Continuous low-level dietary exposure to glyphosate elicits dose and sex-dependent synaptic and microglial adaptations in the rodent brain.

Prolonged exposure to low levels of dietary contaminants is a context in modern life that could alter organ physiology gradually. Here, we aimed to investigate the impact of continuous exposure to acceptable daily intake (ADI) and non-observable adverse effect level (NOAEL) of glyphosate from gestation to adulthood using C57BL/6J mice and incorporating these levels into their food pellets. From adulthood, we analyzed neurophysiological and neuro-glia cellular adaptations in male and female animals.

Subfunctionalisation of paralogous genes and evolution of differential codon usage preferences: The showcase of polypyrimidine tract binding proteins.

Gene paralogs are copies of an ancestral gene that appear after gene or full genome duplication. When two sister gene copies are maintained in the genome, redundancy may release certain evolutionary pressures, allowing one of them to access novel functions. Here, we focused our study on gene paralogs on the evolutionary history of the three polypyrimidine tract binding protein genes (PTBP) and their concurrent evolution of differential codon usage preferences (CUPrefs) in vertebrate species.

Concurrent schedules of differential reinforcement of alternative behavior in the treatment of problem behavior without extinction.

Differential reinforcement of alternative behavior (DRA) without extinction is an effective intervention for reducing problem behavior maintained by socially mediated reinforcement, particularly when implementing dense schedules of reinforcement for appropriate behavior. Thinning schedules of reinforcement for an alternative response may result in resurgence of problem behavior. Resurgence may be of particular concern in the treatment of problem behavior without extinction because problem behavior that resurges is also likely to encounter reinforcement and thus can be expected to maintain.

Enhanced neutralization escape to therapeutic monoclonal antibodies by SARS-CoV-2 omicron sub-lineages.

The landscape of SARS-CoV-2 variants dramatically diversified with the simultaneous appearance of multiple subvariants originating from BA.2, BA.4, and BA.

Synthesis of Imidazo[1,2-]pyridines: Triflic Anhydride-Mediated Annulation of 2-Azirines with 2-Chloropyridines.

The discovery and optimization of a reaction between 2-chloropyridines and 2-azirines producing imidazo[1,2-]pyridines is described. The treatment of 2-azirines with triflic anhydride (TfO) forms an electrophilic 1-trifloyl-aziridin-2-yl triflate species which, when reacted with 2-halopyridines, generates transient pyridinium salts. These salts were treated in the same pot with triethylamine (EtN), leading to the selective formation of C3-substituted imidazo[1,2-]pyridines, an heterocyclic moiety commonly found in medicinal chemistry leads and drugs.

Comparing the reinforcing efficacy of tokens and primary reinforcers.

Token economies are one of the most commonly used behavior-analytic interventions. Despite literature supporting the use of tokens as tools for behavior change, little is known about the efficacy of tokens compared to that of the items for which they are exchanged. Results of previous research comparing the reinforcing efficacy of tokens and primary reinforcers have shown that both produce similar effects on responding.

COUSIN (COdon Usage Similarity INdex): A Normalized Measure of Codon Usage Preferences.

Codon Usage Preferences (CUPrefs) describe the unequal usage of synonymous codons at the gene, chromosome, or genome levels. Numerous indices have been developed to evaluate CUPrefs, either in absolute terms or with respect to a reference. We introduce the normalized index COUSIN (for COdon Usage Similarity INdex), that compares the CUPrefs of a query against those of a reference and normalizes the output over a Null Hypothesis of random codon usage.

Producing mands in concurrent operant environments.

This study examined strategies designed to increase the rate of targeted, low-probability mands in a concurrent operant environment. We examined the effects of schedule manipulations, prompt manipulations, motivating operation manipulations, and combined behavioral process manipulations. Increases in target mands were produced for all 8 participants.

An economic evaluation of tofacitinib for the treatment of moderately-to-severely active ulcerative colitis: modeling the cost of treatment strategies in the United States.

To evaluate the cost differences between a treatment strategy including tofacitinib (TOFA) vs treatment strategies including adalimumab (ADA), golimumab (GOL), infliximab (IFX), and vedolizumab (VEDO) among all patients with moderate-to-severe ulcerative colitis (UC) (further stratified by patients naïve/exposed to tumor necrosis factor inhibitors [TNFis]). An Excel-based decision-analytic model was developed to evaluate costs from the perspective of a third-party US payer over 2 years. Efficacy and safety parameters were taken from prescribing information and published trials.

Comparing self-directed methods for training staff to create graphs using Graphpad Prism.

An important skill for behavior analysts is creating graphs that clearly convey outcomes and conform to publication conventions. GraphPad Prism is software designed for creating scientific graphs, but no prior research has empirically evaluated training graphing skills using Prism. Two effective training methods are enhanced written instructions (EWI) and video modeling with voiceover instructions (VMVO), but no single-subject studies have compared the effects of these methods.

Delayed Treatment Acceleration in Patients with Rheumatoid Arthritis Who Have Inadequate Response to Initial Tumor Necrosis Factor Inhibitors: Data from the Corrona Registry.

Background: The implementation of treat-to-target principles in rheumatoid arthritis (RA) has not been fully investigated in patients with inadequate response to tumor necrosis factor (TNF) inhibitor treatment.

Objectives: To evaluate the prevalence of an inadequate response to initial TNF inhibitor treatment at 6 and 12 months among patients with RA in a real-world patient registry, as well as the delay in therapy adjustment and its impact on disease activity and patient-reported outcome (PRO) measures.

Methods: This analysis is based on data of patients with moderate or severe disease activity (Clinical Disease Activity Index [CDAI] score >10) who were included in the Consortium of Rheumatology Researchers of North America (Corrona) RA registry, a prospective, observational database.

An Economic Evaluation of Tofacitinib Treatment in Rheumatoid Arthritis After Methotrexate or After 1 or 2 TNF Inhibitors from a U.S. Payer Perspective.

Background: Treatment cycling with biologic disease-modifying anti-rheumatic drugs, such as tumor necrosis factor inhibitors (TNFi), is common among patients with rheumatoid arthritis (RA) and can result in reduced clinical efficacy and increased economic burden. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA.

Objective: To evaluate and compare the economic effect of tofacitinib 5 mg twice daily (BID) treatment directly after methotrexate (MTX) in the MTX-inadequate responder population, or after MTX and 1 TNFi (adalimumab [ADA] or etanercept [ETN]) or 2 TNFi (ADA and ETN) in TNF-inadequate responder patients with RA, from a U.

The Challenge of Managing Psoriasis: Unmet Medical Needs and Stakeholder Perspectives.

Background: Psoriasis is a debilitating chronic inflammatory autoimmune disease affecting approximately 7.4 million adults in the United States. Plaque psoriasis is the most common form, affecting 80% to 90% of patients.

An Economic Evaluation of Tofacitinib Treatment in Rheumatoid Arthritis: Modeling the Cost of Treatment Strategies in the United States.

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib is approved in the United States for use in adults with moderately to severely active RA and an inadequate response or intolerance to methotrexate.

Objectives: To (a) evaluate, using an economic model, the treatment costs of an RA strategy including tofacitinib, compared with adalimumab, etanercept, certolizumab and tocilizumab biologic RA treatment strategies, which are commonly prescribed in the United States, and (b) assess the economic impact of monotherapy and combination therapy in patients who had an inadequate response to methotrexate therapy (MTX-IR analysis) and to combination therapy in patients who had an inadequate response to a tumor necrosis factor inhibitor (TNF-IR analysis).

Primary Nonadherence, Associated Clinical Outcomes, and Health Care Resource Use Among Patients with Rheumatoid Arthritis Prescribed Treatment with Injectable Biologic Disease-Modifying Antirheumatic Drugs.

Background: Adherence to biologic disease-modifying antirheumatic drugs (bDMARDs) among patients with rheumatoid arthritis (RA) is often suboptimal in routine clinical practice. Low or nonadherence can reduce the effectiveness of bDMARD therapies.

Objective: To evaluate filling of newly prescribed initial bDMARDs for the treatment of RA and evaluate potential for characterizing treatment decisions and patient outcomes.

Shaking the Tree: Multi-locus Sequence Typing Usurps Current Onchocercid (Filarial Nematode) Phylogeny.

During the past twenty years, a number of molecular analyses have been performed to determine the evolutionary relationships of Onchocercidae, a family of filarial nematodes encompassing several species of medical or veterinary importance. However, opportunities for broad taxonomic sampling have been scarce, and analyses were based mainly on 12S rDNA and coxI gene sequences. While being suitable for species differentiation, these mitochondrial genes cannot be used to infer phylogenetic hypotheses at higher taxonomic levels.

Real-world evaluation of TNF-inhibitor utilization in rheumatoid arthritis.

Objectives: To evaluate 12-month treatment patterns, healthcare resource use (HCRU), and costs for patients with rheumatoid arthritis (RA), following initiation of index TNF inhibitors (TNFi) and subsequent biologic DMARDs (bDMARDs).

Methods: This was a retrospective cohort analysis of adults with RA newly initiating TNFi in the Truven Marketscan Commercial Claims and Encounters and Medicare Supplemental Databases during 2010-2013. A sub-group of patients who switched to a bDMARD within 12 months post-index and within 180 days of last index TNFi were subsequently evaluated over 12 months.

An evaluation of response prompts for teaching behavior chains.

Individuals who have been diagnosed with autism spectrum disorders can have difficulty acquiring new skills, and teaching procedures found to be efficient with 1 individual may not be efficient with others. However, relatively little research has evaluated methods to identify efficient, individualized response-prompt and prompt-fading procedures. We evaluated an assessment of multiple response prompts and prompt-fading procedures with 10 individuals with an autism spectrum disorder.

Effects of data sampling on graphical depictions of learning.

Continuous and discontinuous data-collection methods were compared in the context of discrete-trial programming. Archival data sets were analyzed using trial sampling (1st 5 trials, 1st 3 trials, and 1st trial only) and session sampling (every other session, every 3rd session, and every 5th session). Results showed that trial sampling systematically underestimated the number of sessions and days to mastery and overestimated the number of sessions and days to the 1st independent response.

Implementing high-temperature short-time media treatment in commercial-scale cell culture manufacturing processes.

The production of therapeutic proteins by mammalian cell culture is complex and sets high requirements for process, facility, and equipment design, as well as rigorous regulatory and quality standards. One particular point of concern and significant risk to supply chain is the susceptibility to contamination such as bacteria, fungi, mycoplasma, and viruses. Several technologies have been developed to create barriers for these agents to enter the process, e.

Online interactive tutorials for creating graphs with excel 2007 or 2010.

Graphic display of clinical data is a useful tool for the behavior-analytic clinician. However, graphs can sometimes be difficult to create. We describe how to access and use an online interactive tutorial that teaches the user to create a variety of graphs often used by behavior analysts.

Elimination of position-biased responding in individuals with autism and intellectual disabilities.

Five individuals with autism or other developmental disabilities participated in paired-stimulus preference assessments during repeated baseline probes. All subjects initially showed a pronounced bias by typically selecting the stimulus placed in either the left or right position. Biased responding for 3 subjects was eliminated when training trials were conducted in which a stimulus of known lesser quality was presented as one of the choices.

Single pass tangential flow filtration to debottleneck downstream processing for therapeutic antibody production.

As the therapeutic monoclonal antibody (mAb) market continues to grow, optimizing production processes is becoming more critical in improving efficiencies and reducing cost-of-goods in large-scale production. With the recent trends of increasing cell culture titers from upstream process improvements, downstream capacity has become the bottleneck in many existing manufacturing facilities. Single Pass Tangential Flow Filtration (SPTFF) is an emerging technology, which is potentially useful in debottlenecking downstream capacity, especially when the pool tank size is a limiting factor.