Significantly improved dielectric properties of multiwall carbon nanotube-BaTiO3/PVDF polymer composites by tuning the particle size of the ceramic filler

The effects of different BaTiO₃ sizes (≈100 nm (nBT) and 0.5–1.0 μm (μBT)) on the dielectric and electrical properties of multiwall carbon nanotube (CNT)-BT/poly(vinylidene fluoride) (PVDF) composites are investigated. The fabricated three-phase composites using 20 vol% BT with various CNT volume fractions (f_CNT) are systematically characterized. The dielectric permittivity (ε′) of the CNT-nBT/PVDF and CNT-μBT/PVDF composites rapidly increases when f_CNT > 0.015 and f_CNT > 0.017, respectively. The former is accompanied by the dramatic increase in the loss tangent (tan δ) and conductivity (σ), but surprisingly, not for the latter. At 10³ Hz, the low tan δ and σ values of the CNT-μBT/PVDF composite are about 0.06 and 6.82 × 10⁻⁹ S cm⁻¹, while its ε′ value is greatly enhanced (≈154.6). The variation of the dielectric permittivity with f_CNT for both composite systems follows the percolation model with percolation thresholds of f_c = 0.018 and f_c = 0.02, respectively. With further increasing f_CNT to 0.02, ε′ is greatly increased to 253.8, while tan δ ≤ 0.1. Without μBT particles, the ε′ and tan δ values of the CNT/PVDF composite with f_CNT = 0.02 are as high as ≈240 and >10³, respectively. Greatly enhanced dielectric properties are described in detail.

The effects of different BaTiO₃ sizes (≈100 nm (nBT) and 0.5–1.0 μm (μBT)) on the dielectric and electrical properties of multiwall carbon nanotube (CNT)-BT/poly(vinylidene fluoride) (PVDF) composites are investigated.     

Frequency of cardioversions as an additional risk factor for stroke in atrial fibrillation – the FinCV-4 study

BackgroundPatients with atrial fibrillation (AF) are selected for oral anticoagulation based on individual patient characteristics. There is little information on how clinical AF burden associates with the risk of ischaemic stroke or systemic embolism (SSE). The aim of this study was to explore the association of the frequency of cardioversions (CV) as a measure of clinical AF burden on the long-term SSE risk, with a focus on patients at intermediate stroke risk based on CHA₂DS₂-VASc score. For these patients, additional SSE risk stratification by assessing CV frequency may aid in the decision on whether to initiate oral anticoagulation.MethodsThis retrospective analysis of FinCV Study from years 2003–2010 included 2074 patients who were not using any oral anticoagulation (long term or temporary) after CVs and undergoing a total of 6534 CVs for AF from emergency departments of three hospitals. Two study groups were formed: high CV frequency (mean interval between CVs ≤12 months and low frequency (>12 months).ResultsA total of 107 SSEs occurred during a mean follow-up of 5.4 years. The event rates per 100 patient-years were 1.82 and 0.67 in high versus low CV frequency groups, respectively. After adjustment for CHA₂DS₂-VASc score, CV frequency independently predicted SSE (HR, 2.87 [95% CI, 1.47 to 5.64]; p = .002) at 3 years. Competing risk analysis also identified CV frequency (sHR, 2.70 [95% CI, 1.38–5.31]; p = .004) as an independent predictor for SSE. In patients with CHA₂DS₂-VASc score 1 and low CV frequency, the SSE risk was only 0.08 per 100 patient-years.ConclusionsFrequency of CVs for symptomatic AF episodes provides additional information on stroke risk in AF patients with CHA₂DS₂-VASc score 1.

Key messages

• This retrospective study offers a unique opportunity to observe the natural course of AF patients with infrequent episodes of clinical arrhythmia when they were not using OAC (before introduction of CHA₂DS₂-VASc score).
• Stroke or systemic embolism rate was very low (0.08 per 100 patient-years) in patients with one CHA₂DS₂-VASc point who visited the emergency room for cardioversion less than once a year.
• Frequency of cardioversions can be used for additional risk stratification in patients at intermediate risk of stroke based on CHA₂DS₂-VASc score.

     

Cognitive processing of cluster headache patients: evidence from event-related potentials

Background

The peripheral and central origins of pain in cluster headache (CH) have been a matter of much debate. The development and application of functional imaging techniques have provided more evidence supporting the hypothesis that CH is not a disorder exclusively peripheral in origin, and in fact central regions might be more important. Event-related potentials confer advantages in the functional evaluation of the cortex, but few studies thus far have employed this method in cluster headache.

Methods

Seventeen cluster patients (15 males; mean age = 35.4 years) and 15 age-matched healthy participants (13 males; mean age = 34.6 years) were recruited. A visual oddball paradigm was employed to analyze target processing using event-related potentials. We investigated the P3/P3d components in the experiment.

Results

P3/P3d amplitudes were decreased in CH patients (P3, 3.82 μV; P3d, 5.8 μV) compared with controls (P3, 7.28 μV; P3d, 8.95 μV), F(1,30) = 4.919, p < 0.05, η2 = 0.141 for P3 and F(1,30) = 8.514, p < 0.05, η2 = 0.221 for P3d, respectively). Moreover, the amplitudes of P3/P3d were no significantl difference in the side of pain as compared to contralateral one (p > 0.05).

Conclusions

These results provide evidence of dysfunction in the cognitive processing of CH patients, which may also contribute to the pathophysiology of CH.     

Tunable magnetic ground states of iron monolayer on nonmagnetic metallic substrates by small in-plane strains

The magnetic states of one single atomic layer of iron epitaxially grown on 4d and 5d nonmagnetic metals are studied under strain systematically using first principle calculations. Our results show that, without strain, the iron on top of different 4d and 5d nonmagnetic metals shows distinct antiferromagnetic or ferromagnetic ground states: a parallel antiferromagnetic ground state (p-AFM) on Rh and a central antiferromagnetic ground state (c-AFM) on Ir and ferromagnetic (FM) ground state on Pd, Ag, Pt and Au. However, when introducing in-plane biaxial and uniaxial strain (Δε_xx) on the substrates, the ground state of iron can be manipulated easily. In detail, for biaxial strain, the ground state of iron on an Rh substrate becomes FM when Δε_xx < −2.0% and c-AFM when Δε_xx > 0.8%, and on an Ir substrate, the ground state of iron becomes FM when Δε_xx < −2.8% and c-AFM when Δε_xx > –0.8%. However, for the uniaxial strain along the x direction, while using the corresponding Poisson''s ratios to determine the strain along the y direction, the ground state of iron on an Rh substrate remains the p-AFM state, but on an Ir substrate, the ground state of iron changes from c-AFM to p-AFM at Δε_xx = 0.2% or Δε_xx = −0.3% along the x direction respectively.

The magnetic states of one single atomic layer of iron epitaxially grown on 4d and 5d nonmagnetic metals are studied under strain systematically using first principle calculations.     

T1 mapping of the myocardium: Intra-individual assessment of the effect of field strength,cardiac cycle and variation by myocardial region

Background

Myocardial T1 relaxation time (T1 time) and extracellular volume fraction (ECV) are altered in the presence of myocardial fibrosis. The purpose of this study was to evaluate acquisition factors that may result in variation of measured T1 time and ECV including magnetic field strength, cardiac phase and myocardial region.

Methods

31 study subjects were enrolled and underwent one cardiovascular MR exam at 1.5 T and two exams at 3 T, each on separate days. A Modified Look-Locker Inversion Recovery (MOLLI) sequence was acquired before and 5, 10, 12, 20, 25 and 30 min after administration of 0.15 mmol/kg gadopentetate dimeglumine (Gd-DTPA; Magnevist) at 1.5 T (exam 1). For exam 2, MOLLI sequences were acquired at 3 T both during diastole and systole, before and after administration of Gd-DTPA (0.15 mmol/kg Magnevist).Exam 3 was identical to exam 2 except gadobenate dimeglumine was administered (Gd-BOPTA; 0.1 mmol/kg Multihance). T1 times were measured in myocardium and blood. ECV was calculated by (ΔR1_myocardium/ΔR1_blood)*(1-hematocrit)_.

Results

Before gadolinium, T1 times of myocardium and blood were significantly greater at 3 T versus 1.5 T (28% and 31% greater, respectively, p < 0.001); after gadolinium, 3 T values remained greater than those at 1.5 T (14% and 12% greater for myocardium and blood at 3 T with Gd-DTPA, respectively, p < 0.0001 and 18% and 15% greater at 3 T with Gd-BOPTA, respectively, p < 0.0001). However, ECV did not vary significantly with field strength when using the same contrast agent at equimolar dose (p = 0.2). Myocardial T1 time was 1% shorter at systole compared to diastole pre-contrast and 2% shorter at diastole compared to systole post-contrast (p < 0.01). ECV values were greater during diastole compared to systole on average by 0.01 (p < 0.01 to p < 0.0001). ECV was significantly higher for the septum compared to the non-septal myocardium for all three exams (p < 0.0001-0.01) with mean absolute differences of 0.01, 0.004, and 0.07, respectively, for exams 1, 2 and 3.

Conclusion

ECV is similar at field strengths of 1.5 T and 3 T. Due to minor variations in T1 time and ECV during the cardiac cycle and in different myocardial regions, T1 measurements should be obtained at the same cardiac phase and myocardial region in order to obtain consistent results.     

Are standard doses of piperacillin sufficient for critically ill patients with augmented creatinine clearance?

IntroductionThe aim of this study was to explore the impact of augmented creatinine clearance and differing minimum inhibitory concentrations (MIC) on piperacillin pharmacokinetic/pharmacodynamic (PK/PD) target attainment (time above MIC (fT_>MIC)) in critically ill patients with sepsis receiving intermittent dosing.MethodsTo be eligible for enrolment, critically ill patients with sepsis had to be receiving piperacillin-tazobactam 4.5 g intravenously (IV) by intermittent infusion every 6 hours for presumed or confirmed nosocomial infection without significant renal impairment (defined by a plasma creatinine concentration greater than 171 μmol/L or the need for renal replacement therapy). Over a single dosing interval, blood samples were drawn to determine unbound plasma piperacillin concentrations. Renal function was assessed by measuring creatinine clearance (CL_CR). A population PK model was constructed, and the probability of target attainment (PTA) for 50% and 100% fT_>MIC was calculated for varying MIC and CL_CR values.ResultsIn total, 48 patients provided data. Increasing CL_CR values were associated with lower trough plasma piperacillin concentrations (P < 0.01), such that with an MIC of 16 mg/L, 100% fT_>MIC would be achieved in only one-third (n = 16) of patients. Mean piperacillin clearance was approximately 1.5-fold higher than in healthy volunteers and correlated with CL_CR (r = 0.58, P < 0.01). A reduced PTA for all MIC values, when targeting either 50% or 100% fT_>MIC, was noted with increasing CL_CR measures.ConclusionsStandard intermittent piperacillin-tazobactam dosing is unlikely to achieve optimal piperacillin exposures in a significant proportion of critically ill patients with sepsis, owing to elevated drug clearance. These data suggest that CL_CR can be employed as a useful tool to determine whether piperacillin PK/PD target attainment is likely with a range of MIC values.     

TLC-smartphone in antibiotics determination and low-quality pharmaceuticals detection

Thin layer chromatography (TLC) is a powerful and simple technique for screening and quantifying low quality and counterfeit pharmaceutical products. The detection methods used to detect and quantify separate analytes in TLC ranges from the densitometric method to mass spectrometric or Raman spectroscopic methods. This work describes the development and optimization of a simple and sensitive TLC method utilizing a smartphone CCD camera for verification of both identity and quantity of antibiotics in dosage form, namely ofloxacin and ornidazole. Mixtures of ofloxacin and ornidazole were chromatographed on a silica gel 60 F₂₅₄ plate as a stationary phase. The optimized mobile phase is n-butanol : methanol : ammonia (8 : 1 : 1.5 by volume). Iodine vapor has been used as a “universal stain” to visualize the spots on the TLC plates in order to obtain a visual image using the smartphone camera and a desk lamp as an illumination source, thus eliminating the need for a UV illumination source. The recorded images were processed to calculate the R_f values (R_f values for ofloxacin and ornidazole were 0.12 and 0.76, respectively) which provide identity of the drugs while spot intensity was calculated using a commercially available smartphone app and employed for quantitative analysis of the antibiotics and “acetaminophen” as an example of a counterfeit substance. The smartphone TLC method yielded a linearity of ofloxacin and ornidazole in the range of 12.5–62.5 μg/band and 500–1000 μg/band, respectively. The limit of detection was found to be 1.6 μg/spot for ofloxacin and 97.8 μg/spot for ornidazole. The proposed method was compared with the bench top densitometric method for verification using a Camag TLC Scanner 3, the spot areas were scanned at 320 nm. The R_f value of ofloxacin and ornidazole was calculated to be 0.12 and 0.76, respectively. The densitometric method yielded a linearity of ofloxacin and ornidazole in the range of 5–40 μg/band and 5–50 μg/band, respectively. The limit of detection was found to be 0.8 μg/spot for ofloxacin and 1.1 μg/spot for ornidazole. The proposed method has been successfully applied for the determination of ofloxacin and ornidazole present in more than one pharmaceutical dosage form and was comparable to the densitometric method.

Low-quality and counterfeit pharmaceutical detection has been performed based on the processing of an iodine stained TLC plate image captured by a smartphone CCD camera.     

Hemodynamics of the sternocleidomastoid measured with frequency domain near-infrared spectroscopy towards non-invasive monitoring during mechanical ventilation

Mechanical ventilation (MV) is used to assist spontaneous breathing in critically ill patients in the intensive care unit (ICU). MV is a cornerstone of critical care medicine but it is now known that inspiratory muscle dysfunction due to injury, disuse, and/or atrophy during MV plays a major role in outcomes for these patients. For example, prolonged MV is strongly correlated with dysfunction of the sternocleidomastoid (SCM), an accessory inspiratory muscle that has been linked to weaning failure from MV. Hemodynamic monitoring of the SCM may provide an important non-invasive and real-time means to monitor MV. In this work, we first conducted multi-layer Monte Carlo simulations to confirm the ability of near infrared light to detect changes in the oxygenation of the SCM over wide ranges of skin tones and adipose layer thicknesses. We then optimized a custom digital frequency domain near-infrared spectroscopy (FD-NIRS) system for continuous 10 Hz measurements of the SCM at 730 nm and 850 nm. A healthy volunteer study was conducted (N=10); subjects performed sets of isometric neck flexions of the SCM. Substantial changes in oxyhemoglobin + oxymyoglobin (oxy[Hb + Mb]), deoxyhemoglobin + deoxymyoglobin (deoxy[Hb + Mb]), and total hemoglobin + myoglobin (total[Hb + Mb]) were observed during sustained and intermittent isometric flexions. There were notable sex differences observed in the magnitude of hemodynamic changes (∼2x larger changes in males for oxy[Hb + Mb] and deoxy[Hb + Mb]). The magnitude of hemodynamic changes when taking into account µ_s′ changes during flexions was ∼ 2-2.5x larger as compared to assuming constant scattering (CS), which is a common assumption used for continuous wave (CW) NIRS methods. This study suggests that FD-NIRS provides improved accuracy for hemodynamic monitoring of the SCM compared to CW-NIRS, and that FD-NIRS may provide value for SCM monitoring during MV.     

Copper–cobalt catalysts supported on mechanically mixed HZSM-5 and γ-Al2O3 for higher alcohols synthesis via carbon monoxide hydrogenation

Mechanically mixed γ-Al₂O₃ and HZSM-5 (Si/Al = 50) with different mass ratio were utilized as support for Cu–Co higher alcohol synthesis catalysts prepared through incipient wetness impregnation. The textural and structural properties were studied using Ar low temperature adsorption and desorption, H₂-temperature programmed reduction (H₂-TPR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscope (TEM) and catalytic performance measurements. The results indicated that the mechanically mixed HZSM-5 and γ-Al₂O₃ supported copper–cobalt catalysts were superior to either γ-Al₂O₃ or HZSM-5 supported ones with the same metal loading. The results revealed that using HZSM-5 and γ-Al₂O₃ mechanically mixed benefited the dispersion of metallic phases and stronger synergetic functions between smaller nanoparticles containing copper and/or cobalt, which is essential for HAS from CO hydrogenation. Under working conditions of P = 5.0 MPa, T = 300 °C, V(H₂) : V(CO) : V(N₂) = 4 : 2 : 1 and GHSV = 7200 mL g⁻¹ h⁻¹, mechanically mixed HZSM-5 and γ-Al₂O₃ supported catalysts showed higher catalytic activity than those over single support. For CuCo catalysts upon support containing 50.0 wt% HZSM-5 and 50.0 wt% γ-Al₂O₃, the CO conversion was 21.3% and the C₂₊ alcohol selectivity was 41.8%.

CuCo bimetallic catalysts over the mixed supports showed smaller average particle size, better dispersion of cobalt and copper species, and good activity for higher alcohols synthesis.     

Racemic ketamine in adult head injury patients: use in endotracheal suctioning

Introduction

Endotracheal suctioning (ETS) is essential for patient care in an ICU but may represent a cause of cerebral secondary injury. Ketamine has been historically contraindicated for its use in head injury patients, since an increase of intracranial pressure (ICP) was reported; nevertheless, its use was recently suggested in neurosurgical patients. In this prospective observational study we investigated the effect of ETS on ICP, cerebral perfusion pressure (CPP), jugular oxygen saturation (SjO₂) and cerebral blood flow velocity (mVMCA) before and after the administration of ketamine.

Methods

In the control phase, ETS was performed on patients sedated with propofol and remifentanil in continuous infusion. If a cough was present, patients were assigned to the intervention phase, and 100 γ/kg/min of racemic ketamine for 10 minutes was added before ETS.

Results

In the control group ETS stimulated the cough reflex, with a median cough score of 2 (interquartile range (IQR) 1 to 2). Furthermore, it caused an increase in mean arterial pressure (MAP) (from 89.0 ± 11.6 to 96.4 ± 13.1 mmHg; P <0.001), ICP (from 11.0 ± 6.7 to 18.5 ± 8.9 mmHg; P <0.001), SjO₂ (from 82.3 ± 7.5 to 89.1 ± 5.4; P = 0.01) and mVMCA (from 76.8 ± 20.4 to 90.2 ± 30.2 cm/sec; P = 0.04). CPP did not vary with ETS. In the intervention group, no significant variation of MAP, CPP, mVMCA, and SjO₂ were observed in any step; after ETS, ICP increased if compared with baseline (15.1 ± 9.4 vs. 11.0 ± 6.4 mmHg; P <0.05). Cough score was significantly reduced in comparison with controls (P <0.0001).

Conclusions

Ketamine did not induce any significant variation in cerebral and systemic parameters. After ETS, it maintained cerebral hemodynamics without changes in CPP, mVMCA and SjO₂, and prevented cough reflex. Nevertheless, ketamine was not completely effective when used to control ICP increase after administration of 100 γ/kg/min for 10 minutes.     

The role of headache chronicity among predictors contributing to quality of life in patients with migraine: a hospital-based study

Background

Headache chronicity has been known to elicit deleterious effects on quality of life (QOL). We evaluated the contribution of headache chronicity to QOL in relation to clinical, psychiatric, and psychosocial variables in patients with migraine.

Methods

Subjects were recruited from a headache clinic and completed self-report questionnaires including the Migraine Disability Assessment (MIDAS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Migraine-Specific Quality of Life (MSQoL). We obtained predictors of MSQoL by multiple regression analyses. A path analysis model was constructed to analyze interrelationships between the variables.

Results

Among 251 eligible patients, 183 (72.9%) had episodic migraine (EM) and 68 (27.1%) had chronic migraine (CM). Patients with CM had more serious clinical, psychiatric, and poor QOL than did patients with EM. The strongest predictor of the MSQoL score in all patients with migraine was the BDI score (β = -0.373, p < 0.001), followed by the MIDAS score (β = -0.223, p < 0.001), female gender (β = -0.192, p < 0.001), attack duration (β = -0.159, p = 0.001), and headache chronicity (β = -0.130, p = 0.012). Headache chronicity had a direct effect on the MSQoL score and exerted an indirect effect on the MSQoL score through the MIDAS and the BDI scores.

Conclusions

Chronic migraine appears to impair QOL directly as well as indirectly by provoking disability and depression.     

Structure characterization and anticoagulant activity of a novel polysaccharide from Leonurus artemisia (Laur.) S. Y. Hu F

An acidic polysaccharide, named LAP-1, was extracted and isolated from Leonurus artemisia (Laur.), and was further purified with ion exchange chromatography and gel chromatography. The extraction conditions of the crude polysaccharides were optimized by single-factor experiments and response surface methodology. The primary structure of the purified polysaccharide was measured by FT-IR, GC-MS, and NMR. The results showed that LAP-1 was mainly composed of galacturonic acid (GalA), mannose (Man), xylose (Xyl), rhamnose (Rha), arabinose (Ara), glucose (Glc), galactose (Gal), fucose (Fuc), ribose (Rib), and glucuronic acid (GlcA) in the molar ratio of 8.74 : 3.45 : 1.02 : 1 : 2.11 : 5.60 : 4.73 : 1.08 : 1.09 : 1.47. Primary structure analysis results indicated that LAP-1 contained characteristic glycosyl linkages such as →1)-α-d-Manp, →1)-α-d-Glcp, →1)-α-d-Arap-(2→, →1)-β-d-Galp-(3→, →1)-β-d-Manp-(4→, →1)-β-d-Galp-(4→, →1)-β-d-Glcp-(4→, →1)-β-d-GalAp-(4→, →1)-β-d-GlcAp-(4→, →1)-β-d-Manp-(4,6→, →1)-β-d-Manp-(3,4→. The M_w/M_n (PDI), M_n, M_z and M_w of LAP-1 were determined to be 1.423, 6.979 × 10³ g mol⁻¹, 1.409 × 10⁴ g mol⁻¹, and 9.930 × 10³ g mol⁻¹ by HPSEC-MALLS-RID and DLS. SEM, TEM and AFM results indicated that LAP-1 was a highly branched structure. LAP-1 showed mild anticoagulant activity, low toxicity, and less spontaneous bleeding compared with heparin sodium. These results demonstrated the effective coagulation activity of Leonurus artemisia polysaccharides. Thus, the purified LAP-1 could be explored as a promising anticoagulant agent for the treatment of coagulation disorders.

An acidic polysaccharide, denoted LAP-1 was extracted, isolated and purified from Leonurus artemisia (Laur.), in addition to its structure and anticoagulant activity were explored.     

Pyrazolo[1,5-a]pyrimidines-based fluorophores: a comprehensive theoretical-experimental study

Fluorescent molecules are crucial tools for studying the dynamics of intracellular processes, chemosensors, and the progress of organic materials. In this study, a family of pyrazolo[1,5-a]pyrimidines (PPs) 4a–g has been identified as strategic compounds for optical applications due to several key characteristics such as their simpler and greener synthetic methodology (RME: 40–53%) as compared to those of BODIPYS (RME: 1.31–17.9%), and their tunable photophysical properties (going from ε = 3320 M⁻¹ cm⁻¹ and ϕ_F = 0.01 to ε = 20 593 M⁻¹ cm⁻¹ and ϕ_F = 0.97), in which electron-donating groups (EDGs) at position 7 on the fused ring improve both the absorption and emission behaviors. The PPs bearing simple aryl groups such as 4a (4-Py), 4b (2,4-Cl₂Ph), 4d (Ph) and 4e (4-MeOPh), allow good solid-state emission intensities (QY_SS = 0.18 to 0.63) in these compounds and thus, solid-state emitters can be designed by proper structural selection. The properties and stability found in 4a–g are comparable to commercial probes such as coumarin-153, prodan and rhodamine 6G. Ultimately, the electronic structure analysis based on DFT and TD-DFT calculations revealed that EDGs at position 7 on the fused ring favor large absorption/emission intensities as a result of the ICT to/from this ring; however, these intensities remain low with electron-withdrawing groups (EWGs), which is in line with the experimental data and allows us to understand the optical properties of this fluorophore family.

A family of 7-aryl-3-methylpyrazolo[1,5-a]pyrimidines have been identified as strategic compounds for optical applications by a comprehensive theoretical-experimental study.     

Levosimendan attenuates multiple organ injury and improves survival in peritonitis-induced septic shock: studies in a rat model

Introduction

The aim of this study was to investigate the effects of levosimendan on rodent septic shock induced by cecal ligation and puncture (CLP).

Methods

Three hours after peritonitis-induced sepsis, male Wistar rats were randomly assigned to receive an intravenous infusion of levosimendan (1.2 μg/kg/min for 10 min and then 0.3 μg/kg/min for 6 h) or an equivalent volume of saline and vehicle (5% dextrose) solution.

Results

The levosimendan-treated CLP animals had significantly higher arterial pressure and lower biochemical indices of liver and kidney dysfunction compared to the CLP animals (P < 0.05). Plasma interleukin-1β, nitric oxide and organ superoxide levels in the levosimendan-treated CLP group were less than those in CLP rats treated with vehicle (P < 0.05). In addition, the inducible nitric oxide synthase (iNOS) in lung and caspase-3 expressions in spleen were significantly lower in the levosimendan-treated CLP group (P < 0.05). The administration of CLP rats with levosimendan was associated with significantly higher survival (61.9% vs. 40% at 18 h after CLP, P < 0.05). At postmortem examination, the histological changes and neutrophil filtration index in liver and lung were significantly attenuated in the levosimendan-treated CLP group (vs. CLP group, P < 0.05).

Conclusions

In this clinically relevant model of septic shock induced by fecal peritonitis, the administration of levosimendan had beneficial effects on haemodynamic variables, liver and kidney dysfunction, and metabolic acidosis. (1) Lower levels of interleukin-1β, nitric oxide and superoxide, (2) attenuation of iNOS and caspase-3 expressions, and (3) decreases of neutrophil infiltration by levosimendan in peritonitis-induced sepsis animals suggest that anti-inflammation and anti-apoptosis effects of levosimendan contribute to prolonged survival.     

Accuracy of oxygen saturation and total hemoglobin estimates in the neonatal brain using the semi-infinite slab model for FD-NIRS data analysis

Frequency domain near-infrared spectroscopy (FD-NIRS) is a non-invasive method for measuring optical absorption in the brain. Common data analysis procedures for FD-NIRS data assume the head is a semi-infinite, homogenous medium. This assumption introduces bias in estimates of absorption (μ_a), scattering ( μs′), tissue oxygen saturation (S_tO₂), and total hemoglobin (HbT). Previous works have investigated the accuracy of recovered μ_a values under this assumption. The purpose of this study was to examine the accuracy of recovered S_tO₂ and HbT values in FD-NIRS measurements of the neonatal brain. We used Monte Carlo methods to compute light propagation through a neonate head model in order to simulate FD-NIRS measurements at 690 nm and 830 nm. We recovered μ_a, μs′, S_tO₂, and HbT using common analysis procedures that assume a semi-infinite, homogenous medium and compared the recovered values to simulated values. Additionally, we characterized the effects of curvature via simulations on homogenous spheres of varying radius. Lastly, we investigated the effects of varying amounts of extra-axial fluid. Curvature induced underestimation of μ_a, μs′, and HbT, but had minimal effects on S_tO₂. For the morphologically normal neonate head model, the mean absolute percent errors (MAPE) of recovered μ_a values were 12% and 7% for 690 nm and 830 nm, respectively, when source-detector separation was at least 20 mm. The MAPE for recovered S_tO₂ and HbT were 6% and 9%, respectively. Larger relative errors were observed (∼20–30%), especially as S_tO₂ and HbT deviated from normal values. Excess CSF around the brain caused very large errors in μ_a, μs′, and HbT, but had little effect on S_tO₂.OCIS codes: (170.3660) Light propagation in tissues, (170.5380) Physiology, (300.0300) Spectroscopy     

The causal relationships between obstructive sleep apnea and elevated CRP and TNF-α protein levels

BackgroundObstructive sleep apnea (OSA) and inflammation are closely related. This study aimed to evaluate the associations and causal effect between C-reactive protein (CRP) and tumour necrosis factor-alpha (TNF-α) levels and OSA.MethodsPooled analysis was conducted to compare the expression differences of CRP and TNF-α between OSA patients with different severity and controls, and between continuous positive airway pressure (CPAP) and non-CPAP interventions for OSA patients. Using published GWAS summary statistics, we conducted a bidirectional two-sample Mendelian Randomization (MR) to estimate the causal relationships between CRP and TNF-α levels and OSA risk. Effect estimates were evaluated using inverse-variance weighted (IVW) as primary method, and several other MR methods as sensitivity analysis.ResultsBoth TNF-α (WMD [95%CI] = 5.86 [4.80–6.93] pg/ml, p < .00001) and CRP (WMD [95%CI] = 2.66 [2.15–3.17] mg/L, p < .00001), showed a significant increase in OSA patients compared with controls and this increasing trend was associated with OSA severity. Besides, compared to blank control (non-CPAP), CPAP treatment can reduce high TNF-α (WMD [95%CI]= −4.44 [−4.81, −4.07]pg/ml, p < .00001) and CRP (WMD [95%CI]= −0.91 [−1.65, −0.17] mg/l, p = .02) in OSA. Moreover, the primary MR analysis by IVW showed that OSA was the genetically predicted cause of elevated CRP (estimate: 0.095; 95% CI, [0.010–0.179]; p = .029) using six SNPs as the instrument variable, which were repeated by weighted median (estimate: 0.053; 95% CI, [0.007, 0.100]; p =.024) and MR RAPS (estimate: 0.109; 95% CI, [0.079, 0.140]; p = 1.98x10⁻¹²). Besides, the causal effect from elevated CRP on increased OSA risk was almost significant by IVW (OR:1.053; 95% CI, [1.000, 1.111]; p = .053). However, there were no causal associations between TNF-α and OSA from both directions.ConclusionsIncreased CRP and TNF-α were associated with OSA severity and sensible to CPAP treatment. Also, OSA had a suggestive causal effect on elevated CRP.     

Higher hydroxyurea adherence among young adults with sickle cell disease compared to children and adolescents

BackgroundSickle cell disease (SCD) results in severe complications, such as anaemia and pain episodes. Hydroxyurea (HU) is efficacious in SCD, yet adherence remains low.ObjectiveTo assess the relationship of HU adherence to health care utilization and patients’ characteristics.MethodsThis is a 5-year retrospective chart review. Patients’ demographics and medical history were collected from the electronic medical record (EMR). HU adherence was evaluated using foetal haemoglobin “HbF%”, mean corpuscular volume “MCV”, and absolute neutrophil count “ANC”. Age groups included children (<12 years), adolescents (12–17 years), and young adults (≥18 years).ResultsA total of 113 SCD patients on HU were included (median age 14 years, IQR 10–20; 50% female; 88% HbSS). Young adults had significantly higher HU adherence compared to adolescents and children, including higher median HbF% (24.2 vs. 12.4 vs. 8.6, p = .003), MCV (fl) (106.4 vs. 96.2 vs. 95.4, p = .01) and lower ANC (10³/ml) (3.25 vs. 4.9 vs. 4.2, p = .01), respectively. Patients with chronic pain had lower HU adherence (HbF% 15.3 vs. 10.7, p = .04; ANC 3.6 vs. 6.3, p = .002; MCV 102.3 vs. 93.1, p = .1). Patients with higher HbF or MCV and lower ANC had significantly less frequent emergency room visits (r_s=–0.26, p = .01; r_s=–0.23, p = .01; r_s=0.24, p = .01) and hospitalizations (r_s=–0.27, p = .01; r_s=–0.31, p = .01; r_s=0.21, p = .02) as well as shorter length of stays (r_s=–0.27, p = .0045; r_s=–.34, p = 0.004; r_s=0.23, p = .02), respectively. Similar trends in HU adherence and health care utilization were seen in subgroup analysis of only HbSS patients. There was no significant association of HU adherence to patients’ sex, socio-economic status, distance from hospital, and HU duration.ConclusionsYoung adults with SCD had significantly higher HU adherence compared to children and adolescents. Patients with lower HU adherence and/or chronic pain had increased health care utilization. Future studies examining barriers to adherence and evaluating interventions to optimize HU adherence in SCD are warranted.

KEY MESSAGES

1. Young adults with SCD had significantly higher HU adherence, as reflected in their laboratory markers, compared to children and adolescents.
2. Patients with higher HU adherence and/or those without chronic pain had lower or less frequent health care utilization.
3. No significant association of HU adherence to patients’ sex, socio-economic status and distance from hospital.

     

Realistic dielectric response of high temperature sintered ZnO ceramic: a microscopic and spectroscopic approach

High temperature sintering (1200–1400 °C) has been performed on ZnO ceramics. An X-ray Absorption Fine Structure (XAFS) study shows that high sintering temperature introduces a constant amount of V_O and V_Zn defects without any significant effect on the crystal or electronic structure of Wurtzite ZnO. The combined effects of grain boundaries and voids are considered responsible for the apparent colossal dielectric constant (ε′) > 10⁴ at low frequency (∼10² Hz) for all the sintered ZnO ceramics. The superior contact among grains of the ZnO-1200 sample enhances both the interfacial and orientational polarization of the Zn²⁺–V_O dipoles, which results in the increase of low and high frequency dielectric constants (ε′) and the corresponding dielectric loss (tan δ) also increases. On the other hand, high temperature sintering of ZnO at 1300 °C and 1400 °C introduces voids at the expense of reduced grain and grain boundary contact areas, thus affecting both the interfacial and orientational polarization with corresponding reduction of dielectric constant (ε′) and dielectric loss. Orientational polarizations due to Zn²⁺–V_O dipoles are suggested to remain fixed and it is the microstructure which controls the dielectric properties of high temperature sintered ZnO ceramics.

Superior grain contacts of ZnO-1200 samples enhance low and high frequency dielectric constants (ε′) and dielectric loss (tan δ).