Application of experimental design methodologies in the enantioseparation of pharmaceuticals by capillary electrophoresis: a review

Chirality is one of the major issues in pharmaceutical research and industry. Capillary electrophoresis (CE) is an interesting alternative to the more frequently used chromatographic techniques in the enantioseparation of pharmaceuticals, and is used for the determination of enantiomeric ratio, enantiomeric purity, and in pharmacokinetic studies. Traditionally, optimization of CE methods is performed using a univariate one factor at a time (OFAT) approach; however, this strategy does not allow for the evaluation of interactions between experimental factors, which may result in ineffective method development and optimization. In the last two decades, Design of Experiments (DoE) has been frequently employed to better understand the multidimensional effects and interactions of the input factors on the output responses of analytical CE methods. DoE can be divided into two types: screening and optimization designs. Furthermore, using Quality by Design (QbD) methodology to develop CE-based enantioselective techniques is becoming increasingly popular. The review presents the current use of DoE methodologies in CE-based enantioresolution method development and provides an overview of DoE applications in the optimization and validation of CE enantioselective procedures in the last 25 years. Moreover, a critical perspective on how different DoE strategies can aid in the optimization of enantioseparation procedures is presented

New Trends in the Quality Control of Enantiomeric Drugs: Quality by Design-Compliant Development of Chiral Capillary Electrophoresis Methods

Capillary electrophoresis (CE) is a potent method for analyzing chiral substances and is commonly used in the enantioseparation and chiral purity control of pharmaceuticals from different matrices. The adoption of Quality by Design (QbD) concepts in analytical method development, optimization and validation is a widespread trend observed in various analytical approaches including chiral CE. The application of Analytical QbD (AQbD) leads to the development of analytical methods based on sound science combined with risk management, and to a well understood process clarifying the influence of method parameters on the analytical output. The Design of Experiments (DoE) method employing chemometric tools is an essential part of QbD-based method development, allowing for the simultaneous evaluation of experimental parameters as well as their interaction. In 2022 the International Council for Harmonization (ICH) released two draft guidelines (ICH Q14 and ICH Q2(R2)) that are intended to encourage more robust analytical procedures. The ICH Q14 guideline intends to harmonize the scientific approaches for analytical procedures’ development, while the Q2(R2) document covers the validation principles for the use of analytical procedures including the recent applications that require multivariate statistical analyses. The aim of this review is to provide an overview of the new prospects for chiral CE method development applied for the enantiomeric purity control of pharmaceuticals using AQbD principles. The review also provides an overview of recent research (2012–2022) on the applicability of CE methods in chiral drug impurity profiling

Choosing the nutritional intervention to overweight and obese patients

Weight problems occur in 1.5 billion people and these are a risk factor for type 2 diabetes, cardiovascular, pulmonary and periodontal diseases, cancer and osteoporosis. Our study aimed to evaluate the caloric intake, vitamins and minerals from food before a nutritional intervention to overweight and obese patients

Choosing the nutritional intervention to overweight and obese patients

Weight problems occur in 1.5 billion people and these are a risk factor for type 2 diabetes, cardiovascular, pulmonary and periodontal diseases, cancer and osteoporosis. Our study aimed to evaluate the caloric intake, vitamins and minerals from food before a nutritional intervention to overweight and obese patients

Acute cerebral MCA ischemia with secondary severe head injury and acute intracerebral and subdural haematoma: Case report

Generally, according to international literature, cerebral ischemia is a secondary posttraumatic lesion produced by direct compression in the context of a cerebral herniation syndrome or indirect by vasospasm produced by posttraumatic subarachnoid, subdural or intraventricular hemorrhages. We present the case of a patient with an acute MCA ischemia with severe head injury due to a fall with subsequent intracranial acute intracerebral and subdural hematoma which evolved with acute left uncal, parahipocampal and subfalcinecerebral herniation (coma, GCS 6, left mydriasis, right severe hemiparesis). Surgical emergency aspiration of the hematomas was performed. Postoperative treatment of cerebral ischemia and residual hematomas was properly done. We consider important and underdiagnosed the association of cerebral ischemia and secondary posttraumatic brain injuries. Abbreviations: MCA-middle cerebral artery, GCS- Glasgow Coma Scale, ICA-internal carotid artery, PCA-posterior cerebral artery, ACA-anterior cerebral artery. Conclusion: We present a case of a patient with an acute MCA ischemia with secondary head injury due to a fall with subsequent intracranial acute intracerebral and subdural hematomas. Surgical emergency aspiration of the hematomas was performed. The treatment was performed for both lesions (cerebral ischemia and posttraumatic hematomas) with vitamins B, neurotrophycs, pain killers, antibiotics. Unfortunately, due to aggravation of the Mendelson syndrome, the patient died 7 days later

Multifaceted determinants for achieving glycemic control the international diabetes management practice study (IDMPS)

OBJECTIVE - The International Diabetes Mellitus Practice Study is a 5-year survey documenting changes in diabetes treatment practice in developing regions. RESEARCH DESIGN AND METHODS - Logistic regression analysis was used to identify factors for achieving A1C <7% in 11,799 patients (1,898 type 1 diabetic and 9,901 type 2 diabetic) recruited by 937 physicians from 17 countries in Eastern Europe (n = 3,519), Asia (n = 5,888), Latin America (n = 2,116), and Africa (n = 276). RESULTS - Twenty-two percent of type 1 diabetic and 36% of type 2 diabetic patients never had A1C measurements. In those with values for A1C, blood pressure, and LDL cholesterol, 7.5% of type 1 diabetic (n = 696) and 3.6% of type 2 diabetic (n = 3,896) patients attained all three recommended targets (blood pressure < 130/80 mmHg, LDL cholesterol <100 mg/dl, and A1C <7%). Self-monitoring of blood glucose was the only predictor for achieving the A1C goal in type 1 diabetes (odds ratios: Asia 2.24, Latin America 3.55, and Eastern Europe 2.42). In type 2 diabetes, short disease duration (Asia 0.97, Latin America 0.97, and Eastern Europe 0.82) and treatment with few oral glucose-lowering drugs (Asia 0.64, Latin America 0.76, and Eastern Europe 0.62) were predictors. Other region-specific factors included lack of microvascular complications and old age in Latin America and Asia; health insurance coverage and specialist care in Latin America; lack of obesity and self-adjustment of insulin dosages in Asia; and training by a diabetes educator, self-monitoring of blood glucose in patients who self-adjusted insulin, and lack of macrovascular complications in Eastern Europe. CONCLUSIONS - In developing countries, factors pertinent to patients, doctors, and health care systems all impact on glycemic control.Facultad de Ciencias Médica

Silicon Mie Resonators for Highly Directional Light Emission from monolayer MoS2

Controlling light emission from quantum emitters has important applications ranging from solid-state lighting and displays to nanoscale single-photon sources. Optical antennas have emerged as promising tools to achieve such control right at the location of the emitter, without the need for bulky, external optics. Semiconductor nanoantennas are particularly practical for this purpose because simple geometries, such as wires and spheres, support multiple, degenerate optical resonances. Here, we start by modifying Mie scattering theory developed for plane wave illumination to describe scattering of dipole emission. We then use this theory and experiments to demonstrate several pathways to achieve control over the directionality, polarization state, and spectral emission that rely on a coherent coupling of an emitting dipole to optical resonances of a Si nanowire. A forward-to-backward ratio of 20 was demonstrated for the electric dipole emission at 680 nm from a monolayer MoS2 by optically coupling it to a Si nanowire

Glutamatergic correlates of gamma-band oscillatory activity during cognition: a concurrent ER-MRS and EEG study

Frequency specific synchronisation of neuronal firing within the gamma-band (30-70 Hz) appears to be a fundamental correlate of both basic sensory and higher cognitive processing. In-vitro studies suggest that the neurochemical basis of gamma-band oscillatory activity is based on interactions between excitatory (i.e. glutamate) and inhibitory (i.e. GABA) neurotransmitter concentrations. However, the nature of the relationship between excitatory neurotransmitter concentration and changes in gamma band activity in humans remains undetermined. Here, we examine the links between dynamic glutamate concentration and the formation of functional gamma-band oscillatory networks. Using concurrently acquired event-related magnetic resonance spectroscopy and electroencephalography, during a repetition-priming paradigm, we demonstrate an interaction between stimulus type (object vs. abstract pictures) and repetition in evoked gamma-band oscillatory activity, and find that glutamate levels within the lateral occipital cortex, differ in response to these distinct stimulus categories. Importantly, we show that dynamic glutamate levels are related to the amplitude of stimulus evoked gamma-band (but not to beta, alpha or theta or ERP) activity. These results highlight the specific connection between excitatory neurotransmitter concentration and amplitude of oscillatory response, providing a novel insight into the relationship between the neurochemical and neurophysiological processes underlying cognition