replacing à first premolar, this material opens the possibility of single appointment chairside production, and has superior adhesive and esthetic characteristics compared to zirconia.9-11 Its lower mechanical resistance is however to be taken into consideration,12 but still might be suitable if some prerequisites are met.
Heterogeneous catalysts promoting efficient production of reactive species and dynamically stabilized electron transfer mechanisms for peroxomonosulfates (PMS) still lack systematic investigation. Herein, a more stable magnetic layered double oxides (CFLDO/N-C), was designed using self-polymerization and high temperature carbonization of dopamine. The CFLDO/N-C/PMS system effectively activated PMS to remove 99% (k=0.737 min-1) of tetracycline (TC) within 10 min. The CFLDO/N-C/PMS system exhibited favorable resistance to inorganic anions and natural organics, as well as satisfactory suitability for multiple pollutants. The magnetic properties of the catalyst facilitated the separation of catalysts from the liquid phase, resulting in excellent reproducibility and effectively reducing the leaching of metal ions. An electronic bridge was constructed between cobalt (the active platform of the catalyst) and PMS, inducing PMS to break the O-O bond to generate the active species. The combination of static analysis and dynamic evolution confirmed the effective adsorption of PMS on the catalyst surface as well as the strong radical-assisted electron transfer process. Eventually, we further identified the sites where the reactive species attacked the TC and evaluated the toxicity of the intermediates. These findings offer innovative insights into the rapid degradation of pollutants achieved by transition metals in SR-AOPs and its mechanistic elaboration.
The side-chain has a significant effect on the optical properties and aggregation behaviors of the organic small molecule acceptors, which becomes an important strategy to optimize the photovoltaic performance of organic solar cells (OSCs). In this work, we designed and synthesized three novel nonfused ring electron acceptors (NFREAs) OC4-4Cl-Ph, OC4-4Cl-Th and OC4-4Cl-C8 with hexylbenzene, hexylthiophene and octyl side chains on the π-bridge units. Compared with OC4-4Cl-Ph and OC4-4Cl-Th, OC4-4Cl-C8 with linear alkyl side chain has more red-shift absorption, which is conducive to obtaining higher short-circuit current density. Additionally, the OC4-4Cl-C8 film exhibits a longer exciton diffusion distance and the D18:OC4-4Cl-C8 blend film displays faster hole transfer, weaker bimolecular recombination, and more efficient exciton transport. Furthermore, the D18:OC4-4Cl-C8 blend films can form good nano fibril-like interpenetrating networks, which can facilitate exciton dissociation and charge transport. Finally, OC4-4Cl-C8 based devices can generate an excellent PCE of 16.56%, which is much higher than OC4-4Cl-Ph (12.29%) and OC4-4Cl-Th based (11.00%) ones, being the highest PCE among the NFREA based binary devices. All in all, we have demonstrated that side-chain engineering is an efficient way to achieve high-performance NFREAs.
Amyloid-β peptide (Aβ) oligomers, characteristic symptom of Alzheimer’s disease (AD), have been identified as the most neurotoxic species and significant contributors to neurodegeneration in AD. However, due to their transient and heterogeneous nature, the high-resolution structures and exact pathogenic processes of Aβ oligomers are currently unknown. Using light-controlled molecular tweezers (LMTs), we describe a method for precisely capturing specific Aβ oligomers produced from synthetic Aβ and AD animal models. Light irradiation can activate LMTs, which are composed of two Aβ-targeting pentapeptides (KLVFF) motifs and a rigid azobenzene (azo) derivative, to form a tweezer-like cis configuration that preferentially binds to specifc oligomers matching the space of the tweezers via multivalent interactions of KLVFF motifs with the oligomers. Surprisingly, cis-LMTs can immobilize the captured oligomers in transgenic Caenorhabditis elegans (C. elegans) in vivo under light irradiation. The LMTs may serve as spatiotemporally controllable molecular tools to extract specific native oligomers for the structure and function studies via their reversible photoisomerization, which would improve the understanding of the toxic mechanisms of Aβ oligomers and development of oligomer-targeted diagnosis and therapy.
Fluorescent-magneto nanoemitters have gained considerable attention for their applications in mechanical controlling-assisted optical signaling. However, the incompatibility between magnetic and fluorescent components often leads to functional limitations in traditional magneto@fluorescence nanostructure. Herein, we introduce a new compact-discrete spatial arrangement on a “fluorescence@magneto” core–shell nanostructure consisting of a close-packed aggregation-induced emission luminogen (AIEgen) core and a discrete magnetic shell. This structural design effectively eliminates the optical and magnetic interferences between the dual components by facilitating AIEgens loading in core region and reducing the magnetic feeding amount through effective exposure of the magnetic units. Thereby, the resulting magneto-AIEgen nanoparticle (MANP) demonstrates “win-win” performances: (i) high fluorescent intensity contributed by AIEgens stacking-enhanced photoluminescence and reduced photons loss from the meager magnetic shell; (ii) marked magnetic activity due to magneto extraposition-minimized magnetic shielding. Accordingly, the dual functions-retained MANP provides a proof of concept for construction of an immunochromatographic sensing platform, where it enables bright fluorescent labeling after magnetically enriching and separating procalcitonin and lipoarabinomannan in clinical human serum and urine, respectively, for the clinical diagnosis of bacterial infections-caused inflammation and tuberculosis. This study not only inspires the rational design of magnetic-fluorescent nanoemitter, but also highlights promising potential in magneto-assisted point-of-care test and biomedicine applications.
Spontaneous Spinal Cord Herniation with Post-operative paraplegia- A case report with 10-year follow-upAbstract:Background: Spinal cord herniation is an uncommon diagnosis in the field of spine surgery. The usual presentation of spontaneous spinal cord herniation is in the form of progressive Brown-Sequard syndrome. We describe a case of a 37-year-old male with progressive back pain and sensory deficits due to spinal cord herniation and a post-operative complication associated with reduction of the hernia.Case description: A 37-year-old male presented with insidious onset upper back pain and altered sensations of pain and temperature over the right half of the body below the nipple 2 months before the examination. The patient did not have motor weakness of lower limbs, abnormal/ involuntary movements, or loss of control over the bowel and bladder. MRI of the thoracic spine showed an anterolateral defect(left) at the level of the T2-T3 vertebra. A posterior approach was chosen and the cord with roots was reduced into the dura. The defect was covered by a dural graft (Lyodura) and the wound was closed with a drain insitu. On the 3rd post-operative day, patient developed paraplegia. Patient was treated by exploration and decompression of the hematoma that compressed spinal cord. The deficits were completely recovered at one-month follow-up.Conclusion: Patients with spinal cord herniation and neurologic deficits when treated timely with reduction of the hernia, have good outcomes. The drain should be removed only when the treating team is satisfied regarding the lack of ongoing hemorrhage. The recovery was maintained till the last follow-up at 10 years.Key words: spontaneous spinal cord herniation, spinal cord defect, paraplegia, Brown-Sequard syndrome
INTRODUCTIONAn unpleasant experience for both the patient and the anesthetist, post-dural puncture headache (PDPH) is a complication of spinal anesthesia or lumbar puncture. It is believed to be caused by cerebral vasodilation, which is an indirect consequence of low cerebrospinal fluid (CSF) pressure, or meningeal traction linked to low CSF pressure.1 PDPH incidence varies, although it is generally thought to be 36% or more after lumbar puncture, 0%-10% after spinal anesthesia, and 81% after an unintentional dural puncture during epidural insertion.2, 3 Although PDPH typically resolves on its own, it can make it difficult for mothers to care for their infants and lengthen hospital stays. Serious side effects such as subdural hematoma, convulsions, sagittal sinus thrombosis, and cranial nerve palsies are more infrequently linked to PDPH.
Background and Objectives: Initially developed as immunosuppressive agents, mTOR inhibitors are currently used widely in the management of vascular malformations and tumors. The incidence of infectious complications in the vascular anomalies (VA) population is not well defined. The goal of this systematic review was to better define the types and severity of reported infectious complications in patients with VAs treated with mTOR inhibition. Methods: This was a systematic review conducted following PRISMA guidelines evaluating all research articles focused on infectious complications in patients with VAs treated with sirolimus or everolimus. Thirty articles including 1181 total patients and 315 infections (in 290 unique patients) were ultimately included. Results: The majority of infections were viral upper respiratory (n=137, 54%), followed by pneumonia (n=52, 20%), and cutaneous infections (n=20, 8%). There were 6 total infection-related fatalities, which all occurred in patients younger than 2 years. Only 1 case of Pneumocystis jirovecii pneumonia (PJP) was reported. This was in an infant with KHE who was also treated with steroids and did not receive PJP prophylaxis. Almost 1/3 (n=95, 32%) of infectious complications were graded 3 to 4 according to CTCAE criteria. Details of patient age, subtype of VA, and timing of infection were lacking from many reports. Conclusions: Most infectious complications reported in patients with VA on mTOR inhibitors were viral respiratory infections and non-severe. Bacteremia, infectious fatalities, and PJP are exceedingly rare. Future studies are needed to clarify the spectrum of infectious risks in VA patients and to provide guidance for infection prevention.
While the survival of children with cancer has improved over time, infection remains a major morbidity and mortality risk. We conducted a systematic literature review to determine the unmet needs in diagnosing infection in immunocompromised children with cancer. The comprehensive search strategy followed the guidelines established by the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement and spanned multiple bibliographic databases and other public sources from January 1, 2012–June 23, 2022. From 5,188 records, 34 unique pediatric-focused studies met inclusion criteria. This review highlights the lack of published data on infectious disease testing in pediatric oncology patients and the need for well-designed clinical impact and cost-effectiveness studies of both existing and novel diagnostic platforms. Such studies are necessary to optimize diagnostic and antimicrobial stewardship, leading to improvement in patient outcomes.
α-Olefins as aliphatic terminal alkenes could be obtained easily from numerous contemporary synthetic reactions as well as petrochemical industry, and also found in natural products. Compared to the alkenes attaching the directing groups or activating group, the catalytic asymmetric reaction of unactivated terminal alkenes presents great challenges due to the weak electron effect and small steric hindrance effect. This review mainly summerizes the latest progress of the asymmetric reaction of unactivated terminal olefins since 2016.
Scientific outreach activities play an important role in disseminating knowledge, connecting the general public to research and breaking down scientific scepticism barriers. However, the vision impaired community is often disadvantaged when the most common audio-visual approach of scientific communication is applied. Here we integrated tactile clues in the scientific communication of immune processes involved in the autoimmune skin disease psoriasis. We encouraged participation of the vision impaired community by engagement with tactile scientific origami art, a haptic poster and wood carved molecular models. Readily accessible science communication that engages a number of senses is a critical step towards making science more inclusive, and engaging for individuals with a wide range of sensory abilities. The Sensory Science approach aligns with the principles of equity, diversity, and inclusion and helps create a more informed and scientifically literate public.