Differentiation of Monofloral Honey Using Volatile Organic Compounds by HS-GCxIMS.

Honey is a natural product and can be described by its botanical origin, determined by the plants from which the bees collect nectar. It significantly influences the taste of honey and is often used as a quality criterion. Unfortunately, this opens up the possibility of food fraud. Currently, various methods are used to check the authenticity of monofloral honey. The laborious, manual melissopalynology is considered an essential tool in the verification process. In this work, the volatile organic compounds obtained from the headspace of honey are used to prove their authenticity. The headspace of 58 honey samples was analyzed using a commercial easy-to-use gas chromatography-coupled ion mobility spectrometer with a headspace sampler (HS-GCxIMS). The honey samples were successfully differentiated by their six different botanical origins using specific markers with principal component analysis in combination with linear discriminant analysis. In addition, 15 honey-typical compounds were identified using measurements of reference compounds. Taking a previously published strategy, retention times of marker compounds were correlated with GC-coupled mass spectrometry (GC-MS) measurements to assist in the identification process.

Resolution-optimized headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) for non-targeted olive oil profiling.

A prototype gas chromatography-ion mobility spectrometry (GC-IMS) system, hyphenating temperature-ramped headspace GC to a modified drift time IMS cell, was evaluated and compared to a conventional, isothermal capillary column (CC)-IMS system on the example of the geographical differentiation of extra virgin olive oils (EVOO) from Spain and Italy. It allows orthogonal, 2D separation of complex samples and individual detection of compounds in robust and compact benchtop systems. The information from the high-resolution 3D fingerprints of volatile organic compound (VOC) fractions of EVOO samples were extracted by specifically developed chemometric MATLAB® routines to differentiate between the different olive oil provenances. A combination of unsupervised principal component analysis (PCA) with two supervised procedures, linear discriminant analysis (LDA) and k-nearest neighbors (kNN), was applied to the experimental data. The results showed very good discrimination between oils of different geographical origins, featuring 98 and 92% overall correct classification rate for PCA-LDA and kNN classifier, respectively. Furthermore, the results showed that the higher resolved 3D fingerprints obtained from the GC-IMS system provide superior resolving power for non-targeted profiling of VOC fractions from highly complex samples such as olive oil. Graphical abstract Principle of the determination of geographic origins of olive oils by chemometric analysis of three-dimensional HS-GC-IMS fingerprints.

Identification and characterization of Hoxa9 binding sites in hematopoietic cells.

The clustered homeobox proteins play crucial roles in development, hematopoiesis, and leukemia, yet the targets they regulate and their mechanisms of action are poorly understood. Here, we identified the binding sites for Hoxa9 and the Hox cofactor Meis1 on a genome-wide level and profiled their associated epigenetic modifications and transcriptional targets. Hoxa9 and the Hox cofactor Meis1 cobind at hundreds of highly evolutionarily conserved sites, most of which are distant from transcription start sites. These sites show high levels of histone H3K4 monomethylation and CBP/P300 binding characteristic of enhancers. Furthermore, a subset of these sites shows enhancer activity in transient transfection assays. Many Hoxa9 and Meis1 binding sites are also bound by PU.1 and other lineage-restricted transcription factors previously implicated in establishment of myeloid enhancers. Conditional Hoxa9 activation is associated with CBP/P300 recruitment, histone acetylation, and transcriptional activation of a network of proto-oncogenes, including Erg, Flt3, Lmo2, Myb, and Sox4. Collectively, this work suggests that Hoxa9 regulates transcription by interacting with enhancers of genes important for hematopoiesis and leukemia.

A simple and efficient synthesis of functionalized cyclic carbonate monomers using a versatile pentafluorophenyl ester intermediate.

An improved two-step synthetic route to functionalized cyclic carbonate monomers that features a novel cyclic carbonate intermediate with an active pentafluorophenyl ester group (MTC-OPhF(5)) has been developed. The versatile pentafluorophenyl ester intermediate can be synthesized on the gram to kilogram scale in one high-yielding step and is easy to store and handle on the benchtop. The active pentafluorophenyl ester of MTC-OPhF(5) is amenable to further substitution with suitable nucleophiles such as alcohols and amines to generate functionalized cyclic carbonates in high yields. The substitution reaction is tolerant of a wide variety of functionalities, including various hydrophobic and hydrophilic groups, reactive functionalities (via thiol-ene click chemistry or alkyl halides), and protected acids, alcohols, thiols, and amines. In view of the ever-increasing need for biodegradable and biocompatible polymers, this new methodology provides a simple and versatile platform for the synthesis of new and innovative materials.

Jigsaw: engaging communities in the development and implementation of youth mental health services and supports in the Republic of Ireland.

BACKGROUND: Irish young people exhibit high levels of psychological distress, but community-based services and supports are often unavailable or inaccessible. AIM: To describe efforts to engage communities in systematic and data-based processes of planning, programme design, implementation, and evaluation. METHOD: Details system-building initiatives in five communities (four counties and a distressed urban site) that will serve as a springboard for full national deployment. RESULTS: Extensive community engagement and planning has occurred in all sites, systems change efforts grounded in detailed business plans have begun, and process and outcome evaluation is underway. CONCLUSION: Needs and resource assessment processes confirmed the magnitude of need, but also suggested the creative re-allocation of local resources. Young people provided invaluable guidance for system design. Creating and sustaining a culture of innovation at each site was challenging, requiring leadership and continuous dialogue.

Treating systemic issues in families affected by cystic fibrosis: A solution-focused approach.

Cystic fibrosis (CF) presents with various symptoms that impair day-to-day functioning and require lifelong treatment. Due to the chronic and severe nature of this disease, families are often impacted by the stress associated with treatment, complications of the disease, and the understanding that their loved one will one day die from CF. This article seeks to address a perceived gap in the literature for providing a model-specific approach to address psychosocial stress in families affected by CF. We provide a rationale for using solution-focused brief therapy (SFBT) to work with this population based on its empirically supported effectiveness, versatility, and capacity to be brief in nature. We describe how SFBT interventions can be used by practitioners working with this population, present a fictitious case illustration depicting the clinical use of specific SFBT interventions, and offer suggestions for future research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Overview of HF10 spinal cord stimulation for the treatment of chronic pain and an introduction to the Senza Omnia™ system.

Chronic intractable pain affects a significant percentage of the worldwide population, and it is one of the most disabling and expensive health conditions across the globe. Spinal cord stimulation (SCS) has been used to treat chronic pain for a number of years, but high-frequency SCS was not the US FDA approved until 2015. In this review, we describe the history and development of high-frequency SCS and discuss the benefits of the Omnia™ implantable pulse generator. We also provide a thorough literature review of the published work, highlighting the efficacy and safety profiles of high-frequency SCS for the treatment of multiple chronic pain conditions. Lastly, we offer our outlook on future developments with the Omnia SCS system.

Diagnosis of COVID-19 by analysis of breath with gas chromatography-ion mobility spectrometry - a feasibility study.

BACKGROUND: There is an urgent need to rapidly distinguish COVID-19 from other respiratory conditions, including influenza, at first-presentation. Point-of-care tests not requiring laboratory- support will speed diagnosis and protect health-care staff. We studied the feasibility of using breath-analysis to distinguish these conditions with near-patient gas chromatography-ion mobility spectrometry (GC-IMS). METHODS: Independent observational prevalence studies at Edinburgh, UK, and Dortmund, Germany, recruited adult patients with possible COVID-19 at hospital presentation. Participants gave a single breath-sample for VOC analysis by GC-IMS. COVID-19 infection was identified by transcription polymerase chain reaction (RT- qPCR) of oral/nasal swabs together with clinical-review. Following correction for environmental contaminants, potential COVID-19 breath-biomarkers were identified by multi-variate analysis and comparison to GC-IMS databases. A COVID-19 breath-score based on the relative abundance of a panel of volatile organic compounds was proposed and tested against the cohort data. FINDINGS: Ninety-eight patients were recruited, of whom 21/33 (63.6%) and 10/65 (15.4%) had COVID-19 in Edinburgh and Dortmund, respectively. Other diagnoses included asthma, COPD, bacterial pneumonia, and cardiac conditions. Multivariate analysis identified aldehydes (ethanal, octanal), ketones (acetone, butanone), and methanol that discriminated COVID-19 from other conditions. An unidentified-feature with significant predictive power for severity/death was isolated in Edinburgh, while heptanal was identified in Dortmund. Differentiation of patients with definite diagnosis (25 and 65) of COVID-19 from non-COVID-19 was possible with 80% and 81.5% accuracy in Edinburgh and Dortmund respectively (sensitivity/specificity 82.4%/75%; area-under-the-receiver- operator-characteristic [AUROC] 0.87 95% CI 0.67 to 1) and Dortmund (sensitivity / specificity 90%/80%; AUROC 0.91 95% CI 0.87 to 1). INTERPRETATION: These two studies independently indicate that patients with COVID-19 can be rapidly distinguished from patients with other conditions at first healthcare contact. The identity of the marker compounds is consistent with COVID-19 derangement of breath-biochemistry by ketosis, gastrointestinal effects, and inflammatory processes. Development and validation of this approach may allow rapid diagnosis of COVID-19 in the coming endemic flu seasons. FUNDING: MR was supported by an NHS Research Scotland Career Researcher Clinician award. DMR was supported by the University of Edinburgh ref COV_29.

Spatial Control of the Self-assembled Block Copolymer Domain Orientation and Alignment on Photopatterned Surfaces.

Polarity-switching photopatternable guidelines can be directly used to both orient and direct the self-assembly of block copolymers. We report the orientation and alignment of poly(styrene-block-4-trimethylsilylstyrene) (PS-b-PTMSS) with a domain periodicity, L0, of 44 nm on thin photopatternable grafting surface treatments (pGSTs) and cross-linkable surface treatments (pXSTs), containing acid-labile 4-tert-butoxystyrene monomer units. The surface treatment was exposed using electron beam lithography to create well-defined linear arrays of neutral and preferential regions. Directed self-assembly (DSA) of PS-b-PTMSS with much lower defectivity was observed on pXST than on pGST guidelines. The study of the effect of film thickness on photoacid diffusion by Fourier transform infrared spectroscopy and near-edge X-ray absorption fine structure spectroscopy suggested slower diffusion in thinner films, potentially enabling production of guidelines with sharper interfaces between the unexposed and exposed lines, and thus, the DSA of PS-b-PTMSS on thinner pXST guidelines resulted in better alignment control.

Hydrogen-bonding catalysts based on fluorinated alcohol derivatives for living polymerization.

Recognize this! A hydrogen-bonding motif based on hexafluorinated alcohol derivatives (see picture; O red, F yellow) activates electrophilic substrates. The catalytic activity of the hydrogen-bonded systems was demonstrated for the ring-opening polymerization of a variety of strained heterocycles. Narrowly dispersed polymers with predictable molecular weights were obtained with end-group fidelity.

MDS with 5q deletion and rare cKIT positive mastocytosis: a diagnostic and therapeutic challenge.

A patient with a diagnosis of myelodysplastic syndrome (MDS) with isolated 5q deletion underwent repeat bone marrow biopsy to assess haematological response after 6 months of initial lenalidomide therapy. Subsequent bone marrow biopsies revealed persistent MDS with del(5q) in addition to a small atypical mast cell population with >25% of mast cells with spindle-shaped morphology and immunohistochemistry characteristics consistent with mastocytosis. Molecular testing on the bone marrow was positive for cKIT D816V and the patient was diagnosed with systemic mastocytosis (SM) with an associated haematological neoplasm. MDS with SM is well known to be associated; however, to the best of our knowledge, only one prior case report identifies MDS with del(5q) and associated cKIT D816V positive mastocytosis. While the exact clonal origin of both chromosomal aberrations is unclear, this case illustrates the therapeutic efficacy of lenalidomide in a patient with MDS with del(5q) and rarely associated cKIT positive SM.

Chronic Myeloid Leukemia with b3a3 (e14a3) Fusion: A Rare BCR/ABL Rearrangement Presenting with Thrombocytosis - Does MTHFR Polymorphism Matter.

Fusion of b2a2 is the most common BCR/ABL rearrangement in CML; however, absent a2 exons are very rare. We describe a case with Philadelphia-positive chronic myeloid leukemia (CML) with a very rare b3a3 (e14a3) BCR/ABL junction. To our knowledge, only 15 such cases of CML have previously been reported. These uncommon transcripts may be under-reported, since RT-PCR-based assays may fail to detect these fusions due to the location of the primers and probes used. We are reporting this case for the first time which presented with MTHFR mutation and significant thrombocytosis. There is very limited information on how this genotype expresses and responds to treatment, especially to tyrosine kinase inhibitors, as compared to classic CML. Also, the relationship between MTHFR mutation and CML is not clear, although studies have been done.

Chronic Poststernotomy Pain: Incidence, Risk Factors, Treatment, Prevention, and the Anesthesiologist's Role.

Chronic pain following median sternotomy is common after cardiac surgery. If left untreated, chronic sternal pain can reduce quality of life, affecting sleep, mood, activity level, and overall satisfaction. This has a significant societal effect given the large number of cardiac surgeries annually. Although a number of pathophysiologic processes and risk factors are assumed to contribute, the exact cause and major risk factors remain unknown. Moreover, the treatment of chronic poststernotomy pain is often inadequate, relying on opioids and other medications that provide minimal benefit to the patient and have significant adverse effects. Indeed, little is known regarding the prevention of chronic pain development following sternotomy. This review aims to present the current, limited data regarding the incidence, risk factors, treatment, and prevention of chronic poststernotomy pain and to identify areas of future research to improve management of this common complaint following cardiac surgery.

Surface Assembly Configurations and Packing Preferences of Fibrinogen Mediated by the Periodicity and Alignment Control of Block Copolymer Nanodomains.

The ability to control the specific adsorption and packing behaviors of biomedically important proteins by effectively guiding their preferred surface adsorption configuration and packing orientation on polymeric surfaces may have utility in many applications such as biomaterials, medical implants, and tissue engineering. Herein, we investigate the distinct adhesion configurations of fibrinogen (Fg) proteins and the different organization behaviors between single Fg molecules that are mediated by the changes in the periodicity and alignment of chemically alternating nanodomains in thin films of polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) block copolymer (BCP). Specifically, the adsorption characteristics of individual Fg molecules were unambiguously resolved on four different PS-b-PMMA templates of dsa PS-b-PMMA, sm PS-b-PMMA, com PS-b-PMMA, and PS-r-PMMA. By direct visualization through high resolution imaging, the distinct adsorption and packing configurations of both isolated and interacting Fg molecules were determined as a function of the BCP template-specific nanodomain periodicity, domain alignment (random versus fully aligned), and protein concentration. The three dominant Fg adsorption configurations, SP∥, SP⊥, and TP, were observed and their occurrence ratios were ascertained on each PS-b-PMMA template. During surface packing, the orientation of the protein backbone was largely governed by the periodicity and alignment of the underlying PS-b-PMMA nanodomains whose specific direction was explicitly resolved relative to the polymeric nanodomain axis. The use of PS-b-PMMA with a periodicity much smaller than (and comparable to) the length of Fg led to a Fg scaffold with the protein backbone aligned parallel (and perpendicular) to the nanodomain major axis. In addition, we have successfully created fully Fg-decorated BCP constructs analogous to two-dimensional Fg crystals in which aligned protein molecules are arranged either side-on or end-on, depending on the BCP template. Our results demonstrate that the geometry and orientation of the protein can be effectively guided during Fg self-assembly by controlling the physical dimensions and orientations of the underlying BCP templates. Finally, the biofunctionality of the BCP surface-bound Fg was assessed and the Fg/BCP construct was successfully used in the Ca-P nanoparticle nucleation/growth and microglia cell activation.

A Clinical Comparison of Intravenous and Epidural Local Anesthetic for Major Abdominal Surgery.

BACKGROUND: Epidural analgesia provides good pain control after many postoperative procedures, but it can lead to complications, has some contraindications, and occasionally fails. Intravenous lidocaine infusion has been suggested as an alternative. We assessed, in our clinical practice, the effects of perioperative intravenous lidocaine infusion compared with epidural analgesia for major abdominal surgery. METHODS: We conducted a retrospective review of patients who had received intravenous lidocaine (1 mg/kg per hour) perioperatively after a major abdominal surgery. We matched them with patients who had received epidural analgesia. We tested a joint hypothesis of noninferiority of lidocaine infusion to epidural analgesia in postoperative pain scores and opioid consumption. We assigned a noninferiority margin of 1 point (on an 11-point numerical rating scale) difference in pain and a ratio [mean (lidocaine) / mean (epidural)] of 1.2 in opioid consumption, respectively. RESULTS: Two hundred sixteen patients (108 in each group) were analyzed. Intravenous lidocaine was not inferior to epidural analgesia with respect to pain scores. Lidocaine infusion was inferior to epidural analgesia with respect to opioid consumption. Patients in the lidocaine group had fewer episodes of hypotension and less postoperative nausea and vomiting, pruritus, and urinary retention. Patients receiving lidocaine also had earlier urinary catheter removal and earlier first gastrointestinal function. Daily mental status assessment was similar between the 2 groups. CONCLUSIONS: Patients who received systemic lidocaine infusions with the addition of PRN (as needed) opioids administered for breakthrough pain did not have clinically significant differences in pain scores on postoperative day 2 and beyond. Intravenous lidocaine infusion in major abdominal surgery was inferior to epidural analgesia with respect to opioid consumption. However, lidocaine was associated with improvements in several important aspects of recovery.

Nanoscale chemical imaging by photoinduced force microscopy.

Correlating spatial chemical information with the morphology of closely packed nanostructures remains a challenge for the scientific community. For example, supramolecular self-assembly, which provides a powerful and low-cost way to create nanoscale patterns and engineered nanostructures, is not easily interrogated in real space via existing nondestructive techniques based on optics or electrons. A novel scanning probe technique called infrared photoinduced force microscopy (IR PiFM) directly measures the photoinduced polarizability of the sample in the near field by detecting the time-integrated force between the tip and the sample. By imaging at multiple IR wavelengths corresponding to absorption peaks of different chemical species, PiFM has demonstrated the ability to spatially map nm-scale patterns of the individual chemical components of two different types of self-assembled block copolymer films. With chemical-specific nanometer-scale imaging, PiFM provides a powerful new analytical method for deepening our understanding of nanomaterials.

Orientation Control of Block Copolymers Using Surface Active, Phase-Preferential Additives.

Orientation control of thin film nanostructures derived from block copolymers (BCPs) are of great interest for various emerging technologies like separation membranes, nanopatterning, and energy storage. While many BCP compositions have been developed for these applications, perpendicular orientation of these BCP domains is still very challenging to achieve. Herein we report on a new, integration-friendly approach in which small amounts of a phase-preferential, surface active polymer (SAP) was used as an additive to a polycarbonate-containing BCP formulation to obtain perpendicularly oriented domains with 19 nm natural periodicity upon thermal annealing. In this work, the vertically oriented BCP domains were used to demonstrate next generation patterning applications for advanced semiconductor nodes. Furthermore, these domains were used to demonstrate pattern transfer into a hardmask layer via commonly used etch techniques and graphoepitaxy-based directed self-assembly using existing lithographic integration schemes. We believe that this novel formulation-based approach can easily be extended to other applications beyond nanopatterning.

Corrosion of high-level radioactive waste iron-canisters in contact with bentonite.

Several countries favor the encapsulation of high-level radioactive waste (HLRW) in iron or steel canisters surrounded by highly compacted bentonite. In the present study the corrosion of iron in contact with different bentonites was investigated. The corrosion product was a 1:1 Fe layer silicate already described in literature (sometimes referred to as berthierine). Seven exposition test series (60 °C, 5 months) showed slightly less corrosion for the Na-bentonites compared to the Ca-bentonites. Two independent exposition tests with iron pellets and 38 different bentonites clearly proved the role of the layer charge density of the swelling clay minerals (smectites). Bentonites with high charged smectites are less corrosive than bentonites dominated by low charged ones. The type of counterion is additionally important because it determines the density of the gel and hence the solid/liquid ratio at the contact to the canister. The present study proves that the integrity of the multibarrier-system is seriously affected by the choice of the bentonite buffer encasing the metal canisters in most of the concepts. In some tests the formation of a patina was observed consisting of Fe-silicate. Up to now it is not clear why and how the patina formed. It, however, may be relevant as a corrosion inhibitor.

Directed self-assembly of silicon-containing block copolymer thin films.

The directed self-assembly (DSA) of lamella-forming poly(styrene-block-trimethylsilylstyrene) (PS-PTMSS, L0=22 nm) was achieved using a combination of tailored top interfaces and lithographically defined patterned substrates. Chemo- and grapho-epitaxy, using hydrogen silsesquioxane (HSQ) based prepatterns, achieved density multiplications up to 6× and trench space subdivisions up to 7×, respectively. These results establish the compatibility of DSA techniques with a high etch contrast, Si-containing BCP that requires a top coat neutral layer to enable orientation.