Contraceptive access and use among women with migratory experience living in high-income countries: a scoping review.

BACKGROUND: Women who have migrated often encounter difficulties in accessing healthcare and experience inequitable sexual and reproductive health outcomes in destination countries. These health inequities include contraceptive access and use. To better understand what influences contraceptive access and use, this scoping review set out to synthesize the evidence on contraceptive access and use and on associated interventions among women with migratory experience in high-income countries (HICs) in Europe, North America and Australasia. METHODS: The scientific databases PubMed, Web of Science and CINAHL were searched for peer-reviewed quantitative, qualitative and mixed method articles published between January 2000 and June 2023. Articles were included if they reported on studies exploring contraceptive use to prevent pregnancies among women of reproductive age with migratory experience living in HICs. Two researchers independently screened and extracted data from the articles. Findings were categorized by patient and health system level factors according to Levesque et al.'s framework of access to health care. RESULTS: A total of 68 articles were included, about half (n = 32) from North America. The articles focused on the individual level rather than the health system level, including aspects such as women's contraceptive knowledge, the influence of culture and religion on accessing and using contraception, partner involvement, and differing health insurance coverage. On the health system level, the articles highlighted lack of information on contraceptive services, cultural (in)adequacy of services and communication aspects, contraceptives' side effects, as well as geographic availability and cost of services. The review further identified three articles reporting on interventions related to contraceptive counselling. CONCLUSIONS: There is a lack of knowledge regarding how health systems impose obstacles to contraceptive services for women with migratory experience on an organizational level, as research has focused heavily on the individual level. This review's findings may serve as a foundation for further research and advances in policy and practice, specifically recommending early provision of health system related information and contraceptive education, engagement of male partners in contraceptive discourses, cultural competency training for healthcare professionals, and strengthening of interpretation services for contraceptive counselling.

Every breath you take: High concentration of breathable microplastics in indoor environments.

The widespread presence of microplastics (MPs) in the air and their potential impact on human health underscore the pressing need to develop robust methods for quantifying their presence, particularly in the breathable fraction (<5 µm). In this study, Raman micro-spectroscopy (µRaman) was employed to assess the concentration of indoor airborne MPs >1 µm in four indoor environments (a meeting room, a workshop, and two apartments) under different levels of human activity. The indoor airborne MP concentration spanned between 58 and 684 MPs per cubic meter (MP m-3) (median 212 MP m-3, MPs/non-plastic ratio 0-1.6%), depending not only on the type and level of human activity, but also on the surface area and air circulation of the investigated locations. Additionally, we assessed in the same environments the filtration performance of a type IIR surgical facemask, which could overall retain 85.4 ± 3.9% of the MPs. We furthermore estimated a human MP intake from indoor air of 3415 ± 2881 MPs day-1 (mostly poly-amide MPs), which could be decreased to 283 ± 317 MPs day-1 using the surgical facemask. However, for the breathable fraction of MPs (1-5 µm), the efficiency of the surgical mask was reduced to 57.6%.

Cascades of Parametric Instabilities in the Tokamak Plasma Edge during Electron Cyclotron Resonance Heating.

We report observations of nonlinear two-plasmon decay instabilities (TPDIs) of a high-power microwave beam, a process similar to half-harmonic generation in optics, during electron cyclotron resonance heating in a tokamak. TPDIs are found to occur regularly in the plasma edge due to wave trapping in density fluctuations for various confinement modes, and the frequencies of both observed daughter waves agree with modeling. Emissions from a cascade of subsequent decays, which indicate a generation of ion Bernstein waves, are correlated with fast-ion generation. This emphasizes the limitations of standard linear microwave propagation models and possibly paves the way for novel microwave applications in plasmas.

"What matters to you" on the day of surgery: Protocol for a mixed methods study.

BACKGROUND: The anticipation of anesthesia and surgery is the source of fear and anxiety in millions of patients worldwide. Although patients' fear and anxiety are recognized, more knowledge is needed to address patient responses and needs. Understanding the needs of the patients are important, and asking patients directly is the first step towards addressing these needs. This again might help reducing medications such as anesthetics and postoperative pain relief. The aim of this study protocol is to describe how we will investigate what matters to patients on the day of surgery, as well as their degree-of-worry and surgical fear. METHODS: Using a convergent mixed methods design with equal weighting of the qualitative and quantitative data strand we take advantage of the international "What Matters To You" Day on June 6, 2024 to conduct a flash mob study. We will approach perioperative departments around Denmark to participate and eligible patients arriving to the perioperative department for surgery will be invited to participate. Consenting patients are asked to complete a survey in three parts regarding (1) what matters to you, (2) degree-of-worry, and (3) surgical fear. We will use qualitative analysis for the first part and descriptive statistics for second and third parts. The data strands will be analyzed separately followed by integrated analysis and joint displays.

Disparities in alcohol- and substance-related hospitalizations and deaths across sexual orientations in Canada: a longitudinal study.

OBJECTIVES: We aim to quantify disparities in substance-related acute events (i.e. hospitalizations and deaths for substances, including alcohol, cannabis, opioids, narcotics, and/or illicit drugs) across sexual orientations based on health administrative data. STUDY DESIGN: This was a longitudinal analysis from six waves of the Canadian Community Health Survey (2009-2014) linked to hospitalization/mortality data in Ontario, Canada. METHODS: The study sample consisted of survey respondents aged ≥15 (weighted n = 15,406,000) who provided a valid response to the question about sexual orientation. The primary outcome was substance-related acute events, including hospitalizations and deaths due to alcohol, cannabis, opioids, narcotics, and/or illicit drugs. Disparities in substance-related acute events across sexual orientation and gender were examined using flexible parametric survival analysis. RESULTS: Bisexual women had hazard ratios of 2.46 (95% confidence interval: 1.46-4.15) for any substance-related acute event and 2.67 (95% confidence interval: 1.42-5.00) for non-alcohol substance acute events compared to heterosexual women. Lesbian women did not exhibit significant differences in acute event risk compared to heterosexual women. Gay and bisexual men demonstrated elevated but not statistically significant risks compared to heterosexual men. CONCLUSIONS: Bisexual women face higher risks of substance-related acute events, potentially due to self-medication of unique stressors brought on by discrimination and isolation. Enhanced education and training for healthcare professionals are essential to increase awareness and sensitivity toward the heightened substance use risk among lesbian, gay, and bisexual individuals. Targeted interventions aimed at reducing substance use problems among bisexual individuals warrant increased funding and research.

Second Data Release from the European Pulsar Timing Array: Challenging the Ultralight Dark Matter Paradigm.

Pulsar Timing Array experiments probe the presence of possible scalar or pseudoscalar ultralight dark matter particles through decade-long timing of an ensemble of galactic millisecond radio pulsars. With the second data release of the European Pulsar Timing Array, we focus on the most robust scenario, in which dark matter interacts only gravitationally with ordinary baryonic matter. Our results show that ultralight particles with masses 10^{-24.0} eV≲m≲10^{-23.3} eV cannot constitute 100% of the measured local dark matter density, but can have at most local density ρ≲0.3 GeV/cm^{3}.

It matters how we measure - Quantification of microplastics in drinking water by µFTIR and µRaman.

The water treatment for microplastics (MP) at a Danish groundwater-based waterworks was assessed by Fourier-Transform IR micro-spectroscopy (µFTIR) (nominal size limit 6.6 µm) and compared to results from Raman micro-spectroscopy (µRaman) (nominal size limit 1.0 µm) on the same sample set. The MP abundance at the waterworks' inlet and outlet was quantified as MP counts per cubic metre (N/m3) and estimated MP mass per cubic metre (µg/m3). The waterworks' MP removal efficiency was found to be higher when analysing by µFTIR (counts: 78.14 ± 49.70%, mass: 98.73 ± 11.10%) and less fluctuating than when using µRaman (counts: 43.2%, mass: 75.1%). However, both techniques pointed to a value of ∼80% for the counts' removal efficiency of MPs >6.6 µm. Contrarily to what was shown by µRaman, no systematic leaking of MPs from the plastic elements of the facility could be identified for the µFTIR dataset, either from the counts (inlet 31.86 ± 17.17 N/m3, outlet 4.98 ± 2.09 N/m3) or mass estimate (inlet 76.30 ± 106.30 µg/m3, outlet 2.81 ± 2.78 µg/m3). The estimation of human MP intake from drinking water calculated from the µFTIR data (5 N/(year·capita)) proved to be approximately 332 times lower than that calculated from the µRaman dataset, although in line with previous studies employing µFTIR. By merging the MP length datasets from the two techniques, it could be shown that false negatives became prevalent in the µFTIR dataset already below 50 µm. Further, by fitting the overall frequency of the MP length ranges with a power function, it could be shown that µFTIR missed approximately 95.7% of the extrapolated MP population (1-1865.9 µm). Consequently, relying on only µFTIR may have led to underestimating the MP content of the investigated drinking water, as most of the 1-50 µm MP would have been missed.

Early referral of patients with suspected polymyalgia rheumatica - A systematic review.

INTRODUCTION: Prompt diagnosis and treatment of polymyalgia rheumatica (PMR) is crucial to prevent long-term complications and improve patient outcomes. However, there is currently no standardized approach to referral of suspected PMR patients to rheumatologists, leading to inconsistent management practices. The objective of this systematic review was to clarify the existing evidence regarding the following aspects of early management strategies in patients with suspected PMR: diagnostic strategies, GCA screening, glucocorticoid initiation prior to referral, value of shared care and value of fast track clinic. METHODS: Two authors performed a systematic literature search, data extraction and risk of bias assessment independently. The literature search was conducted in Embase, MEDLINE (PubMed) and Cochrane. Studies were included if they contained cohorts of suspected PMR patients and evaluated the efficacy of different diagnostic strategies for PMR, screening for giant cell arteritis (GCA), starting glucocorticoids before referral to secondary care, shared care, or fast-track clinics. RESULTS: From 2,437 records excluding duplicates, 14 studies met the inclusion criteria. Among these, 10 studies investigated the diagnostic accuracy of various diagnostic strategies with the majority evaluating different clinical approaches, but none of them showed consistently high performance. However, 4 studies on shared care and fast-track clinics showed promising results, including reduced hospitalization rates, lower starting doses of glucocorticoids, and faster PMR diagnosis. CONCLUSION: This review emphasizes the sparse evidence of early management and referral strategies for patients with suspected PMR. Additionally, screening and diagnostic strategies for differentiating PMR from other diseases, including concurrent GCA, require clarification. Fast-track clinics may have potential to aid patients with PMR in the future, but studies will be needed to determine the appropriate pre-referral work-up.

Risk of somatic diseases in patients with eating disorders: the role of comorbid substance use disorders.

AIMS: Eating disorders (EDs) and substance use disorders (SUDs) often co-occur, and both involve somatic diseases. So far, no study has considered whether comorbid SUDs may impact somatic disease risk in patients with EDs. Therefore, this study aimed to examine the impact of comorbid SUDs on the risk of 11 somatic disease categories in patients with anorexia nervosa (AN), bulimia nervosa (BN) and unspecified eating disorder (USED) compared to matched controls. METHODS: A retrospective cohort study was conducted using Danish nationwide registries. The study population included 20 759 patients with EDs and 83 036 controls matched on month and year of birth, sex and ethnicity. Hazard ratios (HRs) were calculated to compare the risk of being diagnosed with a somatic disease (within 11 categories defined by the ICD-10) following first ED diagnosis (index date) between ED patients and controls both with and without SUDs (alcohol, cannabis or hard drugs). RESULTS: The ED cohort and matched controls were followed for 227 538 and 939 628 person-years, respectively. For ED patients with SUDs, the risk pattern for being diagnosed with different somatic diseases (relative to controls without SUDs) varied according to type of ED and SUD [adjusted HRs ranged from 0.95 (99% CI = 0.57; 1.59) to 4.17 (2.68, 6.47)]. The risk estimates observed among ED patients with SUDs were generally higher than those observed among ED patients without SUDs [adjusted HRs ranged from 1.08 (99% CI = 0.95, 1.22) to 2.56 (2.31, 2.84)]. Abuse of alcohol only had a non-synergistic effect on six disease categories in AN patients and five in BN and USED patients. Abuse of cannabis (with/without alcohol) had a non-synergistic effect on five disease categories in AN and BN patients and two in USED patients. Abuse of hard drugs (with/without alcohol or cannabis) had a non-synergistic effect on nine disease categories in AN patients, eight in BN patients and seven in USED patients. CONCLUSIONS: The present study documents non-synergistic but not synergistic harmful somatic consequences of SUDs among patients with different EDs, with AN and hard drugs being the most predominant factors. Hence, EDs and SUDs did not interact and result in greater somatic disease risk than that caused by the independent effects. Since EDs and SUDs have independent effects on many somatic diseases, it is important to monitor and treat ED patients for SUD comorbidity to prevent exacerbated physical damage in this vulnerable population.

Chlorination for low-cost household water disinfection - A critical review and status in three Latin American countries.

Chlorination has historically provided microbiologically safe drinking water in public water supplies. Likewise, chlorine has also been introduced as a low-cost disinfection method in rural and marginalized communities, both at community and household level, as well as during emergencies. Although this practice is common and well established for use as a household water treatment technology in the Global South, several challenges in effective and efficient implementation still need to be addressed. Here, we explored these issues by a literature review and narrowed them to the status of three Latin American countries (Mexico, Colombia, and Brazil). Overall, it was found that although guidance on household-based chlorination includes information on health risks and hygiene, this may not create enough incentive for the user to adapt the method satisfactorily. Physicochemical quality of the water influences chlorination efficiency and it is found that variations in quality are rarely considered when recommending chlorine doses during implementation. These are far more often based on a few measurements of turbidity, thereby not considering dissolved organic matter, or seasonal and day-to-day variations. Other factors such as user preferences, chlorine product quality and availability also represent potential barriers to the sustainable use of chlorination. For chlorination to become a sustainable household water treatment, more focus should therefore be given to local conditions prior to the intervention, as well as support and maintenance of behavioural changes during and after the intervention.

Type of hormonal treatment administered to induce vitellogenesis in European eel influences biochemical composition of eggs and yolk-sac larvae.

Egg biochemical composition is among the main factors affecting offspring quality and survival during the yolk-sac stage, when larvae depend exclusively on yolk nutrients. These nutrients are primarily embedded in the developing oocytes during vitellogenesis. In aquaculture, assisted reproduction procedures may be applied enabling gamete production. For the European eel (Anguilla anguilla), reproductive treatment involves administration of pituitary extracts from carp (CPE) or salmon (SPE) to induce and sustain vitellogenesis. In the present study, we compared the influence of CPE and SPE treatments on offspring quality and composition as well as nutrient utilization during the yolk-sac stage. Thus, dry weight, proximal composition (total lipid, total protein), free amino acids, and fatty acids were assessed in eggs and larvae throughout the yolk-sac stage, where body and oil-droplet area were measured to estimate growth rate, oil-droplet utilization, and oil-droplet utilization efficiency. The results showed that CPE females spawned eggs with higher lipid and free amino acid contents. However, SPE females produced more buoyant eggs with higher fertilization rate as well as larger larvae with more energy reserves (estimated as oil-droplet area). Overall, general patterns of nutrient utilization were detected, such as the amount of total lipid and monounsaturated fatty acids decreasing from the egg stage and throughout the yolk-sac larval stage. On the contrary, essential fatty acids and free amino acids were retained. Notably, towards the end of the yolk-sac stage, the proximal composition and biometry of surviving larvae, from both treatments, were similar.

Effect of initiating biologics compared to intensifying conventional DMARDs on clinical and MRI outcomes in established rheumatoid arthritis patients in clinical remission: Secondary analyses of the IMAGINE-RA trial.

OBJECTIVES: To compare the effect of treat-to-target-based escalations in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics on clinical disease activity and magnetic resonance imaging (MRI) inflammation in a rheumatoid arthritis (RA) cohort in clinical remission. METHOD: One-hundred patients with established RA, Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP) < 3.2, and no swollen joints (hereafter referred to as 'in clinical remission') who received csDMARDs underwent clinical evaluation and MRI of the wrist and second to fifth metacarpophalangeal joints every 4 months. They followed a 2 year MRI treatment strategy targeting DAS28-CRP ≤ 3.2, no swollen joints, and absence of MRI osteitis, with predefined algorithmic treatment escalation: first: increase in csDMARDs; second: adding a biologic; third: switch biologic. MRI osteitis and Health Assessment Questionnaire (HAQ) (co-primary outcomes) and MRI combined inflammation and Simplified Disease Activity Index (SDAI) (key secondary outcomes) were assessed 4 months after treatment change and expressed as estimates of group differences. Statistical analyses were based on the intention-to-treat population analysed using repeated-measures mixed models. RESULTS: Escalation to first biologic compared to csDMARD escalation more effectively reduced MRI osteitis (difference between least squares means 1.8, 95% confidence interval 1.0-2.6), HAQ score (0.08, 0.03-0.1), MRI combined inflammation (2.5, 0.9-4.1), and SDAI scores (2.7, 1.9-3.5). CONCLUSIONS: Treat-to-target-based treatment escalations to biologics compared to escalation in csDMARDs more effectively improved MRI inflammation, physical function, and clinical disease activity in patients with established RA in clinical remission. Treatment escalation in RA patients in clinical remission reduces clinical and MRI-assessed disease activity. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01656278.

Yoga therapy DYADS: A novel approach to chronic pain management in underserved populations.

Yoga therapy is an emerging integrative health approach that applies the practices and teachings of yoga for individuals with clinical concerns. It is generally offered as individual sessions between a yoga therapist and client or in a small group setting with several clients who share a clinical concern. Here we describe a third model for consideration- the yoga therapy dyad. A dyad includes two clients working simultaneously with a single yoga therapist and differs from both individual and small group sessions in the potential benefits and challenges. The yoga therapy dyad model that is detailed here was implemented as part of a feasibility trial along with group acupuncture therapy for chronic pain in an underserved population. Underserved populations are at risk for pain and reduced access to care. This pilot may inform future research, policy, education, and clinical practice.

The patient enablement instrument for back pain: reliability, content validity, construct validity and responsiveness.

BACKGROUND: Currently, there are no outcome measures assessing the ability of people with non-specific low back pain to self-manage their illness. Inspired by the 'Patient Enablement Instrument', we developed the Patient Enablement Instrument for Back Pain (PEI-BP). The aim of this study was to describe the development of the Patient Enablement Instrument for Back Pain (PEI-BP) and investigate content validity, construct validity, internal consistency, test-retest reliability, measurement error, responsiveness and floor and ceiling effects. METHODS: The PEI-BP consists of 6 items that are rated on a 0-10 Numeric Rating Scale. Measurement properties were evaluated using the COSMIN taxonomy and were based on three cohorts from primary care with low back pain: The content validity cohort (N = 14) which participated in semi-structured interviews, the GLA:D® Back cohort (N = 272) and the test-retest cohort (N = 37) which both completed self-reported questionnaires. For construct validity and responsiveness, enablement was compared to disability (Oswestry Disability Index), back pain beliefs (Brief Illness Perception Questionnaire), fear avoidance (Fear-Avoidance Beliefs Questionnaire-physical activity), mental health (SF-36), educational level and number of previous episodes of low back pain. RESULTS: The PEI-BP was found to have acceptable content validity, construct validity, reliability (internal consistency, test-retest reliability and measurement error) and responsiveness. The Smallest Detectable Change was 10.1 points illustrating that a patient would have to change more than 1/6 of the scale range for it to be a true change. A skewed distribution towards the high scores were found at baseline indicating a potentially problematic ceiling effect in the current population. CONCLUSIONS: The PEI-BP can be considered a valid and reliable tool to measure enablement on people seeking care for non-specific LBP. Further testing of the PEI-BP in populations with more severe LBP is recommended. TRIAL REGISTRATION: Not applicable.

Using IPM-CPR as a Management Program for Apple Orchards.

We have demonstrated how management of key orchard pests including the insect invasive species Halyomorpha halys (Stål) (Hemiptera: Pentatomidae) can be accomplished using a systems-level approach termed IPM-CPR (Integrated Pest Management-Crop Perimeter Restructuring) in apple. We conducted on-farm comparisons of IPM-CPR to standard management program for managing H. halys, Cydia pomonella (L.) (Lepidoptera: Tortricidae), Grapholita molesta (Busck) (Lepidoptera: Tortricidae), and Lygus lineolaris Palisot de Beauvois (Hemiptera: Miridae) in commercial apple orchards in 2014, 2016, and 2017 in New Jersey, Maryland, and Virginia. The presence and abundance of key pests and fruit injury at harvest were used as a measure of success of the program. We compared the amount of insecticide applied for each management program. In majority of instances, there were no differences in the IPM-CPR and the standard management program in terms of H. halys numbers in baited pyramid traps and stink bug injury at harvest. Damage from C. pomonella and G. molesta in the IPM-CPR treatment was significantly lower than the standard management program in 2014 and 2017. Amount of active ingredient used was on average 62.1% lower in the IPM-CPR treatment compared with standard management program. Despite a reduction in insecticide use, there were minimal impacts on beneficial insects. Overall, IPM-CPR in apples successfully managed key orchard pests, including H. halys, and used significantly less insecticide than a standard insecticide-based management program and could be adopted as a systems-level approach for pest population reduction.

Similar glycaemic control with less nocturnal hypoglycaemia in a 38-week trial comparing the IDegAsp co-formulation with insulin glargine U100 and insulin aspart in basal insulin-treated subjects with type 2 diabetes mellitus.

AIMS: To confirm non-inferiority of insulin degludec/insulin aspart (IDegAsp) once-daily (OD) versus insulin glargine (IGlar) U100 OD + insulin aspart (IAsp) OD for HbA1c after 26 weeks, and compare efficacy and safety between groups at W26 + W38. METHODS: A 38-week, randomised, open-label, treat-to-target (HbA1c < 7.0%) trial in adults with type 2 diabetes mellitus (on basal insulin ±â€¯oral antidiabetic drugs; HbA1c 7.0-10.0%). Randomisation (1:1): IDegAsp or IGlar U100 + IAsp. Intensification to IDegAsp twice daily (BID) was permitted at W26 + W32, or with additional IAsp injections at W26 (maximum IAsp BID) or W32 (maximum IAsp three-times daily). RESULTS: For W0-W26, mean percentage-change (standard deviation) HbA1c was: IDegAsp, -1.1 (0.9); IGlar U100 + IAsp, -1.1 (0.8); estimated treatment difference: 0.07% (95% confidence interval [CI]: -0.06; 0.21) confirmed non-inferiority. At W26 and W38, target HbA1c achievement, and mean fasting and postprandial glucose were similar across groups. At W38, more subjects achieved target HbA1c without hypoglycaemia with IDegAsp (22.5%) than with IGlar U100 + IAsp (21.1%), with significantly fewer nocturnal episodes (W0-W38, estimated rate ratio: 0.61 [95% CI: 0.40; 0.93]). Safety profiles were similar across treatment groups throughout. CONCLUSIONS: IDegAsp OD/BID are effective treatment intensification options versus multiple injection basal-bolus therapies, achieving similar glycaemic control, with significantly less nocturnal hypoglycaemia.

Inhibition of Small Conductance Calcium-Activated Potassium (SK) Channels Prevents Arrhythmias in Rat Atria During ß-Adrenergic and Muscarinic Receptor Activation.

Sympathetic and vagal activation is linked to atrial arrhythmogenesis. Here we investigated the small conductance Ca2+-activated K+ (SK)-channel pore-blocker N-(pyridin-2-yl)-4-(pyridine-2-yl)thiazol-2-amine (ICA) on action potential (AP) and atrial fibrillation (AF) parameters in isolated rat atria during ß-adrenergic [isoprenaline (ISO)] and muscarinic M2 [carbachol (CCh)] activation. Furthermore, antiarrhythmic efficacy of ICA was benchmarked toward the class-IC antiarrhythmic drug flecainide (Fleca). ISO increased the spontaneous beating frequency but did not affect other AP parameters. As expected, CCh hyperpolarized resting membrane potential (-6.2 ± 0.9 mV), shortened APD90 (24.2 ± 1.6 vs. 17.7 ± 1.1 ms), and effective refractory period (ERP; 20.0 ± 1.3 vs. 15.8 ± 1.3 ms). The duration of burst pacing triggered AF was unchanged in the presence of CCh compared to control atria (12.8 ± 5.3 vs. 11.2 ± 3.6 s), while ß-adrenergic activation resulted in shorter AF durations (3.3 ± 1.7 s) and lower AF-frequency compared to CCh. Treatment with ICA (10 µM) in ISO -stimulated atria prolonged APD90 and ERP, while the AF burden was reduced (7.1 ± 5.5 vs. 0.1 ± 0.1 s). In CCh-stimulated atria, ICA treatment also resulted in APD90 and ERP prolongation and shorter AF durations. Fleca treatment in CCh-stimulated atria prolonged APD90 and ERP and abbreviated the AF duration to a similar extent as with ICA. Muscarinic activated atria constitutes a more arrhythmogenic substrate than ß-adrenoceptor activated atria. Pharmacological inhibition of SK channels by ICA is effective under both conditions and equally efficacious to Fleca.

A comparative analysis of heterogeneity in commercially available recombinant factor VIII products.

INTRODUCTION: Advances in analytical technologies enable investigation of possible correlations between molecular structure, aggregation and subvisible particle content. Regulatory agencies place increasing attention on potential risks associated with protein aggregates in the micron range in biological therapeutics. AIM: Assess the heterogeneity, high-molecular-weight protein (HMWP) species, subvisible particle content and posttranslational modifications in six commercially available recombinant FVIII (rFVIII) products. METHODS: Three B-domain-deleted (BDD) or B-domain truncated rFVIII products (turoctocog alfa, simoctocog alfa and moroctocog alfa) and three full-length rFVIII products (octocog alfa FS and two octocog alfa) were analysed. HMWP content, amount of micron range subvisible particles, tyrosine-1680 sulphation and N-glycan analysis were investigated. RESULTS: The B-domain-modified products had more protein size homogeneity vs the full-length products. Size exclusion-high-performance liquid chromatography data indicated no association between B-domain structure and aggregate content or size of the products tested. The rFVIII products showed large variation in subvisible particle concentration, with turoctocog alfa and simoctocog alfa having the lowest numbers (1000-1600 and 1800-2400 particles/100 IU, respectively). Turoctocog alfa and simoctocog alfa displayed the most complete tyrosine sulphation (>99.5%). CONCLUSION: Overall, there was no association between molecular structure (full-length B-domain, BDD or truncated) and subvisible particle or HMWP content. Dissimilarities may be related to production and product handling differences. In this study, turoctocog alfa, such as simoctocog alfa, had one of the lowest levels of subvisible particles and HMWP content, and high protein size homogeneity.

Composition in the Interface between Clay Mineral Surfaces and Divalent Cation Electrolytes.

The interfacial free energy of a solid, which determines its adsorption properties, depends on interactions between the surface and the fluid. A change in surface composition can completely change the behavior of the solid. Decades of work have explored adsorption and its effects at solid-fluid interfaces from the macroscopic perspective and using molecular modeling, so the concept of the electric double layer (EDL) is well established in the community. However, direct, molecular level, experimental observations of the composition within the interface region, and its change with time and conditions, are not abundant. We used cryogenic X-ray photoelectron spectroscopy (cryoXPS) to observe the composition in the clay mineral-solution interface region as a function of bulk solution composition, on illite and chlorite in MgCl2 and CaCl2 electrolytes, over a range of concentrations (1-125 mM), in situ, on vitrified samples. These samples were prepared from very thin smears of centrifuged wet paste that were instantaneously chilled to liquid N2 temperature. They preserved the adsorbed solution in its amorphous state, maintaining the location of the ions and water with respect to the solid, without the disruption that occurs during drying or the rearrangement that results as water crystallizes during freezing. With decreasing ionic strength, we could directly monitor the loss of negative charge in the interface region, producing an anion deficiency, as predicted by theory. The Cl-/Me2+ ratio dropped below 1 for chlorite at 12-25 mM MeCl2 and for illite at 75-100 mM. In addition to better understanding of clay mineral behavior in solution, this work demonstrates that only those clay minerals where surface charge density is the same or lower than that for chlorite contribute to a low salinity enhanced oil recovery response (LS EOR). This explains many of the contradictory results from studies about the role of clay minerals in LS EOR.