Poly(Sitosterol)-Based Hydrophobic Blocks in Amphiphilic Block Copolymers for the Assembly of Hybrid Vesicles.

Amphiphilic block copolymer and lipids can be assembled into hybrid vesicles (HVs), which are an alternative to liposomes and polymersomes. Block copolymers that have either poly(sitostryl methacrylate) or statistical copolymers of sitosteryl methacrylate and butyl methacrylate as the hydrophobic part and a poly(carboxyethyl acrylate) hydrophilic segment are synthesized and characterized. These block copolymers assemble into small HVs with soybean L-α-phosphatidylcholine (soyPC), confirmed by electron microscopy and small-angle X-ray scattering. The membrane's hybrid nature is illustrated by fluorescence resonance energy transfer between labeled building blocks. The membrane packing, derived from spectra when using Laurdan as an environmentally sensitive fluorescent probe, is comparable between small HVs and the corresponding liposomes with molecular sitosterol, although the former show indications of transmembrane asymmetry. Giant HVs with homogenous distribution of the block copolymers and soyPC in their membranes are assembled using the electroformation method. The lateral diffusion of both building blocks is slowed down in giant HVs with higher block copolymer content, but their permeability toward (6)-carboxy-X-rhodamine is higher compared to giant vesicles made of soyPC and molecular sitosterol. This fundamental effort contributes to the rapidly expanding understanding of the integration of natural membrane constituents with designed synthetic compounds to form hybrid membranes.

Measuring narrative identity: rater coding versus questionnaire-based approaches.

Narrative identity - how individuals narrate their lived and remembered past - is usually assessed via independent rater coding, but new methods relying on self-report have been introduced. To test the assumption that different methods assess aspects of the same underlying construct, studies measuring similar components of narrative identity with different methods are needed. However, such studies are surprisingly rare. To begin to fill this gap, the present study compared the narrative variables, temporal coherence, causal coherence, and thematic coherence, measured via rater coding of participants' self-generated narratives of the remembered past and via subscales of the self-report measure Awareness of Narrative Identity Questionnaire (ANIQ). The results showed that the ANIQ subscales did not correlate significantly with their corresponding rater-coded dimension, and that the ANIQ subscales were generally unrelated to the other rater-coded dimensions. Furthermore, an exploratory factor analysis demonstrated that the ANIQ subscales loaded together on a factor that did not include any rater-coded variables. The findings suggest that the narrative variables share little empirical overlap when assessed via the ANIQ and rater coding of self-generated narratives.

Narrative identity does not predict well-being when controlling for emotional valence.

Narrative identity refers to a person's internalized and evolving life story. It is a rapidly growing research field, motivated by studies showing a unique association with well-being. Here we show that this association disappears when controlling for the emotional valence of the stories told and individuals' general experience of autobiographical memory. Participants (N = 235) wrote their life story and completed questionnaires on their general experience of autobiographical memory and several dimensions of well-being and affect. Participants' life stories were coded for standard narrative identity variables, including agency and communion. When controlling for emotional valence of the life story, the general experience of autobiographical memory was a significant predictor of most well-being measures, whereas agency was a predictor of one variable only and communion of none. These findings contradict the claim of an incremental association between narrative identity and well-being, and have important theoretical and practical implications for narrative identity as an outcome measure in interventions.

The reconstructive nature of involuntary autobiographical memories.

Influential clinical theories propose that parts of traumatic or stressful events are stored in an unprocessed, purely perceptual form, which is inaccessible for voluntary retrieval but may spontaneously return to consciousness involuntarily in response to matching cues. This leads to perceptually vivid, and largely veridical involuntary memories of the traumatic scene, remembered with the original emotions and from the same vantage point as during the event. Several lines of evidence contradict this position. First, involuntary memories are not more veridical than memories retrieved deliberately. Second, involuntary memories for trauma-related events are not more frequently remembered with the original first-person perspective, and individuals with PTSD do not report more first-person involuntary memories than individuals without PTSD. Third, involuntary memories of stressful moments that are subjectively experienced as repetitive do not come to mind in a fixed and unchangeable form. Fourth, involuntary memories do not have privileged access to the most emotional moments (so-called hotspots) of a stressful event and the content and choice of hotspots change over time. Fourth, although involuntary memories are associated with enhanced emotional impact, this does not imply reactivation of the original emotion. We conclude that involuntary memories, although effortless, are products of (re)constructive processes.

On-Site Measurement of Fat and Protein Contents in Milk Using Mobile NMR Technology.

Robust and easy-to-use NMR sensor technology is proposed for accurate, on-site determination of fat and protein contents in milk. The two parameters are determined using fast consecutive 1H and 35Cl low-field NMR experiments on milk samples upon the 1:1 addition of a low-cost contrast solution. Reliable and accurate measurements are obtained without tedious calibrations and the need for extensive database information and may readily be conducted by non-experts in production site environments. This enables on-site application at farms or dairies, or use in laboratories harvesting significant reductions in costs and time per analysis as compared to wet-chemistry analysis. The performance is demonstrated for calibration samples, various supermarket milk products, and raw milk samples, of which some were analyzed directly in the milking room. To illustrate the wide application range, the supermarket milk products included both conventionally/organically produced, lactose-free milk, cow's, sheep's and goat's milk, homogenized and unhomogenized milk, and a broad nutrient range (0.1-9% fat, 1-6% protein). Excellent agreement between NMR measurements and reference values, without corrections or changes in calibration for various products and during extensive periods of experiment conduction (4 months) demonstrates the robustness of the procedure and instrumentation. For the raw milk samples, correlations between NMR and IR, NMR and wet-chemistry, as well as IR and wet-chemistry results, show that NMR, in terms of accuracy, compares favorably with the other methods.

Implantable cardiac devices in adult patients with repaired tetralogy of Fallot.

OBJECTIVES: Implantable cardiac devices are common in patients with tetralogy of Fallot (ToF) (18.3-21.3%) according to previous reports from large centres. We conducted this study to investigate the prevalence and incidence of cardiac devices in a less selected population of patients with ToF and assess factors other than arrhythmia associated with having a device. Design: 530 adult (≥18 years) patients with repaired ToF were identified in the national registry of congenital heart disease (SWEDCON) and matched with data from the Swedish pacemaker registry. Patients with implantable cardiac devices were compared with patients without devices. Results: Seventy-five patients (14.2%) had a device; 51 (9.6%) had a pacemaker and 24 (4.5%) had an implantable cardioverter defibrillator. The incidence in adult age (≥18 years) was 5.9/1000 patient years. Estimated device free survival was 97.5% at twenty, 87.2% at forty and 63.5% at sixty years of age. Compared with previous studies, the prevalence of devices was lower, especially for ICD. In multivariate logistic regression, cardiovascular medication (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8-6.8), impaired left ventricular function, (OR 2.6, 95%CI 1.3-5.0) and age (OR 1.02, 95%CI 1.002-1.05) were associated with having a device. Conclusion: The prevalence of devices in our population, representing a multicenter register cohort, was lower than previously reported, especially regarding ICD. This can be due to differences in treatment traditions with regard to ICD in this population, but it may also be that previous studies have reported selected patients with more severe disease.

Through the gateway of the senses: investigating the influence of sensory modality-specific retrieval cues on involuntary episodic memory.

Involuntary memories are memories of past events that come to mind with no preceding attempts of retrieval. They typically arise in response to situational cues, but little is known as to how such cues modulate involuntary memories. Here, we examined how the sensory modality of the cues affects involuntary memory frequency and content. Participants watched first-person perspective films and were later presented with visuospatial and/or auditory cues from the films. We then assessed their experience of involuntary memories for other moments from the films. Across Experiments 1 and 2, visuospatial cues resulted in a greater frequency of involuntary memories, and produced memories with a higher proportion of visual content. In Experiment 3, this effect was replicated using a more auditorily engaging film and occurred whether participants focused on the film's auditory or visual components, but was more pronounced when there was a match between encoding fixation and the retrieval cue. These findings suggest that visuospatial cues may outshine auditory cues in terms of involuntary memory elicitation and content.

High prevalence of ascending aortic dilation in adults with repaired coarctation of the aorta.

BACKGROUND: Ascending aortic dilation is a feared complication in adults with repaired coarctation of the aorta, as the condition is associated with life-threatening complications such as aortic dissection and rupture. However, the data are currently limited regarding factors associated with ascending aortic dilation in these patients. METHODS AND RESULTS: From the national register of congenital heart disease, 165 adult patients (≥ 18 years old) with repaired coarctation of the aorta, and echocardiographic data on aortic dimensions, were identified (61.2% male, mean age 35.8 ± 14.5 years). Aortic dilation (aortic diameters > 2 SD above reference mean) was found in 55 (33.3%) of the 165 included patients, and was associated with manifest aortic valve disease in univariable logistic regression analysis (OR 2.44, 95% CI [1.23, 4.83]). CONCLUSIONS: Aortic dilation is common post-repair of coarctation of the aorta, and is associated with manifest aortic valve disease and thus indirectly with the presence of a bicuspid aortic valve. However, no association was found between aortic dilation and age or blood pressure.

Risk factors for permanent pacemaker implantation in patients receiving a balloon-expandable transcatheter aortic valve prosthesis.

Permanent pacemaker implantation (PPI) is a widely recognized complication associated with TAVI (incidence up to 20%). Smaller registries have identified several variables associated with PPI. The objective was to validate patient- and transcatheter aortic valve implantation (TAVI)-related procedural variables associated with PPI. We performed a retrospective analysis of patients from six European centers undergoing TAVI with the Edwards SAPIEN 3 prosthesis. Baseline variables and pre-procedural ECG characteristics and CT-scans were taken into account. Data for 1745 patients were collected; 191 (10.9%) required PPI after TAVI. The baseline variables pulmonary hypertension (OR 1.64; 95% CI 1.01-2.59), QRS duration > 117 ms (OR 2.58; 95% CI 1.73-3.84), right bundle branch block (RBBB; OR 5.14; 95% CI 3.39-7.72), left anterior hemi block (OR 1.92; 95% CI 1.19-3.02) and first-degree atrioventricular block (AVB, OR 1.63; 95%CI 1.05-2.46) were significantly associated with PPI. RBBB (OR 8.11; 95% CI 3.19-21.86) and first-degree AVB (OR 2.39; 95% CI 1.18-4.66) remained significantly associated in a multivariate analysis. Procedure-related variables included access site (TF; OR 1.97; 95% CI 1.07-4.05), implanted valve size (29 mm; OR 1.88; 95% CI 1.35-2.59), mean TAVI valve implantation depth below the annulus > 30% (OR 3.75; 95% CI 2.01-6.98). Patients receiving PPI had longer ICU stays and later discharges. Acute kidney injury stage 2/3 was more common in patients with PPI until discharge (15.2 vs. 3.1%; p = 0.007), but was not statistically significant thereafter. Further differences in outcomes at 30 days did not reach significance. The data will aid pre- and post-procedural patient management and prevent adverse long-term outcomes.Clinical Trial: NCT03497611.

Peripheral nerve blocks for analgesia after elective total hip arthroplasty.

A significant subgroup of patients suffer from moderate or severe pain after total hip arthroplasty (THA). Regional analgesia has the potential to reduce post-operative pain and thereby spare patients from opioids, but regional analgesia of the hip is complicated as the area is innervated by multiple nerves. However, the nociceptors of the hip joint are primarily innervated by the obturator and femoral nerves. The effect of an obturator nerve block (ONB) on pain following THA has never been investigated. A femoral nerve block is known to reduce pain after THA, but is unfortunately accompanied by an increased risk of fall. We have developed a novel nerve block-the iliopsoas plane block (IPB)-that has the potential to anaesthetize the hip articular sensory branches of the femoral nerve without causing motor blockade.

An iliopsoas plane block does not cause motor blockade-A blinded randomized volunteer trial.

BACKGROUND: A femoral nerve block relieves pain after total hip arthroplasty, but its use is controversial due to motor paralysis accompanied by an increased risk of fall. Assumedly, the iliopsoas plane block (IPB) targets the hip articular branches of the femoral nerve without motor blockade. However, this has only been indicated in a cadaver study. Therefore, we designed this volunteer study. METHODS: Twenty healthy volunteers were randomly allocated to blinded paired active vs. sham IPB (5 mL lidocaine 18 mg/mL with epinephrine vs saline). The primary outcome was reduction of maximal force of knee extension after IPB compared to baseline. Secondary outcomes included reduction of maximal force of hip adduction, and the pattern of injectate spread assessed with magnetic resonance imaging. RESULTS: Mean (confidence interval) change of maximal force of knee extension from baseline to after IPB was -9.7 N (-22, 3.0) (P = .12) (n = 14). The injectate was consistently observed in an anatomically well-defined closed fascial compartment between the intra- and extra-pelvic components of the iliopsoas muscle anterior to the hip joint. CONCLUSION: We observed no significant reduction of maximal force of knee extension after an IPB. The injectate was contained in a fascial compartment previously shown to contain all sensory branches from the femoral nerve to the hip joint. The clinical consequence of selective anesthesia of all sensory femoral nerve branches from the hip could be a reduced risk of fall compared to a traditional femoral nerve block. Registration of Trial: The trial was prospectively registered in EudraCT (Reference: 2018-000089-12, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-000089-12).

PD-L1 in squamous cell carcinoma of the oral tongue shows gender-specific association with prognosis.

OBJECTIVE: To use alternative quantitation approaches to clarify the clinical implication of programmed cell death ligand 1 (PD-L1) in squamous cell carcinoma of the oral tongue (SCCOT). MATERIALS AND METHODS: Ventana SP263 immunohistochemistry assay and a multiplicative QuickScore method were applied to quantify PD-L1 in tumor and surrounding immune cells from 101 patients with SCCOT. Tumor-infiltrating immune cells were estimated from bulk tissue transcriptional profiles of 25 patients. Circulating PD-L1 levels were measured in serum from 30 patients using an electrochemiluminescence assay platform. RESULTS: We found higher tumor cell PD-L1 levels in females than males (p = .019). For patients with low PD-L1 in tumor cells, better survival was seen in males than females (overall survival p = .021, disease-free survival p = .020). Tumor-infiltrating natural killer T cells, immature dendritic cells, and M1 macrophages were positively associated with tumor cell PD-L1 (p < .05). CONCLUSIONS: Our data confirmed the significance of gender on tumor cell PD-L1 expression and demonstrated combined effects of gender and PD-L1 levels on clinical outcome in patients with SCCOT. The data also indicated the involvement of specific immune cell types in PD-L1-regulated immune evasion.

Differentiating depression and ADHD without depression in adults with processing-speed measures.

OBJECTIVE: We evaluated processing-speed and shift-cost measures in adults with depression or attention-deficit hyperactivity disorder (ADHD) and monitored the effects of treatment. We hypothesised that cognitive-speed and shift-cost measures might differentiate diagnostic groups. METHODS: Colour, form, and colour-form stimuli were used to measure naming times. The shift costs were calculated as colour-form-naming time minus the sum of colour- and form-naming times. Measurements were done at baseline and end point for 42 adults with depression and 42 with ADHD without depression. Patients with depression were treated with transcranial pulsed electromagnetic fields and patients with ADHD with methylphenidate immediate release. RESULTS: During depression treatment, reductions in naming times were recorded weekly. One-way analysis of variance indicated statistical between-group differences, with effect sizes in the medium range for form and colour-form. In both groups, naming times were longer before than after treatment. For the ADHD group, shift costs exceeded the average-normal range at baseline but were in the average-normal range after stabilisation with stimulant medication. For the depression group, shift costs were in the average-normal range at baseline and after treatment. Baseline colour-form-naming times predicted reductions in naming times for both groups, with the largest effect size and index of forecasting efficiency for the ADHD group. CONCLUSIONS: The cognitive-processing-speed (colour-form) and shift-cost measures before treatment proved most sensitive in differentiating patients with depression and ADHD. Reductions in naming times for the depression group were suggested to reflect improved psychomotor skills rather than improved cognitive control.

Methanol-Assisted Autocatalysis in Catalytic Methanol Synthesis.

Catalytic methanol synthesis is one of the major processes in the chemical industry and may grow in importance, as methanol produced from CO2 and sustainably derived H2 are envisioned to play an important role as energy carriers in a future low-CO2 -emission society. However, despite the widespread use, the reaction mechanism and the nature of the active sites are not fully understood. Here we report that methanol synthesis at commercially applied conditions using the industrial Cu/ZnO/Al2 O3 catalyst is dominated by a methanol-assisted autocatalytic reaction mechanism. We propose that the presence of methanol enables the hydrogenation of surface formate via methyl formate. Autocatalytic acceleration of the reaction is also observed for Cu supported on SiO2 although with low absolute activity, but not for Cu/Al2 O3 catalysts. The results illustrate an important example of autocatalysis in heterogeneous catalysis and pave the way for further understanding, improvements, and process optimization of industrial methanol synthesis.

Cryogen-free dissolution dynamic nuclear polarization polarizer operating at 3.35 T, 6.70 T, and 10.1 T.

PURPOSE: A novel dissolution dynamic nuclear polarization (dDNP) polarizer platform is presented. The polarizer meets a number of key requirements for in vitro, preclinical, and clinical applications. METHOD: It uses no liquid cryogens, operates in continuous mode, accommodates a wide range of sample sizes up to and including those required for human studies, and is fully automated. RESULTS: It offers a wide operational window both in terms of magnetic field, up to 10.1 T, and temperature, from room temperature down to 1.3 K. The polarizer delivers a 13 C liquid state polarization for [1-13 C]pyruvate of 70%. The build-up time constant in the solid state is approximately 1200 s (20 minutes), allowing a sample throughput of at least one sample per hour including sample loading and dissolution. CONCLUSION: We confirm the previously reported strong field dependence in the range 3.35 to 6.7 T, but see no further increase in polarization when increasing the magnetic field strength to 10.1 T for [1-13 C]pyruvate and trityl. Using a custom dry magnet, cold head and recondensing, closed-cycle cooling system, combined with a modular DNP probe, and automation and fluid handling systems, we have designed a unique dDNP system with unrivalled flexibility and performance.

A unified heteronuclear decoupling picture in solid-state NMR under low radio-frequency amplitude and fast magic-angle-spinning frequency regime.

Heteronuclear spin decoupling is a highly important component of solid-state NMR experiments to remove undesired coupling interactions between unlike spins for spectral resolution. Recently, experiments using a unification strategy of standard decoupling schemes were presented for high radio-frequency (RF) amplitudes and slow-intermediate magic-angle-spinning (MAS) frequencies, in the pursuit of deeper understanding of spin decoupling under phase-modulated RF irradiation [A. Equbal et al., J. Chem. Phys. 142, 184201 (2015)]. The approach, unified two-pulse heteronuclear decoupling (UTPD), incorporates the simultaneous time- and phase-modulation strategies, commonly used in solid-state NMR. Here, the UTPD based decoupling scheme is extended to the experimentally increasingly important regime of low RF amplitudes and fast MAS frequencies. The unified decoupling approach becomes increasingly effective in identifying the deleterious dipole-dipole and, in particular, J recoupling conditions which become critical for the low-amplitude RF regime. This is because J coupling is isotropic and therefore not averaged out by sample spinning unlike the anisotropic dipole-dipole coupling. Numerical simulations and analytic theory are used to understand the effects of various nuclear spin interactions on the decoupling performance of UTPD, in particular, the crucial difference between the low-phase and high-phase UTPD conditions with respect to J coupling. In the UTPD scheme, when the cycle-frequency of the pulse-sequence is comparable to the RF nutation frequency, the existence of a non-zero effective rotation in the basic two-pulse scheme becomes an essential feature for the efficient and robust averaging out of the scalar J coupling. This broad viewpoint is expected to bring different optimum low-power decoupling pulse schemes under a common footing.

Methylphenidate effects on processing speed in a clinical sample of adults with ADHD and substance use disorder: a pilot study.

BACKGROUND: Substance use disorders (SUDs) are common comorbidities of Attention Deficit Hyperactivity Disorder (ADHD). The most commonly prescribed medication for ADHD is methylphenidate. The clinical response to methylphenidate may be monitored against DSM-5 symptomatology, rating scales or interviews. AIMS: To evaluate the use of perceptual and cognitive processing speed measures to monitor methylphenidate effects in adults with ADHD and SUD. METHODS: A Quick Test of Cognitive Speed (AQT) monitored perceptual and cognitive processing speed in 28 adults with ADHD and SUD on treatment with methylphenidate before and after the morning dose. RESULTS: Twenty-six patients responded on AQT after the morning dose of methylphenidate. One-way ANOVA indicated significant treatment effects for color, form, and color-form combination naming, but not for shift cost values. Before the morning dose of methylphenidate, 92% were identified by cutoff time criteria for longer-than-normal processing times. After the morning dose of methylphenidate, 65% obtained color and form measures in the normal range for age peers. Only 35% obtained color-form processing measures in the normal range. Inter-individual response variability before medication intake was considerably larger than previously reported in studies of adults with ADHD only. CONCLUSION: Proportionally, fewer adults with ADHD and SUD exhibited normalization of processing speed than previously observed for adults with ADHD without SUD. A potential clinical implication of the present study is that the AQT test may be used as a tool for dose-adjustment of central stimulants in the treatment of adults with ADHD and SUD.

Fast Wide-Line Solid-State NMR on a Low-Cost Benchtop Spectrometer.

Solid-state NMR may provide access to a wealth of information on molecular structure and dynamics. However, for many applications, the acquisition is challenged by broad resonances implying large spectral linewidths and low sensitivity. Conventionally, this is tackled by using costly and laboratory-fixed spectrometers based on large high-field superconducting magnets. In this Communication, we demonstrate that a range of challenging wide-line solid-state NMR spectra can be acquired on a robust, maintenance-free, low-cost benchtop/mobile NMR spectrometer with a sensitivity comparable to common high-field instruments. The performance and versatility for recording sensitive wide-line spectra is demonstrated through acquisition of 31 P NMR of paramagnetic FePO4 and full quadupolar lineshapes of Al2 O3 (27 Al) and KNO3 (14 N). Also, we introduce interleaved acquisition of frequency-stepped slices providing a dramatic reduction of the required experiment time.

Contact allergy in Danish children: Current trends.

BACKGROUND: Contact allergy is common in children, but may be underdiagnosed. Importantly, the clinical relevance of specific allergies is subject to constant change, and it is therefore important to continuously monitor the trends and changes of contact allergies in the paediatric population. OBJECTIVES: To identify possible changes in contact allergy and allergic contact dermatitis among Danish children referred for patch testing. METHODS: A retrospective study was performed based on patch test data from the Danish National Database of Contact allergy. The current data were compared with previously published data on Danish children referred for patch testing. RESULTS: Between 2012 and 2016, 1573 children and adolescents were patch tested. Overall, 385 (24.5%) had at least 1 positive patch test reaction. The overall prevalence was similar in boys and girls, across age groups, and in patients with and without atopic dermatitis. Statistically significant increases in contact allergy to fragrances and isothiazoliones were seen, whereas a decrease in nickel allergy was found. CONCLUSION: Allergic contact dermatitis continues to be a common disease in children, and is even significantly increasing for some allergens.

Surgical management of outflow tract obstruction after transapical mitral valve implantation.

Left ventricular outflow tract (LVOT) obstruction due to systolic anterior motion of the anterior mitral valve leaflet (AML) is a known complication after mitral valve repair or transfemoral/transapical mitral valve implantation (TMVI). We present a patient with a previous mitral valve repair who developed LVOT obstruction after TMVI in whom the AML was surgically resected using a transaortic approach.