Generating and validating renewable affimer protein binding reagents targeting SH2 domains.

Despite SH2 domains, being pivotal in protein interactions linked to various diseases like cancer, we lack specific research tools for intracellular assays. Understanding SH2-mediated interactions and creating effective inhibitors requires tools which target individual protein domains. Affimer reagents exhibit promise, yet their potential against the extensive SH2 domain family remains largely unexplored.

Frequency of supervised consumption service use and acute care utilization in people who inject drugs.

Background: Supervised consumption service (SCS) use among people who inject drugs may reduce acute care utilization; however, prior studies have been limited by self-reported outcomes and dichotomous exposures.

Methods: We conducted a prospective cohort study using linked questionnaire and health administrative data among people who inject drugs in Toronto, Canada (2018-2020). Baseline SCS use frequency was defined by a participant's self-reported proportion of injections performed at an SCS over the past six months: "all/most" (≥75 %), "some" (26-74 %), "few" (1-25 %), or "none" (0 %).

Proteomics of brain, CSF, and plasma identifies molecular signatures for distinguishing sporadic and genetic Alzheimer's disease.

Proteomic studies for Alzheimer's disease (AD) are instrumental in identifying AD pathways but often focus on single tissues and sporadic AD cases. Here, we present a proteomic study analyzing 1305 proteins in brain tissue, cerebrospinal fluid (CSF), and plasma from patients with sporadic AD, risk variant carriers, patients with autosomal dominant AD (ADAD), and healthy individuals. We identified 8 brain, 40 CSF, and 9 plasma proteins that were altered in individuals with sporadic AD, and we replicated these findings in several external datasets.

Gaseous nitric oxide tumor ablation induces an anti-tumor abscopal effect.

Background: In-situ tumor ablation provides the immune system with the appropriate antigens to induce anti-tumor immunity. Here, we present an innovative technique for generating anti-tumor immunity by delivering exogenous ultra-high concentration (> 10,000 ppm) gaseous nitric oxide (UHCgNO) intratumorally.

Methods: The capability of UHCgNO to induce apoptosis was tested in vitro in mouse colon (CT26), breast (4T1) and Lewis lung carcinoma (LLC-1) cancer cell lines.

Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined.

COVID-19 Outbreak Associated with a SARS-CoV-2 R.1 Lineage Variant in a Skilled Nursing Facility After Vaccination Program - Kentucky, March 2021.

Although COVID-19 mRNA vaccines demonstrated high efficacy in clinical trials (1), they were not 100% efficacious. Thus, some infections postvaccination are expected. Limited data are available on effectiveness in skilled nursing facilities (SNFs) and against emerging variants.

Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts.

Objective: We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients.

Design: The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites.

The correlation between vitamin D levels and demographics in patients with gastrointestinal disorders; a cross-sectional study.

Aim: The aim of the present study was to evaluate vitamin D levels, in correlation with age, body mass index (BMI), gender and ethnicity, in patients with gastrointestinal disorders (GID).

Background: Vitamin D deficiency (VDD) is a global health issue, affecting over 1 billion people. A great body of evidence has shown that it can lead to increased morbidity and mortality.

Predictors of radiation necrosis in long-term survivors after Gamma Knife stereotactic radiosurgery for brain metastases.

Background: The long-term risk of necrosis after radiosurgery for brain metastases is uncertain. We aimed to investigate incidence and predictors of radiation necrosis for individuals with more than 1 year of survival after radiosurgery for brain metastases.

Methods: Patients who had a diagnosis of brain metastases treated between December 2006 and December 2014, who had at least 1 year of survival after first radiosurgery were retrospectively reviewed.

Maternal B12, Folate and Homocysteine Concentrations and Offspring Cortisol and Cardiovascular Responses to Stress.

Context: Imbalances in maternal 1-carbon nutrients (vitamin B12, folate) have been shown to be associated with higher offspring cardiometabolic risk markers in India.

Objective: We examined the hypothesis that low plasma vitamin B12 (B12) and high folate and homocysteine concentrations in the mother are associated with higher hypothalamic-pituitary-adrenal axis (cortisol) and cardiovascular responses during the Trier Social Stress Test for Children (TSST-C) in an Indian birth cohort.

Methods: Adolescents (n = 264; mean age: 13.

Full noncontact laser ultrasound: first human data.

Full noncontact laser ultrasound (LUS) imaging has several distinct advantages over current medical ultrasound (US) technologies: elimination of the coupling mediums (gel/water), operator-independent image quality, improved repeatability, and volumetric imaging. Current light-based ultrasound utilizing tissue-penetrating photoacoustics (PA) generally uses traditional piezoelectric transducers in contact with the imaged tissue or carries an optical fiber detector close to the imaging site. Unlike PA, the LUS design presented here minimizes the optical penetration and specifically restricts optical-to-acoustic energy transduction at the tissue surface, maximizing the generated acoustic source amplitude.

Affimers as anti-idiotypic affinity reagents for pharmacokinetic analysis of biotherapeutics.

Therapeutic antibodies are the fastest growing class of drugs in the treatment of cancer, and autoimmune and inflammatory diseases that require the concomitant development of assays to monitor therapeutic antibody levels. Here, we demonstrate that the use of Affimer nonantibody binding proteins provides an advantage over current antibody-based detection systems. For four therapeutic antibodies, we used phage display to isolate highly specific anti-idiotypic Affimer reagents, which selectively bind to the therapeutic antibody idiotype.

Affimer-Enzyme-Inhibitor Switch Sensor for Rapid Wash-free Assays of Multimeric Proteins.

Robust technology is required to underpin rapid point-of-care and in-field diagnostics to improve timely decision making across broad sectors. An attractive strategy combines target recognition and signal generating elements into an "active" enzyme-switch that directly transduces target-binding into a signal. However, approaches that are broadly applicable to diverse targets remain elusive.

Desmetramadol Has the Safety and Analgesic Profile of Tramadol Without Its Metabolic Liabilities: Consecutive Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Trials.

Desmetramadol is an investigational analgesic consisting of (+) and (-) enantiomers of the tramadol metabolite O-desmethyltramadol (M1). Tramadol is racemic and exerts analgesia by monoaminergic effects of (-)-tramadol and (-)-M1, and by the opioid (+)-M1. Tramadol labeling indicates cytochrome P450 (CYP) isozyme 2D6 ultrarapid metabolizer can produce dangerous (+)-M1 levels, and CYP2D6 poor metabolizers insufficient (+)-M1 for analgesia.

Economic assessment of patient navigation to colonoscopy-based colorectal cancer screening in the real-world setting at the University of Chicago Medical Center.

Background: This report details the cost effectiveness of a non-nurse patient navigation (PN) program that was implemented at the University of Chicago Medical Center to increase colonoscopy-based colorectal cancer (CRC) screening.

Methods: The authors investigated the impact of the PN intervention by collecting process measures. Individuals who received navigation were compared with a historic cohort of non-navigated patients.

Optimal Emotional Profiles for Peak Performance in Strength and Conditioning.

Cooper, JJ, Johnson, M, Radcliffe, J, and Fisher, J. Optimal emotional profiles for peak performance in strength and conditioning. J Strength Cond Res 35(3): 833-840, 2021-This study investigated athletes' performance-related emotions and emotional profiles for optimal performance in strength and conditioning (S&C).

Improving Value of Care for Older Adults With Advanced Medical Illness and Functional Decline: Cost Analyses of a Home-Based Palliative Care Program.

Context: Identifying high-value health care delivery for patients with clinically complex and high-cost conditions is important for future reimbursement models.

Objectives: The objective of this study was to assess the Medicare reimbursement savings of an established palliative care homebound program.

Methods: This is a retrospective cohort study involving 50 participants enrolled in a palliative care homebound program and 95 propensity-matched control patients at Mayo Clinic in Rochester, Minnesota, between September 1, 2012, and March 31, 2013.

Large-Scale Variability of Inpatient Tacrolimus Therapeutic Drug Monitoring at an Academic Transplant Center: A Retrospective Study.

Background: Inpatient tacrolimus therapeutic drug monitoring (TDM) lacks standardized guidelines. In this study, the authors analyzed variability in the preanalytical phase of the inpatient tacrolimus TDM process at their institution.

Methods: Patients receiving tacrolimus (twice-daily formulation) and tacrolimus laboratory analysis were included in the study.

ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation.

Objectives: Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive 'normal' IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens.

Design: The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015.

Gluten-Free Diet Indications, Safety, Quality, Labels, and Challenges.

A gluten-free diet (GFD) is the safest treatment modality in patient with coeliac disease (CD) and other gluten-related disorders. Contamination and diet compliance are important factors behind persistent symptoms in patients with gluten related-disorders, in particular CD. How much gluten can be tolerated, how safe are the current gluten-free (GF) products, what are the benefits and side effects of GFD? Recent studies published in on gluten-free products' quality, availability, safety, as well as challenges related to a GFD are discussed.

Affimer proteins are versatile and renewable affinity reagents.

Molecular recognition reagents are key tools for understanding biological processes and are used universally by scientists to study protein expression, localisation and interactions. Antibodies remain the most widely used of such reagents and many show excellent performance, although some are poorly characterised or have stability or batch variability issues, supporting the use of alternative binding proteins as complementary reagents for many applications. Here we report on the use of Affimer proteins as research reagents.

Multispecialty Rating of Evidence-Based Conditions for Intravenous Immunoglobulin Therapy Using a 3-Axis Prioritization Algorithm.

Background: A 3-axis prioritization algorithm was proposed and was evaluated in a US multispecialist pilot study to obtain uniform consensus regarding effective practices for the use of intravenous immunoglobulin (IVIG) therapy.

Objective: The primary objective was to use consensus-building methodologies to rate disease states for IVIG utilization while considering disease severity and the efficacy of alternative therapeutic options to IVIG from the perspective of US multispecialists.

Methods: A 7-member multispecialty physician expert panel was surveyed to rate 50 disease states and to determine their level of agreement with the American Academy of Allergy, Asthma & Immunology (AAAAI) evidence-based medicine (EBM) ratings.

An economic evaluation of the costs of training a medical scribe to work in Emergency Medicine.

Objective: To undertake a cost analysis of training medical scribes in an ED.

Methods: This was a pilot, observational, single-centre study at Cabrini ED, Melbourne, Australia, studying the costs of initiating a scribe programme from the perspective of the hospital and Australian Health sector. Recruitment and training occurred between August 2015 and February 2016 and comprised of a prework course (1 month), prework training sessions and clinical training shifts for scribe trainees (2-4 months, one shift per week) who were trained by emergency physicians.