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Background and Aims: During endoscopic sinus surgery, anaesthetic conditions significantly impact the intraoperative surgical field and bleeding during emergence. While the endotracheal tube (ETT) has been traditionally used in sinus surgery, a reinforced laryngeal mask airway (RLMA) that produces less upper airway stimulation may result in smoother emergence., Methods: A randomised controlled trial of 72 patients undergoing elective sinus surgery was conducted, with the allocation of airway technique to either ETT with a throat pack or RLMA. The primary outcome measure was emergence time, measured by time to opening eyes on commands at the cessation of anaesthesia, and the secondary outcomes were time to removal of airway device, remifentanil use, procedure times, mean arterial pressure (MAP) and the RLMA grade of blood contamination. The continuous variables were analysed using Student's t -tests and discrete variables, count tables were analysed using Fisher's exact tests., Results: There was no significant difference in the emergence time between the ETT and RLMA groups ( P = 0.83). Remifentanil use was significantly higher in the ETT group than in the RLMA group ( P = 0.022). The ETT group showed a significantly increased total anaesthetic time ( P = 0.01). MAP was not significant during preinduction, maintenance or post-RMLA removal. The highest grade of contamination was grade 2 in RLMA. RLMA had lower rates of postoperative adverse events., Conclusions: RLMA comparable to ETT in terms of emergence time. The RMLA group had lower remifentanil use, anaesthesia duration and fewer postoperative adverse events such as cough and throat pain., Competing Interests: Professor Alkis J Psaltis is a consultant for Medtronic and Neurent and is on the speakers bureau for GlaxoSmithKline, Sanofi, Karl Storz and Sequiris. He is a shareholder in Chitogel., (Copyright: © 2024 Indian Journal of Anaesthesia.)

Cellular functions crucially depend on the precise execution of complex biochemical reactions taking place on the chromatin fiber in the tightly packed environment of the cell nucleus. Despite the availability of large datasets probing this process from multiple angles, bottom-up frameworks that allow the incorporation of the sequence-specific nature of biochemistry in a unified model of 3D chromatin structure remain scarce. Here, we propose Sequence-Enhanced Magnetic Polymer (SEMPER), a novel stochastic polymer model that naturally incorporates observational data about sequence-driven biochemical processes, such as binding of transcription factor proteins, in a 3D model of chromatin structure. We introduce a novel approximate Bayesian algorithm to quantify a posteriori the relative importance of various factors, including the polymeric nature of DNA, in determining chromatin epigenetic state, thus providing a transparent way to generate biological hypotheses. Although accurate prediction of contact frequencies (a problem already extensively studied in the literature) is not our main aim, as a by-product of the inference procedure and without additional input from the genome 3D structure, our model can predict with reasonable accuracy some notable and nontrivial conformational features of chromatin folding within the nucleus. Our work highlights the importance of introducing physically realistic statistical models for predicting chromatin states from epigenetic data and opens the way to a new class of more systematic approaches to interpreting epigenomic data., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Cellular longevity is regulated by both genetic and environmental factors. However, the interactions of these factors in the context of aging remain largely unclear. Here, we formulate a mathematical model for dynamic glucose modulation of a core gene circuit in yeast aging, which not only guided the design of pro-longevity interventions, but also revealed the theoretical principles underlying these interventions. We introduce the dynamical systems theory to capture two general means for promoting longevity - the creation of a stable fixed point in the "healthy" state of the cell and the dynamic stabilization of the system around this healthy state through environmental oscillations. Guided by the model, we investigate how both of these can be experimentally realized by dynamically modulating environmental glucose levels. The results establish a paradigm for theoretically analyzing the trajectories and perturbations of aging that can be generalized to aging processes in diverse cell types and organisms., Competing Interests: Declaration of Interests The authors declare no competing interests.

This article reviews current medical literature to assess the benefits and drawbacks of virtual interviews for radiology residencies as well as the downstream effects of these changes, best practices, and potential future recruitment methods. Topics covered include the effects of remote recruitment in promoting accessibility and applicant diversity and equality as well as fiscal, environmental, and time savings in combination with technical challenges, the complications of over application, challenges in assessment of program culture and location, impact on morale, and hidden financial and emotional costs. Learnings from other medical specialties are highlighted in addition to the process of signaling, guidelines for conducting and participating in virtual interviews, and matters for future consideration., (Copyright © 2022 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the hospital- and patient-related factors associated with increased likelihood of inpatient admission and extended hospitalization., Methods: We applied multivariate logistic regression to a subset of ED hospital and patient characteristics linearly extrapolated from the 2019 National Emergency Department Sample database (n=626,508). Patient characteristics with 10 or fewer ED visits after national extrapolation were not reported in the current study to maintain patient confidentiality, in accordance with the HCUP Data Use Agreement. All selected ED visits represented a primary diagnosis of CVD (ICD-10 codes 160-168). All reported hospital and patient characteristics were subject to adjustment for covariates. P-values < 0.05 were considered statistically significant., Main Findings: Medicare beneficiaries report higher inpatient admission rates than uninsured OR 0.81 (0.73-0.91) and privately insured OR 0.86 (0.79-0.94) individuals. Black and Native-American patients were 37% and 55% more likely to be hospitalized long (>75 th percentile) (OR 1.37 [1.25-1.50], OR 1.55 [1.14-2.10]). Northeast emergency departments reported an increased odds of admission compared to the Midwest OR (0.40-0.62), South OR 0.79 (0.63-0.98) and West OR 0.52 (0.39-0.69). Patients with multiple comorbidities (mCCI = 3+) were 226% more likely to have a longer stay OR 3.26 (3.09-3.45) than patients presenting with zero or few comorbidities. Level I, II, and III trauma centers report distinctly high odds of inpatient admission (OR 3.54 [2.84-4.42], OR 2.68 [2.14-3.35], OR 1.51 [1.25-1.84])., Principal Conclusions: Likelihoods of inpatient admission and long hospital stays were observably stratified through multiple, independently acting hospital and patient characteristics. Significant associations were stratified by race/ethnicity, location, and clinical presentation, among others. Attention to the factors reported here may serve well to mitigate emergency department crowding and its sobering impact on United States healthcare systems and patients., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest, (Copyright © 2023 Elsevier Inc. All rights reserved.)

The tumor-associated antigen mesothelin is expressed at high levels on the cell surface of many human cancers, while its expression in normal tissues is limited. The binding of mesothelin to the tumor-associated cancer antigen 125 (CA-125) can lead to heterotypic cell adhesion and tumor metastasis within the pleural and peritoneal cavities. Immunotherapeutic strategies targeting mesothelin are being intensively investigated. Here, we report the crystal structures of mesothelin that reveal a compact, right-handed solenoid consisting of 24 short helices and connecting loops. These helices form a nine-layered spiral coil that resembles ARM/HEAT family proteins. Glycan attachments have been identified in the structure for all three predicted N-glycosylation sites and confirmed with samples from cell culture and patient ascites. The structures of full-length mesothelin and its complex with the Fab of MORAb-009 reveal the interaction of the antibody with the complete epitope, which has not been reported previously. The N-terminal half of mesothelin is conformationally rigid, suitable for eliciting specific antibodies, whereas its C-terminal portion is more flexible. The structure of the C-terminal shedding-resistant fragment of mesothelin complexed with a mAb 15B6 displays an extended linear epitope and helps explain the protection afforded by the antibody for the shedding sites., Significance: The structures of full-length mesothelin and its complexes with antibodies reported here are the first to be determined experimentally, providing atomic models for structural organization of this protein and its interactions with antibodies. It offers insights into the function of mesothelin and guidance for further development of therapeutic antibodies., Competing Interests: I. Pastan reports a patent to WO 2014031476 pending. No disclosures were reported by the other authors., (© 2023 The Authors; Published by the American Association for Cancer Research.)

In carpal tunnel syndrome (CTS), the median nerve is compressed at the level of the carpal tunnel in the wrist. This entrapment manifests as unpleasant symptoms, such as burning, tingling, or numbness in the palm that extends to the fingers. As the disease progresses, afflicted individuals also report decreased grip strength accompanied by hand weakness and restricted movement. The first half of this review elaborates on CTS pathology by providing readers with a comprehensive understanding of the etiology, relevant anatomy, and disease mechanism. CTS is considered the most common entrapment neuropathy, affecting around 3-6% of the adult population. Further, CTS prevalence has seen a dramatic increase in the last few decades paralleling the growth of everyday technology usage. Despite how common it is to have CTS, it can be quite challenging for physicians to make a definite diagnosis due to differentials that present with overlapping symptoms. Even more difficult can be deciding on a course of treatment that is the most effective and considerate of patient needs. Thus arises the need for clear clinical direction, and hence we end with a discussion around such guidelines that serve as a starting point toward effective diagnoses and patient treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Joshi et al.)

Non-invasive measurement of the arterial blood speed gives important health information such as cardio output and blood supplies to vital organs. The magnitude and change in arterial blood speed are key indicators of the health conditions and development and progression of diseases. We demonstrated a simple technique to directly measure the blood flow speed in main arteries based on the diffused light model. The concept is demonstrated with a phantom that uses intralipid hydrogel to model the biological tissue and an embedded glass tube with flowing human blood to model the blood vessel. The correlation function of the measured photocurrent was used to find the electrical field correlation function via the Siegert relation. We have shown that the characteristic decorrelation rate (i.e., the inverse of the decoherent time) is linearly proportional to the blood speed and independent of the tube diameter. This striking property can be explained by an approximate analytic solution for the diffused light equation in the regime where the convective flow is the dominating factor for decorrelation. As a result, we have demonstrated a non-invasive method of measuring arterial blood speed without any prior knowledge or assumption about the geometric or mechanic properties of the blood vessels.

Human immunodeficiency virus (HIV) is a viral infection that, when transmitted through the exchange of certain bodily fluids, destroys various immune cells and contributes to an overall weakened immune system. If left untreated, HIV progresses to acquired immunodeficiency syndrome (AIDS) - a chronic, life-threatening condition that puts patients at risk for opportunistic infections. Since the emergence of HIV nearly a century ago, the world has seen tremendous advances in elucidating its pathology and progression. These advances have been accompanied by an increased understanding of how subsequent effects and symptoms manifest in afflicted individuals. These discoveries, coupled with the ever-improving technologies and methodologies used for detection and treatment, provide the scientific and medical community with a solid grasp of HIV. Despite this significant headway, there is still much progress to be made; medical advances have allowed people with HIV to manage their disease and live a longer, healthier life, but a definite cure is yet to be found. Thus, the following literature review serves as both an extensive compendium of our current understanding of HIV - its pathology, testing/detection, repercussions, and treatment - and an acknowledgement of the areas that still require further research., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Patel et al.)

Zebrafish are being increasingly used as animal models for human diseases such as cardiomyopathy and neuroblastoma. Owing to a nearly fully sequenced genome and efficient genetics/chemical genetics, zebrafish open new research opportunities for human diseases research. The purpose of this study was to develop zebrafish ultrasound vibro-elastography (ZUVE) for measuring the shear wave speed of zebrafish. An adult female zebrafish was anesthetized for three minutes for the ZUVE testing. A 0.1 s gentle harmonic vibration was generated on the tail using a sphere tip indenter with 3 mm diameter. Shear wave propagation in the zebrafish was measured using a high frequency 18 MHz ultrasound probe. Shear wave speeds were measured at 300, 400, and 500 Hz. Shear wave speeds were, respectively, 3.13 ± 1.20 (m/s) for 300 Hz, 4.28 ± 1.36 (m/s) for 400 Hz, and 5.07 ± 1.45 (m/s) for 500 Hz for zebrafish 1 in a region of interest (ROI) which covered the central body. The shear wave speed dispersions were similar for four zebrafish and shear wave speeds ranged between 2.5 (m/s) and 5 (m/s) from 300 Hz to 500 Hz. The experimental setup and testing for a zebrafish lasted less than three minutes. All tested zebrafish were alive after testing. ZUVE is safe, fast, and noninvasive, making the testing of elastic properties of zebrafish feasible., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The ever-increasing demand for natural products and biotechnology derived from bees and ultra-modernization of various analytical devices has facilitated the rational and planned development of biotechnology products with a focus on human health to treat chronic and neglected diseases. The aim of the present study was to prepare and characterize polymeric nanoparticles loaded with Brazilian red propolis extract and evaluate the cytotoxic activity of "multiple-constituent extract in co-delivery system" for antileishmanial therapies. The polymeric nanoparticles loaded with red propolis extract were prepared with a combination of poly-ε-caprolactone and pluronic using nanoprecipitation method and characterized by different analytical techniques, antioxidant and leishmanicidal assay. The red propolis nanoparticles in aqueous medium presented particle size (200-280 nm) in nanometric scale and zeta analysis (-20 to -26 mV) revealed stability of the nanoparticles without aggregation phenomenon during 1 month. After freeze-drying method using cryoprotectant (sodium starch glycolate), it was possible to observe particles with smooth and spherical shape and apparent size of 200 to 400 nm. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and thermal analysis revealed the encapsulation of the flavonoids from the red propolis extract into the polymeric matrix. Ultra performance liquid chromatography coupled with diode array detector (UPLC-DAD) identified the flavonoids liquiritigenin, pinobanksin, isoliquiritigenin, formononetin and biochanin A in ethanolic extract of propolis (EEP) and nanoparticles of red propolis extract (NRPE). The efficiency of encapsulation was determinate, and median values (75.0 %) were calculated using UPLC-DAD. 2,2-Diphenyl-1-picryhydrazyl method showed antioxidant activity to EEP and red propolis nanoparticles. Compared to negative control, EEP and NRPE exhibited leishmanicidal activity with an IC50 value of ≅38.0 μg/mL and 31.3 μg/mL, 47.2 μg/mL, 154.2μg/mL and 193.2 μg/mL for NRPE A1, NRPE A2, NRPE A3 and NRPE A4, respectively. Nanoparticles loaded with red propolis extract in co-delivery system and EEP presented cytotoxic activity on Leishmania (V.) braziliensis. Red propolis extract loaded in nanoparticles has shown to be potential candidates as intermediate products for preparation of various pharmaceutical dosage forms containing red propolis extract in the therapy against negligible diseases such as leishmaniasis. Graphical Abstract Some biochemical mechanisms of cellular debridement of Leishmania (V.) braziliensis species by the flavonoids of red propolis extract (EEP) or NRPE loaded with red propolis extract.

Although a flow cytometer, being one of the most popular research and clinical tools for biomedicine, can analyze cells based on the cell size, internal structures such as granularity, and molecular markers, it provides little information about the physical properties of cells such as cell stiffness and physical interactions between the cell membrane and fluid. In this paper, we propose a computational cell analysis technique using cells' different equilibrium positions in a laminar flow. This method utilizes a spatial coding technique to acquire the spatial position of the cell in a microfluidic channel and then uses mathematical algorithms to calculate the ratio of cell mixtures. Most uniquely, the invented computational cell analysis technique can unequivocally detect the subpopulation of each cell type without labeling even when the cell type shows a substantial overlap in the distribution plot with other cell types, a scenario limiting the use of conventional flow cytometers and machine learning techniques. To prove this concept, we have applied the computation method to distinguish live and fixed cancer cells without labeling, count neutrophils from human blood, and distinguish drug treated cells from untreated cells. Our work paves the way for using computation algorithms and fluidic dynamic properties for cell classification, a label-free method that can potentially classify over 200 types of human cells. Being a highly cost-effective cell analysis method complementary to flow cytometers, our method can offer orthogonal tests in companion with flow cytometers to provide crucial information for biomedical samples.

Control over thrombin activity is much desired to regulate blood clotting in surgical and therapeutic situations. Thrombin-binding RNA and DNA aptamers have been used to inhibit thrombin activity and thus the coagulation cascade. Soluble DNA aptamers, as well as two different aptamers tethered by a flexible single-strand linker, have been shown to possess anticoagulant activity. Here, we link multiple aptamers at programmed positions on DNA nanostructures to optimize spacing and orientation of the aptamers and thereby to maximize anticoagulant activity in functional assays. By judicious engineering of the DNA nanostructures, we have created a novel, functional DNA nanostructure, which is a multi-aptamer inhibitor with activity eightfold higher than free aptamer. Reversal of the thrombin inhibition was also achieved by the use of single-stranded DNA antidotes, thus enabling significant control over blood coagulation., From the Clinical Editor: Thrombin inhibition via DNA aptamers has recently become a possibility. In this study, thrombin-binding DNA aptamers were further optimized by nanoscale organization on DNA nanostructures. The authors have created a novel, functional DNA nanostructure, which is a multi-aptamer inhibitor with activity eightfold higher than that of free aptamer. Reversal of thrombin inhibition was also achieved by single-stranded DNA antidotes, enabling significant control over the coagulation pathway., (Copyright © 2012. Published by Elsevier Inc.)

A total synthesis of the vancomycin aglycon 1 has eluded synthetic chemists for so many years that the preparation of this molecule has become a vendetta for some groups. Finally, and almost simultaneously, research teams led by Evans and by Nicolaou have succeeded. Similarities and differences in their synthetic approaches are highlighted herein., (© 1999 WILEY-VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany.)