Mammalian cell-based production of glycans, glycopeptides and glycomodules.

Access to defined glycans and glycoconjugates is pivotal for discovery, dissection, and harnessing of a range of biological functions orchestrated by cellular glycosylation processes and the glycome. We previously employed genetic glycoengineering by nuclease-based gene editing to develop sustainable production of designer glycoprotein therapeutics and cell-based glycan arrays that display glycans in their natural context at the cell surface. However, access to human glycans in formats and quantities that allow structural studies of molecular interactions and use of glycans in biomedical applications currently rely on chemical and chemoenzymatic syntheses associated with considerable labor, waste, and costs.

Higher fibre and lower carbohydrate intake are associated with favourable CGM metrics in a cross-sectional cohort of 470 individuals with type 1 diabetes.

Aims/hypothesis: The aim of this work was to investigate the association between macronutrient intakes and continuous glucose monitoring (CGM) metrics in individuals with type 1 diabetes.

Methods: In 470 individuals with type 1 diabetes of the GUTDM1 cohort (65% female, median age 40 [IQR 28-53] years, median diabetes duration 15 [IQR 6-29] years), we used logistic regression to establish associations between macronutrient intakes and the CGM metrics time in range (TIR, time spent between 3.9-10.

Can fecal microbiota transplantations modulate autoimmune responses in type 1 diabetes?

Type 1 diabetes (T1D) is a chronic autoimmune disease targeting insulin-producing pancreatic beta cells. T1D is a multifactorial disease incorporating genetic and environmental factors. In recent years, the advances in high-throughput sequencing have allowed researchers to elucidate the changes in the gut microbiota taxonomy and functional capacity that accompany T1D development.

Optical coherence tomography as a prognostic tool for disability progression in MS: a systematic review.

Since multiple sclerosis (MS) is characterized by an unpredictable disease course, accurate prognosis and personalized treatment constitute an important challenge in clinical practice. We performed a qualitative systematic review to assess the predictive value of retinal layer measurement by spectral-domain optical coherence tomography (SD-OCT) in MS patients. Longitudinal MS cohort studies that determined the risk of clinical deterioration based on peripapillary retinal nerve fiber layer (pRNFL) and/or macular ganglion cell-inner plexiform layer (mGCIPL) atrophy were included.

Intralipid administration in case of a severe venlafaxine overdose in a patient with previous gastric bypass surgery.

This case describes a patient with a history of bariatric surgery who was admitted to our hospital with a severe venlafaxine intoxication. Due to the altered anatomy of the gastrointestinal tract, the use of oral activated charcoal and large volumes of laxatives to prevent further uptake of venlafaxine was hampered. This resulted in massive absorption and a severe serotonergic syndrome.

Comparison between EQ-5D-5L and PROMIS-10 to evaluate health-related quality of life 3 months after stroke: a cross-sectional multicenter study.

Background: Although the use of patient-reported outcome measures to assess Health-Related Quality of Life (HRQoL) has been advocated, it is still open to debate which patient-reported outcome measure should be preferred to evaluate HRQoL after stroke.

Aim: To compare the measurement properties (including concurrent validity and discriminant ability) between the 5-dimensional 5-level EuroQol (EQ-5D-5L) and the Patient-Reported Outcomes Measurement Information System 10-Question Global Health Short Form (PROMIS-10) to evaluate HRQoL 3 months after stroke.

Design: Cross-sectional study.

Predictors of mentoring relationship quality: Investigation from the perspectives of youth and parent participants in Big Brothers Big Sisters of Canada one-to-one mentoring programs.

Aims: This study examined predictors of mentoring relationship quality (MRQ) as reported by youth and parents participating in Big Brothers Big Sisters (BBBS) of Canada one-to-one mentoring programs.

Methods: Mentoring program capacity and other external supports, youth personal and environmental risk, youth and parent attitudes and motives, and mentoring relationship processes and attributes were examined as predictors of MRQ at 18 months following youth referral to the program using data from a longitudinal study of the Canadian BBBS mentoring programs.

Results: For youth (n = 335), significant predictors of MRQ included: minimal difficulties pairing youth and mentors, perceptions of shared attributes with their mentor, mentor emotional engagement and support, and longer relationships.

How Mentor Support Interacts With Mother and Teacher Support in Predicting Youth Academic Adjustment: An Investigation Among Youth Exposed to Big Brothers Big Sisters of Canada Programs.

This study examines three potential contributions (i.e., additive only, hierarchical compensatory, and hierarchical conditional) of mentor support to youth academic adjustment, taking into account interactions with support from mothers and teachers.

Appropriate Use of Venous Imaging and Analysis of the D-Dimer/Clinical Probability Testing Paradigm in the Diagnosis and Location of Deep Venous Thrombosis.

Background: The D-dimer (DD) level combined with the pretest Wells criteria probability (WCP) score can safely exclude deep venous thrombosis (DVT). The objective of this study was to examine the correlation between DD results alongside WCP score with findings on venous duplex ultrasound (VDU). The hypothesis is that VDU remains overutilized in low-risk patients with negative DD and that higher DD levels may correlate with thrombus burden and location.

Hyperaemic microvascular resistance predicts clinical outcome and microvascular injury after myocardial infarction.

Objectives: Early detection of microvascular dysfunction after acute myocardial infarction (AMI) could identify patients at high risk of adverse clinical outcome, who may benefit from adjunctive treatment. Our objective was to compare invasively measured coronary flow reserve (CFR) and hyperaemic microvascular resistance (HMR) for their predictive power of long-term clinical outcome and cardiac magnetic resonance (CMR)-defined microvascular injury (MVI).

Methods: Simultaneous intracoronary Doppler flow velocity and pressure measurements acquired immediately after revascularisation for AMI from five centres were pooled.

Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21.

The adjuvant properties of the saponin QS-21 have been known for decades. It is a component of the Adjuvant System AS01 that is used in several vaccine candidates. QS-21 strongly potentiates both cellular and humoral immune responses to purified antigens, yet how it activates immune cells is largely unknown.

Everolimus in Patients With Advanced Follicular-Derived Thyroid Cancer: Results of a Phase II Clinical Trial.

Background: Mammalian target of rapamycin (mTOR) upregulation has been reported to be involved in the pathogenesis of thyroid tumors, and treatment with the mTOR inhibitor everolimus has shown promising results in endocrine tumors. We conducted a prospective phase II clinical trial to determine the efficacy and safety of everolimus in patients with advanced follicular-derived thyroid cancer.

Patients And Methods: Twenty-eight patients with progressive metastatic or locally advanced radioactive refractory differentiated thyroid cancer and 7 patients with anaplastic thyroid cancer were included and received everolimus 10 mg orally once daily.

A Semi-Physiological Population Model to Quantify the Effect of Hematocrit on Everolimus Pharmacokinetics and Pharmacodynamics in Cancer Patients.

Introduction And Objective: Everolimus (a drug from the class of mammalian target of rapamycin [mTOR] inhibitors) is associated with frequent toxicity-related dose reductions. Everolimus accumulates in erythrocytes, but the extent to which hematocrit affects everolimus plasma pharmacokinetics and pharmacodynamics is unknown. We aimed to investigate the everolimus pharmacokinetics/pharmacodynamics and the influence of hematocrit in cancer patients.

Everolimus pharmacokinetics and its exposure-toxicity relationship in patients with thyroid cancer.

Background: Everolimus is a mTOR inhibitor used for the treatment of different solid malignancies. Many patients treated with the registered fixed 10 mg dose once daily are in need of dose interruptions, reductions or treatment discontinuation due to severe adverse events. This study determined the correlation between systemic everolimus exposure and toxicity.

Examining the validity of the adapted Alabama Parenting Questionnaire-Parent Global Report Version.

The purpose of the present study was to comprehensively examine the validity of an adapted version of the parent global report form of the Alabama Parenting Questionnaire (APQ) with respect to its factor structure, relationships with demographic and response style covariates, and differential item functioning (DIF). The APQ was adapted by omitting the corporal punishment and the other discipline items. The sample consisted of 674 Canadian and United States families having a 9- to 12-year-old child and at least 1 parent figure who had received treatment within the past 5 years for alcohol problems or met criteria for alcohol abuse or dependence.

Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial.

Objective. Until recently, advanced medullary thyroid cancer (MTC) had few treatment options except surgery. The mTOR inhibitor everolimus has shown encouraging results in neuroendocrine tumors.

Effect of position of near addition in an asymmetric refractive multifocal intraocular lens on quality of vision.

Purpose: To evaluate the impact of the position of an asymmetric multifocal near segment on visual quality.

Setting: Cathedral Eye Clinic, Belfast, United Kingdom.

Design: Retrospective comparative case series.

Dried blood spot analysis for therapeutic drug monitoring of pazopanib.

Dried blood spot (DBS) sampling is potentially a more patient-friendly and flexible alternative to venous sampling of pazopanib. This study determined the agreement between pazopanib DBS and plasma concentrations to facilitate implementation of pazopanib DBS sampling into clinical practice. Paired DBS and plasma samples were collected in 12 patients.

Integrated semi-physiological pharmacokinetic model for both sunitinib and its active metabolite SU12662.

Aims: Previously published pharmacokinetic (PK) models for sunitinib and its active metabolite SU12662 were based on a limited dataset or lacked important elements such as correlations between sunitinib and its metabolite. The current study aimed to develop an improved PK model that circumvented these limitations and to prove the utility of the PK model in treatment optimization in clinical practice.

Methods: One thousand two hundred and five plasma samples from 70 cancer patients were collected from three PK studies with sunitinib and SU12662.

Therapeutic drug monitoring to individualize the dosing of pazopanib: a pharmacokinetic feasibility study.

Background: Patients treated with the standard dose of pazopanib show a large interpatient variability in drug exposure defined as the area under the plasma concentration-time curve (AUC0-24h). The primary objective of this study was to evaluate the feasibility of pharmacokinetics (PK)-guided individualized dosing to reduce the interpatient variability in pazopanib exposure.

Methods: Thirteen patients were treated with pazopanib for 3 consecutive periods of 2 weeks.

Individualized dosing of tyrosine kinase inhibitors: are we there yet?

Tyrosine kinase inhibitors (TKIs) are registered at a fixed oral dose, despite their large variability in pharmacokinetics (PK). Given that the evidence for a relation between drug exposure and treatment outcome is growing, this one-dose-fits-all approach can unintentionally lead to under- and overexposure. Dose individualization could lower this variability and thereby beneficially effect treatment outcome.

Effect of gastrointestinal resection on sunitinib exposure in patients with GIST.

Background: GIST patients often undergo GI-surgery. Previous studies have shown that imatinib and nilotinib exposures were decreased in GIST patients with prior major gastrectomy. We investigated whether major gastrectomy influences the exposure to sunitinib and its active metabolite SU12662.