Nanofiber Ion-Selective Membrane-Coated Carbon Paper All-Solid-State Sensors: One Stone, Two Birds.

Potentiometric sensors with nanostructural ion-selective membranes were prepared and tested. Electrospun nanofiber mats were applied in novel all-solid-state sensors, using carbon paper as an electronically conducting support. For the sake of simplicity, application of a solid contact layer was avoided, and redox-active impurities naturally present in the carbon paper have proven to be effective as ion-to-electron transducers. Application of a nanostructural ion-selective membrane requires an innovative approach to combine the receptor layer with the support. The nanofiber mat portion was fused with carbon paper in a hot-melt process. Applying temperature close to 120 °C for a short time (3 s) allowed binding the nanostructural ion-selective membrane with carbon paper, without significant changes in the nanofiber structure. This process was conveniently performed together with the lamination of the carbon paper support. The thus obtained, potentially disposable sensors were characterized as exhibiting highly reproducible potential readings in time as well as between sensors belonging to the same batch. The benefits of the application of nanostructural ion-selective membranes include shorter equilibration time, lower detection limit, and significantly lower material consumption. However, the nanostructural membrane is characterized by a higher electrical resistance, which is attributed to higher porosity.

Multiparametric Prediction Models for Coronavirus Disease 2019 Vaccine Selection: Results of a Comparative Population-Based Cohort Study.

BACKGROUND: An understanding vaccine-dependent effects on protective and sustained humoral immune response is crucial to planning future vaccination strategies against coronavirus disease 2019 (COVID-19). METHODS: In this multicenter, population-based, cohort study including 4601 individuals after primary vaccination against COVID-19 ≥ 4 months earlier we compared factors associated with residual antibody levels against severe acute respiratory syndrome coronavirus-2 receptor-binding domain (RBD) across different vaccination strategies (BNT162b2, mRNA-1273, or ChAdOx1). RESULTS: Our main model including 3787 individuals (2 × BNT162b2, n = 2271; 2 × mRNA-1273, n = 251; 2 × ChAdOx1, n = 1265), predicted significantly lower levels of anti-RBD antibodies after 6 months in individuals vaccinated with ChAdOx1 (392.7 binding antibody units per milliliter [BAU/mL]) compared with those vaccinated with BNT162b2 (1179.5 BAU/mL) or mRNA-1273 (2098.2 BAU/mL). Vaccine-dependent association of antibody levels was found for age with a significant predicted difference in BAU/ml per year for BNT162b2 (-21.5; 95% confidence interval [CI], -24.7 to -18.3) and no significant association for mRNA-1273 (-4.0; 95% CI, -20.0 to 12.1) or ChAdOx1 (1.7; 95% CI, .2 to 3.1). The predicted decrease over time since full immunization was highest in mRNA-1273 (-23.4; 95% CI, -31.4 to -15.4) compared with BNT162b2 (-5.9; 95% CI, -7 to -4.8). CONCLUSIONS: Our study revealed population-based evidence of vaccine-dependent effects of age and time since full immunization on humoral immune response. Findings underline the importance of individualized vaccine selection, especially in elderly individuals.

Application of Monoferrocenylsumanenes Derived from Sonogashira Cross-Coupling or Click Chemistry Reactions in Highly Sensitive and Selective Cesium Cation Electrochemical Sensors.

This paper reports the synthesis and characterization of novel monoferrocenylsumanenes obtained by means of the Sonogashira cross-coupling or click chemistry reaction as well as their application in cesium cation electrochemical sensors. A new synthetic protocol based on Sonogashira cross-coupling was developed for the synthesis of monoferrocenylsumanene or ethynylsumanene. The click chemistry reaction was introduced to the sumanene chemistry through the synthesis of 1,2,3-triazole containing monoferrocenylsumanene. The designed synthetic methods for the modification of sumanene at the aromatic position proved to be efficient and proceeded under mild conditions. The synthesized sumanene derivatives were characterized by detailed spectroscopic analyses of the synthesized sumanene derivatives. The supramolecular interactions between cesium cations and the synthesized monoferrocenylsumanenes were spectroscopically and electrochemically investigated. Furthermore, the design of the highly selective and sensitive cesium cation fluorescence and electrochemical sensors comprising the synthesized monoferrocenylsumanenes as receptor compounds was analyzed. The tested cesium cation electrochemical sensors showed excellent limit of detection values in the range of 6.0-9.0 nM. In addition, the interactions between the synthesized monoferrocenylsumanenes and cesium cations were highly selective, which was confirmed by emission spectroscopy, laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), and cyclic voltammetry.

Counterion-controlled phase equilibria in a charge-regulated polymer solution.

We study phase equilibria in a minimal model of charge-regulated polymer solutions. Our model consists of a single polymer species whose charge state arises from protonation-deprotonation processes in the presence of a dissolved acid, whose anions serve as screening counterions. We explicitly account for variability in the polymers' charge states. Homogeneous equilibria in this model system are characterised by the total concentration of polymers, the concentration of counter-ions and the charge distributions of polymers which can be computed with the help of analytical approximations. We use these analytical results to characterise how parameter values and solution acidity influence equilibrium charge distributions and identify for which regimes uni-modal and multi-modal charge distributions arise. We then study the interplay between charge regulation, solution acidity and phase separation. We find that charge regulation has a significant impact on polymer solubility and allows for non-linear responses to the solution acidity: Re-entrant phase behaviour is possible in response to increasing solution acidity. Moreover, we show that phase separation can yield to the coexistence of local environments characterised by different charge distributions.

Signatures of slip in dewetting polymer films.

Thin polymer films on hydrophobic substrates are susceptible to rupture and hole formation. This, in turn, initiates a complex dewetting process, which ultimately leads to characteristic droplet patterns. Experimental and theoretical studies suggest that the type of droplet pattern depends on the specific interfacial condition between the polymer and the substrate. Predicting the morphological evolution over long timescales and on the different length scales involved is a major computational challenge. In this study, a highly adaptive numerical scheme is presented, which allows for following the dewetting process deep into the nonlinear regime of the model equations and captures the complex dynamics, including the shedding of droplets. In addition, our numerical results predict the previously unknown shedding of satellite droplets during the destabilization of liquid ridges that form during the late stages of the dewetting process. While the formation of satellite droplets is well known in the context of elongating fluid filaments and jets, we show here that, for dewetting liquid ridges, this property can be dramatically altered by the interfacial condition between polymer and substrate, namely slip. This work shows how dissipative processes can be used to systematically tune the formation of patterns.

Successful application of pulsed electromagnetic fields in a patient with post-COVID-19 fatigue: a case report.

BACKGROUND: Post-COVID-19 fatigue is a frequent symptom in COVID-19 survivors, which substantially limits patients to achieve full recovery and potentially restrains return to work. The previous literature has not yet reported the use of pulsed electromagnetic fields in this indication. METHODS: Over the course of 5 weeks, 10 sessions of pulsed electromagnetic field treatment with a high magnetic flux density were applied to a patient suffering from post-COVID-19 fatigue syndrome. Fatigue, work ability, quality of life as well as anxiety, depression, stress level, and resilience were evaluated using validated patient-reported outcome measures. RESULTS: Fatigue, work ability, quality of life, and psychological well-being improved clearly over the course of the treatment and showed stable results 6 weeks later. CONCLUSION: The use of pulsed electromagnetic field therapy with a device that allows sufficient penetration of the body tissue might be a promising physical modality to manage post-COVID-19 fatigue syndrome, which could reduce clinical and economic health consequences. Clinical sham-controlled studies are needed to evaluate the effect of pulsed electromagnetic fields in this indication.

Tracking of Glycans Structure and Metallomics Profiles in BRAF Mutated Melanoma Cells Treated with Vemurafenib.

Nearly half of patients with advanced and metastatic melanomas harbor a BRAF mutation. Vemurafenib (VEM), a BRAF inhibitor, is used to treat such patients, however, responses to VEM are very short-lived due to intrinsic, adaptive and/or acquired resistance. In this context, we present the action of the B-Raf serine-threonine protein kinase inhibitor (vemurafenib) on the glycans structure and metallomics profiles in melanoma cells without (MeWo) and with (G-361) BRAF mutations. The studies were performed using α1-acid glycoprotein (AGP), a well-known acute-phase protein, and concanavalin A (Con A), which served as the model receptor. The detection of changes in the structure of glycans can be successfully carried out based on the frequency shifts and the charge transfer resistance after interaction of AGP with Con A in different VEM treatments using QCM-D and EIS measurements. These changes were also proved based on the cell ultrastructure examined by TEM and SEM. The LA-ICP-MS studies provided details on the metallomics profile in melanoma cells treated with and without VEM. The studies evidence that vemurafenib modifies the glycans structures and metallomics profile in melanoma cells harboring BRAF mutation that can be further implied in the resistance phenomenon. Therefore, our data opens a new avenue for further studies in the short-term addressing novel targets that hopefully can be used to improve the therapeutic regiment in advanced melanoma patients. The innovating potential of this study is fully credible and has a real impact on the global patient society suffering from advanced and metastatic melanomas.

The effect of resistance exercise on strength and safety outcome for people with haemophilia: A systematic review.

INTRODUCTION: Haemophilia is a congenital bleeding disorder with severe musculoskeletal complications. Resistance exercise is important to increase joint stability and to improve physical performance. AIM: This review aimed to investigate the safety and efficacy of resistance exercise interventions on people with haemophilia (PwH) and evaluate whether the American College of Sports Medicine resistance exercise criteria for healthy adults are valid for this population. METHODS: A systematic search in literature was conducted, using the databases PubMed, MEDLiNE, CINAHL, SCOPUS, PEDro and Cochrane Library. Out of 2.440 studies published between 1960 and November 2019, 14 studies (9 randomized controlled trials, 1 controlled trial, 4 single-group prospective studies) applying resistance exercise in juvenile and adult PwH corresponded to the inclusion criteria. RESULTS: Studies performed dynamic, isokinetic or a combination of isometric and dynamic resistance training. Most interventions were carried out in the context of a multimodal training. Resistance was provided using fixed and free weights, body weight, resistance bands and water resistance. Study protocols included clinical and home-based settings. Several studies suggest that training intensities lower than those known to increase the strength of healthy people are effective in increasing the strength of PwH. Resistance exercise seems to be a safe intervention if it is adequately monitored, individually adapted and applied with sufficient factor therapy. Due to the heterogeneity of study designs, training interventions and outcome measures a meta-analysis could not be performed. CONCLUSIONS: Further studies of higher methodological quality are needed to determine the optimal types of exercise, optimal dosage and timing.

Workplace injury rates and firm-level turnover in Montana's oil and gas industry.

BACKGROUND: Do workers follow their self-interest by minimizing injury risk in their employment decision? If so, employers could use injury reduction as a recruitment and retention strategy. This study explores whether injury incidence is associated with turnover in Montana's Oil and Gas industry. METHODS: A panel data set of Unemployment Insurance and Workers' Compensation administrative records from 2010 to 2015 was used to model the relationship between turnover and injury claim rates at the firm level. RESULTS: Total turnover and injury rates were found to be positively related while injury rates and separation rates had no such association. Quarters in which the employer experienced a severe injury had a 3.3 percentage point increase in separation rates. DISCUSSION: The findings suggest that injured workers contribute to increased turnover, but coworker turnover does not increase with increased injury rates in the firm. Secondary findings suggest a relationship between recent hires and increased injury rates, although further investigation is required.

Increased microcirculation detected by dynamic contrast-enhanced magnetic resonance imaging is of prognostic significance in asymptomatic myeloma.

This prospective study aimed to investigate the prognostic significance of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) as a non-invasive imaging technique delivering the quantitative parameters amplitude A (reflecting blood volume) and exchange rate constant kep (reflecting vascular permeability) in patients with asymptomatic monoclonal plasma cell diseases. We analysed DCE-MRI parameters in 33 healthy controls and 148 patients with monoclonal gammopathy of undetermined significance (MGUS) or smouldering multiple myeloma (SMM) according to the 2003 IMWG guidelines. All individuals underwent standardized DCE-MRI of the lumbar spine. Regions of interest were drawn manually on T1-weighted images encompassing the bone marrow of each of the 5 lumbar vertebrae sparing the vertebral vessel. Prognostic significance for median of amplitude A (univariate: P < 0·001, hazard ratio (HR) 2·42, multivariate P = 0·02, HR 2·7) and exchange rate constant kep (univariate P = 0·03, HR 1·92, multivariate P = 0·46, HR 1·5) for time to progression of 79 patients with SMM was found. Patients with amplitude A above the optimal cut-off point of 0·89 arbitrary units had a 2-year progression rate into symptomatic disease of 80%. In conclusion, DCE-MRI parameters are of prognostic significance for time to progression in patients with SMM but not in individuals with MGUS.

Association between magnetic resonance imaging patterns and baseline disease features in multiple myeloma: analyzing surrogates of tumour mass and biology.

OBJECTIVE: To assess associations between bone marrow infiltration patterns and localization in magnetic resonance imaging (MRI) and baseline clinical/prognostic parameters in multiple myeloma (MM). METHODS: We compared baseline MM parameters, MRI patterns and localization of focal lesions to the mineralized bone in 206 newly diagnosed MM patients. RESULTS: A high tumour mass (represented by International Staging System stage III) was significantly associated with severe diffuse infiltration (p = 0.015) and a higher number of focal lesions (p = 0.006). Elevated creatinine (p = 0.003), anaemia (p < 0.001) and high LDH (p = 0.001) correlated with severe diffuse infiltration. A salt and pepper diffuse pattern had a favourable prognosis. A higher degree of destruction of mineralized bone (assessed by X-ray or computed tomography) was associated with an increasing number of focal lesions on MRI (p < 0.001). Adverse cytogenetics (del17p/gain1q21/t(4;14)) were associated with diffuse infiltration (p = 0.008). The presence of intraosseous focal lesions exceeding the mineralized bone had a borderline significant impact on prognosis. CONCLUSIONS: Diffuse bone marrow infiltration on MRI correlates with adverse cytogenetics, lowered haemoglobin values and high tumour burden in newly diagnosed MM whereas an increasing number of focal lesions correlates with a higher degree of bone destruction. Focal lesions exceeding the cortical bone did not adversely affect the prognosis. KEY POINTS: • Diffuse MRI correlates with adverse cytogenetics, lowered haemoglobin and high tumour burden. • Higher numbers of MRI focal lesions correlate with increasing degree of bone destruction. • Focal lesions exceeding the cortical bone borderline significantly influence survival. • Moderate/severe diffuse infiltration and more than 23 focal lesions adversely affect survival.

Prognostic significance of increased bone marrow microcirculation in newly diagnosed multiple myeloma: results of a prospective DCE-MRI study.

OBJECTIVES: Aim of this prospective study was to investigate prognostic significance of increased bone marrow microcirculation as detected by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for survival and local complications in patients with multiple myeloma (MM). METHODS: We performed DCE-MRI of the lumbar spine in 131 patients with newly diagnosed MM and analysed data according to the Brix model to acquire amplitude A and exchange rate constant kep. In 61 patients a second MRI performed after therapy was evaluated to assess changes in vertebral height and identify vertebral fractures. RESULTS: Correlation analysis revealed significant positive association between beta2-microglobulin as well as immunoparesis with DCE-MRI parameters A and kep. Additionally, A was negatively correlated with haemoglobin levels and kep was positively correlated with LDH levels. Higher baseline kep values were associated with decreased vertebral height in a second MRI (P = 0.007) and A values were associated with new vertebral fractures in the lower lumbar spine (P = 0.03 for L4). Pre-existing lytic bone lesions or remission after therapy had no impact on the occurrence of vertebral fractures. Multivariate analysis revealed that amplitude A is an independent adverse risk factor for overall survival. CONCLUSION: DCE-MRI is a non-invasive tool with significance for systemic prognosis and vertebral complications. KEY POINTS: • Qualitative parameters from DCE-MRI are correlated with established factors of disease activity • Increased marrow microcirculation might be a risk factor for loss of vertebral height and fractures • Amplitude A is an independent predictor for shortened overall survival.

Ankle Movements During Supine Kicking in Infants Born Preterm.

BACKGROUND: Knowledge of musculoskeletal factors that influence supine kicking of infants born preterm has implications for early intervention. HYPOTHESES: Differences exist between infants born preterm and full-term in ankle kinematics during supine kicking, which are attributable to passive measures of the gastrocnemius/soleus (g/s) muscle tendon unit (MTU). SUBJECTS: Twenty infants born full-term and 22 born preterm were measured at term, 6 weeks, and 12 weeks of age. OUTCOME MEASURES: Ankle kinematics during supine kicking and g/s MTU length. RESULTS: Infants born preterm demonstrated less dorsiflexion, more plantar flexion, and more total ankle range during supine kicking. Gestational age explained 69% to 85% of the variability in MTU length from term to 12 weeks of age. MTU lengths explained 0% to 42% of the variance in ankle kinematics. CONCLUSIONS: Passive measures of the g/s MTU may inform clinicians about ankle kinematics in newborns to 12-week infants during supine kicking.

A magnetic resonance imaging-based prognostic scoring system to predict outcome in transplant-eligible patients with multiple myeloma.

Diffuse and focal bone marrow infiltration patterns detected by magnetic resonance imaging have been shown to be of prognostic significance in all stages of monoclonal plasma cell disorders and have, therefore, been incorporated into the definition of the disease. The aim of this retrospective analysis was to develop a rapidly evaluable prognostic scoring system, incorporating the most significant information acquired from magnetic resonance imaging. Therefore, the impact of bone marrow infiltration patterns on progression-free and overall survival in 161 transplant-eligible myeloma patients was evaluated. Compared to salt and pepper/minimal diffuse infiltration, moderate/severe diffuse infiltration had a negative prognostic impact on both progression-free survival (P<0.001) and overall survival (P=0.003). More than 25 focal lesions on whole-body magnetic resonance imaging or more than seven on axial magnetic resonance imaging were associated with an adverse prognosis (progression-free survival: P=0.001/0.003 and overall survival: P=0.04/0.02). A magnetic resonance imaging-based prognostic scoring system, combining grouped diffuse and focal infiltration patterns, was formulated and is applicable to whole-body as well as axial magnetic resonance imaging. The score identified high-risk patients with median progression-free and overall survival of 23.4 and 55.9 months, respectively (whole-body-based). Multivariate analyses demonstrated that the magnetic resonance imaging-based prognostic score stage III (high-risk) and adverse cytogenetics are independent prognostic factors for both progression-free and overall survival (whole-body-based, progression-free survival: hazard ratio=3.65, P<0.001; overall survival: hazard ratio=5.19, P=0.005). In conclusion, we suggest a magnetic resonance imaging-based prognostic scoring system which is a robust, easy to assess and interpret parameter summarizing significant magnetic resonance imaging findings in transplant-eligible patients with multiple myeloma.

Assembling Paramagnetic Ceruloplasmin at Electrode Surfaces Covered with Ferromagnetic Nanoparticles. Scanning Electrochemical Microscopy in the Presence of a Magnetic Field.

Adsorption of ceruloplasmin (Cp) at a gold electrode modified with ferromagnetic iron nanoparticles encapsulated in carbon (Fe@C Nps) leads to a successful immobilization of the enzyme in its electroactive form. The proper placement of Cp at the electrode surface on top of the nanocapsules containing an iron core allowed a preorientation of the enzyme, hence allowing direct electron transfer between the electrode and the enzyme. Laser ablation coupled with inductively coupled plasma mass spectrometry indicated that Cp was predominantly located at the paramagnetic nanoparticles. Scanning electrochemical microscopy measurements in the sample-generation/tip-collection mode proved that Cp was ferrooxidative inactive if it was immobilized on the bare gold surface and reached the highest activity if it was adsorbed on Fe@C Nps in the presence of a magnetic field.

Influence of slip on the Rayleigh-Plateau rim instability in dewetting viscous films.

A dewetting viscous film develops a characteristic fluid rim at its receding edge due to mass conservation. In the course of the dewetting process, the rim becomes unstable via an instability of Rayleigh-Plateau type. An important difference exists between this classic instability of a liquid column and the rim instability in a thin film as the growth of the rim is continuously fueled by the receding film. We explain how the development and macroscopic morphology of the rim instability are controlled by the slip of the film on the substrate. A single thin-film model captures quantitatively the characteristics of the complete evolution of the rim observed in the experiments.

Autoimmune and paraneoplastic seizures.

Seizures are a common feature of autoimmune encephalitis and are especially prevalent in patients with the commonest autoantibodies, against LGI1, CASPR2 and the NMDA, GABAB, and GABAA receptors. In this chapter, we discuss the classification, clinical, investigation, and treatment aspects of patients with these, and other autoantibody-mediated and -associated, illnesses. We highlight distinctive and common seizure semiologies which, often alongside other features we outline, can help the clinical diagnosis of an autoantibody-associated syndrome. Next, we classify these syndromes by either focusing on whether they represent underlying causative autoantibodies or T-cell-mediated syndromes and on the distinction between acute symptomatic seizures and a more enduring tendency to autoimmune-associated epilepsy, a practical and valuable distinction for both patients and clinicians which relates to the pathogenesis. We emphasize the more effective immunotherapy response in patients with causative autoantibodies, and discuss the emerging evidence for various first-, second-, and third-line immunotherapies. Finally, we highlight available clinical rating scales which can guide autoantibody testing and immunotherapy in patients with seizures of unknown etiology. Throughout, we relate the clinical and therapeutic observations to the immunobiology and neuroscience which drive these seizures.

Finding a perfect match of ion-exchanger and plasticizer for ion-selective sensors.

Application of neutral ionophore based ion-selective sensors requires presence of ion-exchanger in the receptor phase, silently assuming that it is not only soluble but also dissociates to ions in the applied plasticizer. Although for typically applied ion-selective membrane constituents (plasticizers - ion-exchanger pairs) dissociation of ion-exchangers to ions is proven by theoretical (or close to) performance of resulting sensors, search for alternative plasticizers or ion-exchangers requires a method allowing estimation of the match of properties of involved compounds. In this work we propose a simple optical approach allowing estimation of ion-exchanger interactions with plasticizer. The results were confirmed by conductivity studies of model plasticizers solutions. The estimated dissociation constants of model ion-exchangers in plasticizers used are in excellent agreement with the results of optical studies. It was shown that solubility coupled with poor dissociation to ions of ion-exchanger affects performance of the resulting ion-selective membrane. Rational choice of properties of ion-exchanger and plasticizer allows finding a perfect match of the two, that results in improvements in performance of sensors (e.g. detection limits). As model sensors potassium and sodium ion-selective electrodes with poly(vinyl chloride) (PVC) based membranes, plasticized with classical plasticizer bis(2-ethylhexyl sebacate) or biodegradable alternative acetyl tributyl citrate, were prepared and studied using selected ion-exchangers.

Metal leakage from orthodontic appliances chemically alters enamel surface during experimental in vitro simulated treatment.

Human enamel is composed mainly of apatite. This mineral of sorption properties is susceptible to chemical changes, which in turn affect its resistance to dissolution. This study aimed to investigate whether metal leakage from orthodontic appliances chemically alters the enamel surface during an in vitro simulated orthodontic treatment. Totally 107 human enamel samples were subjected to the simulation involving metal appliances and cyclic pH fluctuations over a period of 12 months in four complimentary experiments. The average concentrations and distribution of Fe, Cr, Ni, Ti and Cu within the enamel before and after the experiments were examined using ICP‒MS and LA‒ICP‒MS techniques. The samples exposed to the interaction with metal appliances exhibited a significant increase in average Fe, Cr and Ni (Kruskal-Wallis, p < 0.002) content in comparison to the control group. The outer layer, narrow fissures and points of contact with the metal components showed increased concentrations of Fe, Ti, Ni and Cr after simulated treatment, conversely to the enamel sealed with an adhesive system. It has been concluded that metal leakage from orthodontic appliances chemically alters enamel surface and microlesions during experimental in vitro simulated treatment.

[Treatment of haemophilia in Austria]. / Hämophilie-Behandlung in Österreich.

This guideline is intended to provide practical guidance for the diagnosis and treatment of haemophilia in Austria. Few randomized controlled interventional trials are available addressing the treatment of haemophilia, therefore recommendations are usually based on low level of evidence and represent expert consensus.This guideline is based on the WFH guideline, published in 2020, and adapted according to the national circumstances and experience.It includes recommendations and suggestions for diagnosis and follow-up visits and pharmacological therapies for treatment and prophylaxis. Further topics comprise special aspects in children and adults with severe haemophilia, outcome measurement, and management of trauma, special bleedings and interventions, including dental procedures, inhibitors, management of haemophilia carriers, and psychosocial aspects.