Geometrical and Hemodynamic Variables for Thrombotic Risk Stratification in Kawasaki Disease

Objectives Thrombosis is a major adverse outcome for coronary artery aneurysms (CAA) in Kawasaki disease (KD). We investigated the geometric and hemodynamic abnormalities in patients with CAA and identified the risk factors for thrombosis by computational fluid dynamics (CFD) simulation. Methods We retrospectively studied 27 KD patients with 77 CAAs, including 20 CAAs with thrombosis in 12 patients. Patient-specific anatomic models obtained from cardiac magnetic resonance imaging (CMRI) were constructed to perform a CFD simulation. From the simulation results, we produced local hemodynamic parameters comprising of time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI) and relative resident time (RRT). The CAA’s maximum diameter (Dmax) and Z-score were measured on CMRI. Results Giant CAAs tended to present with more severe hemodynamic abnormalities. Thrombosed CAAs exhibited lower TAWSS (1.551 ± 1.535 vs. 4.235 ± 4.640dynes/cm2, p = 0.002), higher Dmax (10.905 ± 4.125 vs. 5.791 ± 2.826mm, p = 0.008), Z-score (28.301 ± 13.558 vs. 13.045 ± 8.394, p = 0.002), OSI (0.129 ± 0.132 vs. 0.046 ± 0.080, p = 0.01), and RRT (16.780 ± 11.982s vs. 9.123 ± 11.770s, p = 0.399) than the non-thrombosed group. An ROC analysis for thrombotic risk proved that all of the five parameters had area under the ROC curves (AUC) above 0.7, with Dmax delineating the highest AUC (AUCDmax = 0.871) and a 90% sensitivity, followed by Z-score (AUCZ−score = 0.849). Conclusions It is reasonable to combine the geometric index with hemodynamic information to establish a severity classification for KD cases.

Development of Integrated Electrocoagulation-Sedimentation (IECS) in Continuous Mode for Turbidity and Color Removal

The present work focused on the development and evaluation of a compact electrocoagulation (EC) reactor, combined between EC and clarifier processes in continuous modes for decolorization and turbidity removal, named the integrated electrocoagulation-sedimentation reactor (IECS). The experiments were firstly conducted in the four-liter batch column in order to optimize the EC configuration and operation condition. The removal kinetics were also investigated and predicted for kinetic correlations. After various optimization steps, the IECS reactor was conducted, consisting of EC and clarifier compartments. Liquid flow pattern in EC compartment was examined through resident time distribution technique for defining the number of EC units and divided baffles. In summary, four units of EC were placed in the EC compartment of the IECS reactor with 90% in the width of three baffles. Each EC unit had two pairs of aluminum electrode plats in monopolar arrangement with a 1.5 cm gap and required a current density of 13.5 mA/cm2. For the clarifier compartment, it was mainly designed based on the batch settling test for separating the precipitated particles. The treatment performance of the IECS reactor was tested at different liquid flows in order to reduce the pollutant to a certain level. For the individual condition, liquid flow rates of 3 and 1 L/min were defined for turbidity and color, respectively. If both pollutants are presented simultaneously, a liquid flow rate of 1–2 L/min can be used for decreasing turbidity from 250 to <20 NTU and color from 6000 to <300 ADMI.

Discovery of Highly Potent Fusion Inhibitors with Potential Pan-Coronavirus Activity That Effectively Inhibit Major COVID-19 Variants of Concern (VOCs) in Pseudovirus-Based Assays

We report the discovery of several highly potent small molecules with low-nM potency against severe acute respiratory syndrome coronavirus (SARS-CoV; lowest half-maximal inhibitory concentration (IC50: 13 nM), SARS-CoV-2 (IC50: 23 nM), and Middle East respiratory syndrome coronavirus (MERS-CoV; IC50: 76 nM) in pseudovirus-based assays with excellent selectivity index (SI) values (>5000), demonstrating potential pan-coronavirus inhibitory activities. Some compounds showed 100% inhibition against the cytopathic effects (CPE; IC100) of an authentic SARS-CoV-2 (US_WA-1/2020) variant at 1.25 µM. The most active inhibitors also potently inhibited variants of concern (VOCs), including the UK (B.1.1.7) and South African (B.1.351) variants and the Delta variant (B.1.617.2) originally identified in India in pseudovirus-based assay. Surface plasmon resonance (SPR) analysis with one potent inhibitor confirmed that it binds to the prefusion SARS-CoV-2 spike protein trimer. These small-molecule inhibitors prevented virus-mediated cell–cell fusion. The absorption, distribution, metabolism, and excretion (ADME) data for one of the most active inhibitors, NBCoV1, demonstrated drug-like properties. An in vivo pharmacokinetics (PK) study of NBCoV1 in rats demonstrated an excellent half-life (t1/2) of 11.3 h, a mean resident time (MRT) of 14.2 h, and oral bioavailability. We expect these lead inhibitors to facilitate the further development of preclinical and clinical candidates.

Study on hourly temperature features over Mumbai, Thiruvananthapuram and Minicoy during 1969-2012

Amongst all the climatic elements, temperature plays a major role in detecting and analyzing climatic change and its impact. The variability in resident time of the surface temperature is studied to investigate whether any change in temperature has taken place. Analysis of the results is presented for Mumbai, a mega city with large change in land-use pattern, Thiruvananthapuram, a semi-urban city with moderate changes in land-use pattern and Minicoy, an Island city without much change in land-use pattern. These three places representing varying geographical locations and climatic conditions are unique in nature, however having uniform maritime influence. It is revealed that the change is large in Mumbai in comparison with others as expected. The study proposes a new methodology based on the resident time of temperatures and its trend and could be used as a tool for relative ranking of cities and to gauge the source and sink regions of climate change forcing. The resident time of temperatures shows increasing trend above the mean temperature and decreasing trend below the mean temperature of the initial decade. Decadal linear increasing trends in mean temperatures are 0.256 °C, 0.159 °C and 0.146 °C per decade for Mumbai, Thiruvananthapuram and Minicoy respectively. This confirms the effect of global warming unequivocally irrespective of urban effect. Decadal linear increasing trends in mean temperature during non-monsoon season for Mumbai, Thiruvananthapuram and Minicoy are 0.315 °C, 0.155 °C and 0.181 °C per decade respectively. The rate of increase of mean temperature for Mumbai and Minicoy during monsoon season is 0.143 °C and 0.081 °C per decade respectively, are significantly less than the decadal trend in annual mean, which suggests that rainfall activity seems to be the correction factor for the increasing trend in the annual mean temperature which otherwise would have been a higher value. However, the rate of increase of mean temperature for Thiruvananthapuram during monsoon season for the study period is 0.172 °C per decade, which is slightly higher than the decadal trend in annual mean. Noticeable changes in resident time during monsoon season are in conformity with change in rainfall patterns.

Discovery of highly potent pancoronavirus fusion inhibitors that also effectively inhibit COVID-19 variants from the UK and South Africa

We report the discovery of a series of benzoic acid-based inhibitors that show highly potent pancoronavirus activity. Some compounds also show complete inhibition of CPE (IC100) at 1.25 μM against an authentic SARS-CoV-2 (US_WA-1/2020). Furthermore, the most active inhibitors also potently inhibited variants initially identified in the UK and South Africa. We confirmed that one of the potent inhibitors binds to the prefusion spike protein trimer of SARS-CoV-2 by SPR. Besides, we showed that they inhibit virus-mediated cell-cell fusion. The ADME data show druglike characteristics, and in vivo PK in rats demonstrated excellent half-life (t½) of 11.3 h, mean resident time (MRT) of 14.2 h, and orally bioavailable. Despite the presence of ene-rhodamine moiety, we conclusively demonstrated that these inhibitors target the viral spike protein and are not promiscuous or colloidal aggregators. We expect the lead inhibitors to pave the way for further development to preclinical and clinical candidates.

In-Situ Forming Polymeric Drug Delivery Systems for Ophthalmic Use: An Overview

Delivery of drug into the ocular region is hindered by the protective layers that encapsulate the eyes, it has always been a major problem to get an effective bioavailability of the active drug in the ocular region due to the low precorneal resident time of most of the ocular delivery systems specifically convention once such as ointment, solution and suspension, as a result, most of the delivery systems are not capable of effectively treating ocular diseases. Several works have and are being carried out to overcome this problem one of which is using in-situ forming polymeric systems. Ocular In-situ gelling systems are a novel class of ocular drug delivery systems that are initially in a solution form but instantaneously gets converted into a viscous gel upon introduction or installation in the ocular cavity from which the active drugs get released in a sustained manner. This sol-to-gel phase transition depends upon various factors like change in pH, ion presence and change in temperature. Gel formed after the transformation has preferred viscosity along with bio-adhesive property, which increases the gel’s resident time in the ocular area and also releases the drug in a prolonged and sustained manner unlike conventional eye drops and ointments. This review emphasizes various ocular in-situ systems namely, pH triggered, Ion activated, and Temperature triggered systems which have prolonged residence time in the cul-de-sac area of the eye, hence increasing the ocular bioavailability. Keywords: In-situ gel, Ocular Drug delivery, Ocular Bioavailability, Polymer

Evaluate the impact of hydrodynamic pressure on hydrologic exchange fluxes and resident time for a large-scale river section over a long-term period

Quantifying hydrologic exchange fluxes (HEF) and subsurface water residence times (RT) are important for managing the water quality and ecosystem health in dynamic river corridor systems. Laboratory-scale experiments and models have shown that hydrodynamic pressure variations on the riverbed induced by dynamic river flows can strongly impact HEFs and RTs. In this study, the impacts of hydrodynamic pressure on HEFs and RT for a 30 km section of the Columbia River in Washington State over a three-year period were quantitatively evaluated using a coupled transient three-dimensional (3D) multi-phase surface and subsurface water flow transport approach. Based on comparisons between model simulations with and without considering hydrodynamic pressure, we found that hydrodynamic pressure increase the net HEFs by 7% of flowing into river from subsurface domain, and also leads to a reduction of the area with long RT, and increase of area with short RT.

Analyzing Anatomic Pathology On-Call Summaries to Improve Resident Education

Context.— Pathology on-call experiences help prepare trainees for successful transition from residency to independent practice, and as such are an integral component of training. However, few data exist on anatomic pathology resident on-call workload and experience. Objective.— To obtain an overall picture of the anatomic pathology on-call experience to inform and improve resident education. Design.— Retrospective and prospective review of the daily anatomic pathology on-call summaries from July 2016 to June 2020. Results.— During the first 2 years of the study (ie, retrospective portion), only 19% of on-call summaries (138 of 730) were available for review. After interventions, the on-call summary submission rate jumped to 98% (716 of 731). After-hours calls were most frequent on weekdays from 5 to 8 pm. The most frequent requests were for frozen sections (55%; 619 of 1125 calls), inquiries regarding disposition of fresh placentas (13%; 148 of 1125 calls), and inquiries regarding disposition of various other specimens (6%; 68 of 1125 calls). After-hours frozen section requests were most frequent for gynecologic and head and neck specimens. Notably, a significant number of after-hours calls were recurring preanalytic issues amenable to system-level improvements. We were able to eliminate the most common of these recurring preanalytic calls with stepwise interventions. Conclusions.— To our knowledge, this is the first study analyzing the anatomic pathology resident on-call experience. In addition to obtaining a broad overview of the residents' clinical exposure on this service, we identified and resolved issues critical to optimal patient care (eg, inconsistent “patient hand-off”) and improved the resident on-call experience (eg, fewer preanalytic calls increased resident time for other clinical, educational, or wellness activities).

Adsorption Kinetics of Various Frothers on Rising Bubbles of Different Sizes under Flotation Conditions

This paper studies the effect of the type and concentration of selected frothers, the gas flowrate, and the pore size of the porous frit on the bubble sizes (Sauter mean diameter, SMD) of bubbling flow produced in a micro-flotation cell, and the determination of bubble size distribution (BSD) in the presence of the frothers. The commercial frothers polypropylene glycols (PPG 200, 400, and 600), tri propylene glycol (BTPG), triethylene glycol (BTEG), dipropylene glycol (BDPG), and Methyl Isobutyl Carbinol (MIBC) were used in the present investigation. The frother concentration varied from 1 to 1000 ppm. The flow rate varied in the range of 25 to 100 cm3/min. The pore sizes of the frit were selected as 10–16 μm, 16–40 μm, and 40–100 μm. Each frother exhibited its own unique ability in preventing coalescence of the bubbles in the order of BTEG < BDPG < PPG 200 < MIBC < BTPG < PPG 400 < PPG 600. The factorial experiments established that the type of the frother and its concentration have a major effect on the size of the bubbles. The bubbles decreased twice their size when the frother concentration was increased from 1 ppm to 1000 ppm. The pore size of the frit is a significant factor as well. The size of the bubbles can be reduced from about 10% to about 40% by decreasing the pores from 40–100 μm to 10–16 μm but the level of this decrease depends on the type of the frother. The increase of the flowrate from 25 cm3/min to 100 cm3/min produced bubbles smaller by 25% to 50% for the case of BTEG, BDPG, PPG 200, MIBC, BTPG, while a minimum of the bubble sizes was reached for the case of PPG 400 and PPG 600, beyond which the bubbles enlarged their size. The BSD in the presence of PPG 600 varied around 0.3 mm, whereas BTEG gave a wider BSD which indicated that the type of frother affected the bubble production. Our analysis shows that the first group of frothers adsorbs instantly on the bubbles, once they leave the porous frit, thus reaching equilibrium. PPG 400 and PPG 600 adsorb significantly slower on the bubbles, possibly not reaching equilibrium during their resident time.

Educational Informed Consent Video Equivalent to Standard Verbal Consent for Rhinologic Surgery: A Randomized Controlled Trial

Background Informed consent is an integral part of pre-operative counseling. However, information discussed can be variable. Recent studies have explored the use of multimedia in providing informed consent for rhinologic surgery. Objective To measure impact of an educational video (Video) compared to verbal informed consent (Verbal) on knowledge gained, alleviation of concerns, and efficiency. Methods Patients undergoing endoscopic sinus surgery (ESS), septoplasty, or ESS+septoplasty were prospectively enrolled and randomized to receive Video or Verbal consent. The Video group watched an educational video; the Verbal group received standard verbal consent from an Otolaryngology resident per institutional protocol. Both groups had the opportunity to discuss questions or concerns with their attending surgeon. Prior to, and after, consent was signed, both groups completed surveys regarding knowledge of purpose, risks, and benefits of surgery as well as surgical concerns. Decision regret and patient satisfaction were also assessed post-operatively. Results 77 patients were enrolled (39 Video, 38 Verbal). Demographics were not significantly different between groups. Overall knowledge significantly improved (p < 0.005) and concerns significantly decreased (p < 0.001) following consent in both groups. Improvements in these metrics were equivalent between groups (p < 0.02). Furthermore, resident time to complete consent, patient satisfaction, and decision regret were not significantly different between groups. Conclusion Use of an educational video was equivalent to standard verbal informed consent for patients undergoing rhinologic surgery. Otolaryngologists can consider developing procedure-specific videos to allow allocation of time to other tasks, standardized education of patients, and streamlining of the informed consent process.