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Introduction. The author provides data about coming into being of Uzbek and Azerbaijani scientific collaboration during the years of independent development of the two countries. The article deals with solid contractual basis in the scientific sphere, including the agreements between the Ministries of Public Education, Academies of Sciences, higher education institutions of the two countries, and with the collaboration in the field of the attestation of highly-qualified scientific and scientific-pedagogical personnel. Methods and materials. The given article also contains information about the direct co-operation of the two states in the sphere of natural, exact sciences and humanities, furthering close and fruitful interrelation of the two countries’ scientific circles, covering all the given sphere’s branches of partnership relations. Analysis. The article analyzes the process of multifaceted scientific cooperation between Uzbekistan and Azerbaijan, which occurs through the establishment of close contacts between scientists and research centers of the two countries, the implementation of joint research on pressing issues, mutual internships and scientific business trips, as well as the participation in international scientific conferences and symposiums. Close mutual contacts are also carried out in the form of the exchange of scientific personnel and work. Results. The multifaceted Uzbek-Azerbaijani scientific cooperation considered in the article is represented by the following factors: bilateral agreements and arrangements in the scientific field; direct development in the field of natural, exact sciences and humanities; implementation of mutual internships and scientific missions; exchange of scientific personnel and labor.

Three groups of subjects, seven subjects each, were required, to perform a central tracking task and simultaneously respond to peripheral stimuli, while being exposed to heat stress environments. One group was exposed to a 95°F and 50% RH environment, the second group was exposed to a 95°F and 75% RH environment, and the third group was exposed to a 100°F and 50% RH environment. The performance results showed that there was a significant deterioration in tracking and increase in reaction time only when the subjects were exposed to the 95°F and 75% RH environment. The peripheral field of awareness was not significantly affected by any of the three environments. [ABSTRACT FROM PUBLISHER]

Bioreactor parameters can have significant effects on the quantity and quality of biotherapeutics. Monoclonal antibody products have one particularly important critical quality attribute being the distribution of product glycoforms. N-linked glycosylation affects the therapeutic properties of the antibody including effector function, immunogenicity, stability, and clearance rate. Our past work revealed that feeding different amino acids to bioreactors altered the productivity and glycan profiles. To facilitate real-time analysis of bioreactor parameters and the glycosylation of antibody products, we developed an on-line system to pull cell-free samples directly from the bioreactors, chemically process them, and deliver them to a chromatography-mass spectroscopy system for rapid identification and quantification. We were able to successfully monitor amino acid concentration on-line within multiple reactors, evaluate glycans off-line, and extract four principal components to assess the amino acid concentration and glycosylation profile relationship. We found that about a third of the variability in the glycosylation data can be predicted from the amino acid concentration. Additionally, we determined that the third and fourth principal component accounts for 72% of our model's predictive power, with the third component indicated to be positively correlated with latent metabolic processes related to galactosylation. Here we present our work on rapid online spent media amino acid analysis and use the determined trends to collate with glycan time progression, further elucidating the correlation between bioreactor parameters such as amino acid nutrient profiles, and product quality. We believe such approaches may be useful for maximizing efficiency and reducing production costs for biotherapeutics., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA. Biotechnology Progress published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Most therapeutic proteins are glycosylated with N-glycans and/or O-glycans. N-glycans on therapeutic proteins have been extensively studied for their control strategy and impact on drug product quality. However, knowledge of O-glycosylation in therapeutic protein production and its impact on product quality remains elusive. To address this gap, we generated an O-glycoengineered Chinese Hamster Ovary (CHO) cell line platform to modulate O-glycosylation of therapeutic proteins and investigated the impact of O-glycans on the physicochemical and biological properties of etanercept. Our results demonstrate that this CHO cell line platform produces controlled O-glycosylation profiles containing either truncated O-glycans (sialylTn and/or Tn), or sialylCore 3 alone, or sialylCore 1 with sialylTn or sialylCore 3 O-glycans on endogenous and recombinant proteins. Moreover, the platform demonstrated exclusive modulation of O-glycosylation without affecting N-glycosylation. Importantly, certain O-glycans on etanercept enhanced tumor necrosis factor-α binding affinity and consequent potency. This is the first report that describes the systematic establishment of an O-glycoengineered CHO cell line platform with direct evidence that supports the applicability of the platform in the production of engineered proteins with desired O-glycans. This platform is valuable for identifying O-glycosylation as a critical quality attribute of biotherapeutics using the quality by design principle., Competing Interests: The authors have no interests to declare. The funding source had no part in the study design, data collection/analysis, decision to publish, or preparation of the manuscript. The authors have no conflicts of interests. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the United States Food and Drug Administration and the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government.

Primary clarification is an essential step in a biomanufacturing process for the initial removal of cells from therapeutic products within the harvested cell culture fluid. While traditional methods like centrifugation or filtration are widely implemented for cell removal, the equipment for these processes have large footprints and operation can involve contamination risks and filter fouling. Additionally, traditional methods may not be ideal for continuous bioprocessing schemes for primary clarification. Thus, an alternate application using acoustic (sound) waves was investigated to continuously separate cells from the cell culture fluid. Presented in this study is a detailed protocol for using a bench-scale acoustic wave separator (AWS) for the primary separation of culture fluid containing a monoclonal IgG1 antibody from a CHO cell bioreactor harvest. Representative data are presented from the AWS and demonstrate how to achieve effective cell clarification and product recovery. Finally, potential applications for AWS in continuous bioprocessing are discussed. Overall, this study provides a practical and general protocol for the implementation of AWS in primary clarification for CHO cell cultures and further describes its application potential in continuous bioprocessing.

Objective: Children with attention-deficit hyperactivity disorder (ADHD) have ongoing needs that impair home and school functioning. Group visit models are a promising way to deliver timely parenting support but family and provider acceptance has not previously been examined. The objective was to describe the acceptability of ADHD group visits in busy pediatric clinics based on caregivers, child participants and facilitators., Methods: Data were analyzed from school-age children and caregivers who participated in one of two 12-month long randomized controlled studies of the ADHD group visit model from 2012 to 2013 or 2014 to 2015. Feedback was obtained using semi-structured questions at each study end, by telephone or at the last group visit. Sessions were audio-recorded, transcribed and themes were extracted by participant type., Results: A total of 34 caregivers, 41 children and 9 facilitators offered feedback. Caregivers enjoyed the "support group" aspect and learning new things from others. Caregivers reported improved understanding of ADHD and positive changes in the relationship with their child. Children were able to recall specific skills learned including how skills helped at home or school. Facilitators acknowledged systems-level challenges to offering group visits but felt the group format helped increase understanding of families' needs, improved overall care, and provided innovative ways to engage with families., Conclusion: The majority of comments from families and facilitators highlighted a variety of benefits of the use of a group visit model for ADHD chronic care. Despite systems-level barriers to implementation, families and facilitators felt the benefits outweighed the challenges.

Background: The increased use of information technology supports a resident- centred educational approach that promotes autonomy, flexibility and time management and helps residents to assess their competence, promoting self-awareness. We established a web-based e-learning tool to introduce general surgery residents to bariatric surgery and evaluate them to determine the most appropriate implementation strategy for Internet-based interactive modules (iBIM) in surgical teaching., Methods: Usernames and passwords were assigned to general surgery residents at the University of Alberta. They were directed to the Obesity101 website and prompted to complete a multiple-choice precourse test. Afterwards, they were able to access the interactive modules. Residents could review the course material as often as they wanted before completing a multiple-choice postcourse test and exit survey. We used paired t tests to assess the difference between pre- and postcourse scores., Results: Out of 34 residents who agreed to participate in the project, 12 completed the project (35.3%). For these 12 residents, the precourse mean score was 50 ± 17.3 and the postcourse mean score was 67 ± 14 (p = 0.020)., Conclusion: Most residents who participated in this study recommended using the iBIMs as a study tool for bariatric surgery. Course evaluation scores suggest this novel approach was successful in transferring knowledge to surgical trainees. Further development of this tool and assessment of implementation strategies will determine how iBIM in bariatric surgery may be integrated into the curriculum.

Background: Over 1.7 billion adults worldwide are considered overweight or obese, with the prevalence of obesity in Canada increasing rapidly. Obesity has been shown to affect surgical outcomes such as local recurrence of cancer and wound infections following colorectal surgery. The objective of this study was to determine the perception/attitudes of Canadian surgeons toward the impact of obesity on the practice of colorectal surgery., Methods: A twenty-question survey was administered to Canadian surgeons through mail and email solicited via the Canadian Association of General Surgeons over a period of 2010-2011. The questions focused on surgeon demographics, experience with laparoscopic colon resections and their perception of the impact of obesity toward surgical proficiency and complications., Results: One hundred seventy-seven Canadian surgeons completed the survey. There was a wide range of experience among surgeons in terms of years of practice and number of colon resections performed per year. The majority (72.9%) reported having primary general surgical training. A majority of surgeons (57.7%) identified obesity as a risk factor for colorectal surgery. Furthermore, a majority agreed that obesity is a risk factor for wound infection (97.2%), stomal retraction (90.4%) and stomal herniation (82.5%). While obesity was not considered a contraindication to laparoscopic colon surgery, it was considered to increase operative time (98.3%), cardiovascular (80.2%) and respiratory (95.4%) complications., Conclusion: The majority of surgeons across Canada believe obesity is a risk factor for post-operative complications following laparoscopic colorectal surgery. However, the majority did not consider obesity a contraindication for laparoscopic colon resection. Surgical and peri-operative colorectal protocols may need to be re-assessed to identify methods to manage the obese patient more effectively.

Dispersal delays are introduced into a competition model for two species that disperse among n identical patches. The model is formulated as a system of integro-differential equations with an arbitrary distribution of dispersal times between patches. By identifying steady states and analyzing local stability, conditions for competitive exclusion, coexistence or extinction are determined in terms of the system parameters. These are confirmed by numerical simulations with a delta function distribution, showing that all solutions approach a steady state and that high dispersal is generally a disadvantage to a species. However, if the two species have identical local dynamics, then small dispersal rates (with certain parameter restrictions) can be an advantage to the dispersing species. If the number of species is increased to three, then oscillatory coexistence with dispersal delay is possible.

The total synthesis of pyrrolizidines 223H', 239K', 265H', and 267H' has been achieved starting from 1,5-hexadiene via a common synthetic intermediate 5. The affinity of 1-4 for nicotinic acetylcholine receptor was evaluated.

An automated flow fluorometer designed for kinetic binding analysis was adapted to develop a solid-phase competitive fluoroimmunoassay for urinalysis of opiates. The solid phase consisted of polymer beads coated with commercial monoclonal antibodies (MAbs) raised against morphine. Fluorescein-conjugated morphine (FL-MOR) was used as the fluorescein-labeled hapten. The dissociation equilibrium constant (K(D)) for the binding of FL-MOR to the anti-MOR MAb was 0.23 nM. The binding of FL-MOR to the anti-MOR MAb reached steady state within minutes and was displaced effectively by morphine and other opiates. Morphine-3-glucuronide (M3G), the major urinary metabolite of heroin and morphine, competed effectively with FL-MOR in a concentration-dependent manner for binding to the antimorphine MAb and was therefore used to construct the calibration curve. The sensitivity of the assay was 0.2 ng/mL for M3G. The assay was effective at concentrations of M3G from 0.2 to 50 ng/mL, with an IC50 of 2 ng/mL. Other opiates and heroin metabolites that showed >50% crossreactivity when present at 1 microg/mL included codeine, morphine-6-glucuronide, and oxycodone. Methadone showed very low crossreactivity (<5%), which is a benefit for testing in patients being treated for opiate addictions. The high sensitivity of the assay and the relatively high cutoff value for positive opiate tests allows very small sample volumes (e.g., in saliva or sweat) to be analyzed. A double-blind comparison using 205 clinical urine samples showed good agreement between this single-step competitive assay and a commercially performed enzyme multiplied immunoassay technique for the detection of opiates and benzoylecgonine (a metabolite of cocaine).

A new solid phase fluoroimmunoassay using a fully automated flow fluorometer adapted for urinalysis of drug metabolites is described. Fluorescein-conjugated benzoylecgonine (FL-BE) and monoclonal antibodies (mAb) against benzoylecgonine (BE) were the reagents used for demonstration. The solid phase consisted of anti-BE mAbs immobilized on the surface of polymethyl methacrylate (PMMA) beads. Free BE in solution competed with FL-BE and reduced bead-bound fluorescence in a concentration-dependent manner. The binding of FL-BE to the anti-BE mAb reached steady-state within minutes. FL-BE was not bound by uncoated beads nor beads coated with non-specific proteins or IgG. The signal-to-noise ratio was 33, and the sensitivity of the assay was 2 ng ml(-1) for BE. The effective concentration of BE was 1 to 100 ng ml(-1), with an IC50 value of 12 ng ml(-1). The mAb showed equal affinities for BE, cocaine, and cocaethylene, but a five order-of-magnitude lower affinity for ecgonine and ecgonine methylester. In a double-blind comparison using clinical urine samples, the data from this single-step competitive assay had excellent agreement with results obtained using a fiber-optic biosensor (FOB), and the EMIT assay performed commercially. The assay provided kinetic data rapidly and can be used to detect small analytes for which antibodies and fluorescein conjugates are available. The affinity of the mAb for FL-BE, calculated from kinetic analysis of the time course of the on and off reaction, was 2.25 x 10(-9) M.