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关键词： clinical trial   C-peptide   hypoglycaemia   insulin glargine   insulin initiation   type 2 diabetes mellitus  

摘要： Patient characteristics associated with hypoglycaemia frequency during insulin glargine 100 U/mL (Gla-100) titration and clinical outcomes at Week 24 were examined using participant-level data from 16 treat-to-target trials involving individuals with type 2 diabetes mellitus who were inadequately controlled with oral antidiabetes drugs and were initiating Gla-100 (n = 3549). Hypoglycaemia (plasma glucose <3.9 mmol/L or severe) during the first 8 weeks of titration was stratified by number of events (0, 1-3 and >= 4), resulting in 72.5%, 20.6% and 6.9% of participants in each group, respectively. Changes in glycaemia, body weight and insulin dose from baseline to Weeks 12 and 24 were analysed. Hypoglycaemia was more common in participants with lower BMI and fasting C-peptide, and in those undergoing sulfonylurea treatment. Glycaemic outcomes at Week 24 were similar in each hypoglycaemia group, despite the fact that the Week 24 mean daily dose and dose increase for Gla-100 were highest in participants without hypoglycaemia and were lowest in those experiencing >= 4 events. The risk of hypoglycaemia during Gla-100 titration depends mainly on patient characteristics and on sulfonylurea use and may delay dose titration, which apparently has little effect on short-term glycaemic control in a clinical trial setting.

关键词： Botulinum neurotoxin type A   IncobotulinumtoxinA   Shoulder spasticity   Stroke  

摘要： 266

关键词： Biosorption   Potentiometric titration   Biomass   Surface modification   Biosorbent   Buffering capacity  

摘要： In the present study, the relationship between the amount of anionic or cationic binding sites and adsorption capacities of biosorbents is discussed through potentiometric titration and mathematical model equations (proton-binding models). The poly(acrylic) acid-modified biomass (PAAB) and polyethylenimine-modified biomass (PEIB) derived from raw biomass (RB) Corynebacterium glutamicum (C. glutamicum) were used as cationic and anionic binding site-enhanced biosorbents, respectively. To obtain the sorption capacities of biomasses for anionic and cationic pollutants, isotherm tests were carried out using Basic Blue 3 (BB3, at pH 9) and Reactive Red 4 (RR4, at pH 2) as model anionic and cationic pollutants, respectively. The maximum sorption capacity (q(m)) of PAAB was 1.28 times higher than RB for BB3. In the case of PEIB, the sorption capacity was found to be 3.27 times higher than RB for RR4. A quantitative information of functional groups could be estimated by the application of proton-binding models to potentiometric titration results. In addition, the buffering capacities of functional groups were obtained from the parameters of pK models. An increasing ratio of sorption capacities was similar to that of the buffering capacities of modified biosorbents obtained from all conditions of pK models. Therefore, the fact that the sorption capacity of modified biomass can be predicted by comparing it with the buffering capacity of biosorbents was confirmed.

摘要： 5065

摘要： The field of nanotoxicology has evolved rapidly in the past two decades. Starting from simple nanomaterials and established toxicity assays, researchers' foci have shifted towards understanding the mechanisms underlying nanotoxicity. Furthermore, an important goal has been linking nanomaterial properties to biological responses to build predictive models for safer nanomaterial design. Here, we provide our perspectives, as analytical chemists, on the analytical challenges in nanotoxicology as the field is entering its third decade. We have identified these challenges to include understanding causal relationships in mechanistic studies of nanotoxicity, overcoming nanomaterial interferences for accurate nanotoxicity assays, connecting nanoparticle interactions to cellular responses at the single-cell level, and making chemical measurements at the nano-bio interface in real-time and in situ.

关键词： Monomers   Raman spectroscopy   Toxins   Polymers   Titration  

摘要： In this work, isothermal titration calorimetry (ITC) is employed as an affinity agent screening method for the surface-enhanced Raman scattering (SERS) detection of aflatoxin B1 (AFB1). AFB1, a potent carcinogen produced by a fungus that infects crops, is an important target due to the monitoring required based on its FDA regulation. Polymer affinity agents, like those studied here, have the potential to enable separation and detection of relevant small molecules such as pesticides, drugs, and biological toxins, like AFB1, especially when paired with a vibrational spectroscopy technique such as SERS. Herein, seven homopolymers were synthesized to be evaluated as AFB1 affinity agents based on hypothetical hydrogen bonding interactions. Nitrogen-inclusive poly(N-(2-aminoethyl) methacrylamide) (pAEMA) polymers and their oxygen analogs, poly(2-hydroxyethyl methacrylate) (pHEMA) were evaluated. ITC was demonstrated as an effective method for rapid screening among the polymer affinity agents. Chain lengths between seven and 39 repeat units were synthesized to study length-based variance in affinity agent performance. An ITC method was optimized and used for the rapid screening of polymer affinity agents. The results were compared to those generated by SERS. Good agreement between the ITC results and follow-up SERS sensing experiments showcased ITC's screening potential for analytical applications such as separation and detection.