The COVID-19 pandemic has shaken the world since early 2020 and its health, social, economic, and societal negative impacts at the global scale have been catastrophic. Since the early days of the ...pandemic, development of safe and effective vaccines was judged to be the best possible tool to minimize the effects of this pandemic. Drastic public health measures were put into place to stop the spread of the virus, with the hope that vaccines would be available soon. Thanks to the extraordinary commitments of many organizations and individuals from around the globe and the collaborative effort of many international scientists, vaccines against COVID-19 received regulatory approval for emergency human use in many jurisdictions in less than a year after the identification of the viral sequence. Several of these vaccines have been in use for some time; however, the pandemic is still ongoing and likely to persist for the foreseeable future. This is due to many reasons including reduced compliance with public health restrictions, limited vaccine manufacturing/distribution capacity, high rates of vaccine hesitancy, and the emergence of new variants with the capacity to spread more easily and to evade current vaccines. Here we discuss the discovery and availability of COVID-19 vaccines and evolving issues around mass vaccination programs.
Therapeutic antibody technology heavily dominates the biologics market and continues to present as a significant industrial interest in developing novel and improved antibody treatment strategies. ...Many noteworthy advancements in the last decades have propelled the success of antibody development; however, there are still opportunities for improvement. In considering such interest to develop antibody therapies, this review summarizes the array of challenges and considerations faced in the design, manufacture, and formulation of therapeutic antibodies, such as stability, bioavailability and immunological engagement. We discuss the advancement of technologies that address these challenges, highlighting key antibody engineered formats that have been adapted. Furthermore, we examine the implication of novel formulation technologies such as nanocarrier delivery systems for the potential to formulate for pulmonary delivery. Finally, we comprehensively discuss developments in computational approaches for the strategic design of antibodies with modulated functions.
IntroductionThe Prospective Physical Activity Sitting and Sleep consortium (ProPASS) is an international collaboration platform committed to harmonise thigh-worn accelerometry data. The aim of this ...paper is to (1) outline observational thigh-worn accelerometry studies and (2) summarise key strategic directions arising from the inaugural ProPASS meeting.Methods(1) We performed a systematic scoping review for observational studies of thigh-worn triaxial accelerometers in free-living adults (n≥100, 24 hours monitoring protocols). (2)Attendees of the inaugural ProPASS meeting were sent a survey focused on areas related to developing ProPASS: important terminology (Q1); accelerometry constructs (Q2); advantages and distinct contribution of the consortium (Q3); data pooling and harmonisation (Q4); data access and sharing (Q5 and Q6).Results(1) Eighty eligible articles were identified (22 primary studies; n~17 685). The accelerometers used most often were the ActivPAL3 and ActiGraph GT3X. The most commonly collected health outcomes were cardiometabolic and musculoskeletal. (2) None of the survey questions elicited the predefined 60% agreement. Survey responses recommended that ProPASS: use the term physical behaviour or movement behaviour rather than ‘physical activity’ for the data we are collecting (Q1); make only minor changes to ProPASS’s accelerometry construct (Q2); prioritise developing standardised protocols/tools (Q4); facilitate flexible methods of data sharing and access (Q5 and Q6).ConclusionsThigh-worn accelerometry is an emerging method of capturing movement and posture across the 24 hours cycle. In 2020, the literature is limited to 22 primary studies from high-income western countries. This work identified ProPASS’s strategic directions—indicating areas where ProPASS can most benefit the field of research: use of clear terminology, refinement of the measured construct, standardised protocols/tools and flexible data sharing.
To develop novel antimycobacterial agents, a new series of thiazolidinone-azole hybrids 4a-b, 5a-b and 6-13 were designed and synthesized. Thiazolidin-4-ones (4a-b and 5a-b) were obtained by the ...reaction of
bases and hydrazones (2a-b and 3a-b) with mercaptoacetic acid. 5-Benzylidene derivatives (6-13) were gained by treatment of 5a-b with appropriate benzaldehydes according to
condensation. To evaluate their structures
H NMR, IR, mass spectrometry and elemental analysis data were used. The target compounds were screened for their antimycobacterial activity against M. tuberculosis H37Rv strain using the microplate alamar blue assay method. Among them, 6, 10 and 12 (MIC: 14.27-14.74 μM) were found as most active compounds in the series. It was seen that both phenylamino and benzylidene substitutions on thiazolidin-4-one ring caused an improvement in the antimycobacterial activity.
Intakes are used to take water from reservoirs, lakes, and oceans. Depending on flow and geometrical conditions in which the intakes are located, sediment particles may also be entrained by the ...intake flow, resulting in a scour hole. Characteristics of scour hole are affected by the bed sediment properties, intake discharge, and intake position with respect to flow boundaries (i.e., dead-end wall, channel bottom, channel side walls). In this study, experiments were conducted to investigate the effects of the intake discharge, sediment size, and intake position relative to flow boundaries on scour hole characteristics. Entrainment conditions of sediment particles at the bed of the channel were also examined. Experimental results indicated that the maximum scour depth along the centerline of the channel was mostly affected by the sub-surface vortices extending from the channel bed to the intake. As the distance between the dead-end wall and the intake center decreased, the strength of the sub-surface vortices also decreased due to the effect of the friction imposed by the dead-end wall on the sub-surface vortices. Furthermore, the width and length of the scour hole decreased as the distance between the intake center and the dead-end wall increased.
•Effects of flow boundaries on the scour mechanism were investigated.•Sub-surface vortex was effective on maximum scour depth.•Velocity effect becomes important in terms of extent of the scour hole.•Equations were proposed for scour hole characteristics.•Conditions for sediment entrainment to intake were established.
In the present study, the capabilities of different chip materials for acoustic particle manipulation have been assessed with the same microfluidic device architecture, under the same actuator and ...flow conditions. Silicon, glass, epoxy with fiberglass filling (FR4), polydimethylsiloxane (PDMS) and polymethyl methacrylate (PMMA) are considered as chip materials. The acoustophoretic chips in this study were manufactured with four different fabrication methods: plasma etching, chemical etching, micromachining and molding. A novel chip material, FR4, has been employed as a microfluidic chip material in acoustophoretic particle manipulation for the first time in literature, which combines the ease of manufacturing of polymer materials with improved acoustic performance. The acoustic particle manipulation performance is evaluated through acoustophoretic focusing experiments with 2μm and 12μm polystyrene microspheres and cultured breast cancer cell line (MDA-MB-231). Unlike the common approach in the literature, the piezoelectric materials were actuated with partitioned cross-polarized electrodes which allowed effective actuation of different family of chip materials. Different from previous studies, this study evaluates the performance of each acoustophoretic device through the perspective of synchronization of electrical, vibrational and acoustical resonances, considers the thermal performance of the chip materials with their effects on cell viability as well as manufacturability and scalability of their fabrication methods. We believe our study is an essential work towards the commercialization of acoustophoretic devices since it brings a critical understanding of the effect of chip material on device performance as well as the cost of achieving that performance.
•Selection of chip material is critical in micro-acoustofluidics.•Manipulation performance of several different chip materials are investigated.•FR4 chip material combines the advantages of polymer acoustically hard chip materials.•For the first time in the literature, the effect of choice of chip material isF investigated through electrical, vibration, thermal and cell viability perspectives as well as ease of manufacturing and scalability.
Celecoxib (CXB) is a Biopharmaceutical Classification System (BCS) Class II molecule with high permeability that is practically insoluble in water. Because of the poor water solubility, there is a ...wide range of absorption and limited bioavailability following oral administration. These unfavorable properties can be improved using dry co-milling technology, which is an industrial applicable technology. The purpose of this study was to develop and optimize CXB nanoformulations prepared by dry co-milling technology, with a quality by design approach to maintain enhanced solubility, dissolution rate, and oral bioavailability. The resulting co-milled CXB composition using povidone (PVP), mannitol (MAN) and sodium lauryl sulfate (SLS) showed the maximum solubility and dissolution rate in physiologically relevant media. Potential risk factors were determined with an Ishikawa diagram, important risk factors were selected with Plackett-Burman experimental design, and CXB compositions were optimized with Central Composite design (CCD) and Bayesian optimization (BO). Physical characterization, intrinsic dissolution rate, solubility, and stability experiments were used to evaluate the optimized co-milled CXB compositions. Dissolution and permeability studies were carried out for the resulting CXB nanoformulation. Oral pharmacokinetic studies of the CXB nanoformulation and reference product were performed in rats. The results of in vitro and in vivo studies show that the CXB nanoformulations have enhanced solubility (over 4.8-fold (8.6 ± 1.06 µg/mL vs. 1.8 ± 0.33 µg/mL) in water when compared with celecoxib pure powder), and dissolution rate (at least 85% of celecoxib is dissolved in 20 min), and improved oral pharmacokinetic profile (the relative bioavailability was 145.2%, compared to that of Celebrex
, and faster t
3.80 ± 2.28 h vs. 6.00 ± 3.67 h, indicating a more rapid absorption rate).
Anomalous origin of the circumflex coronary artery is extremely rare and may cause acute cardiac decompensation associated with correction of coexisting congenital malformations. We describe a ...10-year-old female patient who underwent surgical repair of the aortic coarctation at 4 years of age. Six years later, she presented with chest pain during exercise. Cardiac catheterization demonstrated 25 mmHg subaortic systolic gradient and retrograde filling of the circumflex coronary artery from the left anterior descending and right coronary artery, with drainage into the right pulmonary artery. Reimplantation of the anomalous circumflex coronary artery to the aorta and resection of subaortic fibrous membrane was performed. Her postoperative course was uneventful, with complete relief of symptoms.
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