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In the aftermath of the COVID-19 pandemic, opportunities to modulate biological pathways common to the lifecycles of viruses need to be carefully considered. N -linked glycosylation in humans is mediated exclusively by the oligosaccharyltransferase complex and is frequently hijacked by viruses to facilitate infection. As such, STT3A/B, the catalytic domain of the OST complex, became an intriguing drug target with broad-spectrum antiviral potential. However, due to the critical role N -linked glycosylation plays in a number of fundamental human processes, the toxicological ramifications of STT3A/B inhibition required attention commensurate to that given to antiviral efficacy. Herein, we describe how known STT3A/B inhibitor NGI-1 inspired the discovery of superior tool compounds which were evaluated in in vitro efficacy and translational safety (e.g., CNS, cardiovascular, liver) studies. The described learnings will appeal to those interested in the therapeutic utility of modulating N -linked glycosylation as well as the broader scientific community.

The purpose of this systematic review is to describe the pathoanatomy, presentation, diagnostic workup, treatment modalities, and outcomes of posterior interosseous nerve (PIN) palsy in patients with rheumatoid arthritis (RA). All reported cases of PIN palsy in patients with RA were reviewed to yield 72 cases of PIN palsy in 70 patients. The male-to-female ratio was 1:2.7. Pain involving the elbow was very common (20/33 cases reporting this information), and paralysis or weakness of digit extension was noted in 27/33 cases and 6/33 cases, respectively. Only 1 of the 54 cases undergoing surgical intervention reported persistent weakness, and this 1 patient had undergone a 3-month trial of conservative management. In conclusion, Appropriate pharmacologic management in conjunction with magnetic resonance imaging (MRI) and ultrasound monitoring may be used for conservative management, but surgical decompression should still be utilized for patients with a compressive disease pathology who fail to improve with 6 weeks of conservative treatment, or for those with advanced disease on initial presentation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Posttraumatic stress disorder (PTSD) after a stay in the intensive care unit (ICU) can affect one in five ICU survivors. At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, admission to the ICU for COVID-19 was stressful due to the severity of this disease. This study assessed whether admission to the ICU for COVID-19 was associated with a higher prevalence of PTSD compared with other causes of ICU admission after adjustment for pre-ICU psychological factors., Methods: This prospective observational comparative cohort study included 31 ICUs. Eligible patients were adult ICU survivors hospitalized during the first wave of COVID-19 pandemic in France, regardless of the reason for admission. The prevalence of presumptive diagnosis of PTSD at 6 months was assessed using the PTSD Checklist for DSM-5 (PCL-5). Sociodemographics, clinical data, history of childhood trauma (Childhood Trauma Questionnaire [CTQ]), and exposure to potentially traumatic events (Life Events Checklist for DSM-5 [LEC-5]) were assessed., Results: Of the 778 ICU survivors included during the first wave of COVID-19 pandemic in France, 417 and 361 were assigned to the COVID-19 and non-COVID-19 cohorts, respectively. Fourteen (4.9%) and 11 (4.9%), respectively, presented with presumptive diagnosis of PTSD at 6 months (p = 0.976). After adjusting for age, sex, severity score at admission, use of invasive mechanical ventilation, ICU duration, CTQ and LEC-5, COVID-19 status was not associated with presumptive diagnosis of PTSD using the PCL-5. Only female sex was associated with presumptive diagnosis of PTSD. However, COVID-19 patients reported significantly more intrusion and avoidance symptoms than non-COVID patients (39% vs. 29%, p = 0.015 and 27% vs. 19%, p = 0.030), respectively. The median PCL-5 score was higher in the COVID-19 than non-COVID-19 cohort (9 [3, 20] vs. 4 [2, 16], p = 0.034)., Conclusion: Admission to the ICU for COVID-19 was not associated with a higher prevalence of PTSD compared with admission for another cause during the first wave of the COVID-19 pandemic in France. However, intrusion and avoidance symptoms were more frequent in COVID-19 patients than in non-COVID-19 patients., Trial Registration: Clinicaltrials.gov Identifier NCT03991611, registered on June 19, 2019., (© 2024. The Author(s).)

Nurturing the development of the next generation of resuscitation scientists is essential for creating a vibrant and enabled community equipped with the necessary knowledge, attitudes, and skills to transform resuscitation practice and improve outcomes. In this concept paper we will describe the development and implementation of the first Young European Resuscitation Council Resuscitation Science Masterclass. The masterclass aims to connect, inspire, and support the growth of the next generation of resuscitation scientists through education, networking, and joint scientific work. The masterclass provides 20 international, multi-professional early career resuscitation scientists with the opportunity to expand their knowledge and network as well as conduct joint scientific work over the course of one year. This is achieved by interactive webinars, innovative online workshops, engaging online journal clubs as well as an educational in-person event to conclude the masterclass. The Young European Resuscitation Council Resuscitation Science Masterclass aims to strengthen the global resuscitation community and next generation of resuscitation scientists by facilitating opportunities of broader international initiatives and collaboration for early career resuscitation scientists, potentially leading to accelerated recruitment of future resuscitation leaders. Ultimately, this masterclass may enable early career researchers to produce high impact research that can shape the future of resuscitation science and improve cardiac arrest patient care globally., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JW serves as the Interim Chair of the Young ERC; BK serves as the Young ERC Young Investigator Representative; RG serves as the ERC Director of Guidelines and ILCOR, and is the Task Force Chair Education, Implementation and Team of ILCOR. He is an editorial board member of Resuscitation Plus. GDP serves as the ERC Director of Science and Research and is the Editor-in-Chief of Resuscitation Plus; KGL serves as the Young ERC Neonatal Life Support Representative, Young ERC Resuscitation Plus Editor, and ERC Advanced Life Support Science and Education Committee member., (© 2023 The Author(s).)

Molecular dynamic modeling and various experimental techniques, including multi-angle dynamic light scattering (MADLS), streaming potential, optical waveguide light spectroscopy (OWLS), quartz crystal microbalance with dissipation (QCM), and atomic force microscopy (AFM), were applied to determine the basic physicochemical parameters of fibroblast growth factor 21 in electrolyte solutions. The protein size and shape, cross-section area, dependence of the nominal charge on pH, and isoelectric point of 5.3 were acquired. These data enabled the interpretation of the adsorption kinetics of FGF 21 on bare and macrocation-covered silica investigated by OWLS and QCM. It was confirmed that the protein molecules irreversibly adsorbed on the latter substrate, forming layers with controlled coverage up to 0.8 mg m -2 , while their adsorption on bare silica was much smaller. The viability of two cell lines, CHO-K1 and L-929, on both bare and macrocation/FGF 21-covered substrates was also determined. It is postulated that the acquired results can serve as useful reference systems for designing complexes that can extend the half-life of FGF 21 in its active state.

Biomaterial science has contributed tremendously to developing nanoscale materials for delivering biologically active compounds, enhancing protein stability, and enabling its therapeutic use. This paper presents a process of formation of polyelectrolyte multilayer (PEM) prepared by sequential adsorption of positively charged polydiallyldimethylammonium chloride (PDADMAC) and negatively charged heparin sodium salt (HP), from low polyelectrolyte concentration, on a solid substrate. PEM was further applied as a platform for the adsorption of a brain-derived growth factor (BDNF), which is a protein capable of regulating neuronal cell development. The multilayers containing BDNF were thoroughly characterized by electrokinetic (streaming potential measurements, SPM) and optical (optical waveguide lightmode spectroscopy, OWLS) techniques. It was found that BDNF was significantly adsorbed onto polyelectrolyte multilayers terminated by HP under physiological conditions. We further explore the effect of established PEMs in vitro on the neuroblastoma SH-SY5Y cell line. An enzyme-linked immunosorbent assay (ELISA) confirmed that BDNF was released from multilayers, and the use of the PEMs intensified its cellular uptake. Compared to the control, PEMs with adsorbed BDNF significantly reduced cell viability and mitochondrial membrane polarization to as low as 72% and 58%, respectively. HPLC analysis showed that both PDADMAC-terminated and HP-terminated multilayers have antioxidative properties as they almost by half decreased lipid peroxidation in SH-SY5Y cells. Finally, enhanced formation of spheroid-like, 3D structures was observed by light microscopy. We offer a well-characterized PEM with antioxidant properties acting as a BDNF carrier, stabilizing BDNF and making it more accessible to cells in an inhomogeneous, dynamic, and transient in vitro environment. Described multilayers can be utilized in future biomedical applications, such as boosting the effect of treatment by selective anticancer as adjuvant therapy, and in biomedical research for future development of more precise neurodegenerative disease models, as they enhance cellular 3D structure formation., (© 2023. Springer Nature Limited.)

Introduction: We have previously described negative energy balance (ie, -9.7±3.4 MJ/d) and weight loss (Δ-1.5 ± 0.7 kg) influenced by high levels of energy expenditure (ie, 17.4±2.6 MJ/d) during remote expeditionary hunting in Alaska. Despite negative energy balance, participants retained skeletal muscle. The purpose of this pilot study was to measure skeletal muscle protein synthesis and examine molecular markers of skeletal muscle protein metabolism under similar conditions of physical and nutrient stress., Methods: The "virtual biopsy method" was used to evaluate integrated fractional synthetic rates (FSRs) of muscle protein from blood samples in 4 participants. Muscle biopsies were taken to measure molecular markers of muscle protein kinetics (ie, FSTL1, MEF2, MYOD1, B2M, and miR-1-3p, -206, -208b, 23a, and 499a) using real-time polymerase chain reaction., Results: Our findings in 4 participants (2 females [28 and 62 y of age; 66.2 and 71.8 kg body weight; 25.5 and 26.7 kg/m 2 body mass index] and 2 males [47 and 56 y of age; 87.5 and 91.4 kg body weight; 26.1 and 28.3 kg/m 2 body mass index]) describe mean muscle FSRs of serum carbonic anhydrase (2.4%) and creatine kinase M-type (4.0%) and positive increments in molecular regulation., Conclusions: Preservation of skeletal muscle under conditions of physical and nutrient stress seems to be supported by positive inflection of skeletal muscle FSR and molecular activation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Since the outbreak of the COVID-19 pandemic, the authorities of Serbia have undertaken a concerted effort to secure China's support in containing the coronavirus. This asymmetrical cooperation, apart from aspects concerning health security, has allowed both sides to obtain considerable political and economic benefits. This article examines how China and Serbia utilize pandemic cooperation to pursue and realize their wider foreign and internal policy goals through patron-client ties, as well as highlighting the pitfalls of this kind of relationship. Although the outbreak of the pandemic and the medical cooperation that followed do not constitute a turning point in the well-established relations between the two countries, the article argues that pandemic cooperation has considerably strengthened relations. In many ways, the pattern observed by the authors resembles China's pandemic exchanges with other countries, especially smaller states with authoritarian inclinations., (© The Author(s) 2023.)

Aspergillus fumigatus is a devastating opportunistic fungal pathogen causing hundreds of thousands of deaths every year. Phosphoglucose isomerase (PGI) is a glycolytic enzyme that converts glucose-6-phosphate to fructose-6-phosphate, a key precursor of fungal cell wall biosynthesis. Here, we demonstrate that the growth of A. fumigatus is repressed by the deletion of pgi , which can be rescued by glucose and fructose supplementation in a 1:10 ratio. Even under these optimized growth conditions, the Δ pgi mutant exhibits severe cell wall defects, retarded development, and attenuated virulence in Caenorhabditis elegans and Galleria mellonella infection models. To facilitate exploitation of A. fumigatus PGI as an antifungal target, we determined its crystal structure, revealing potential avenues for developing inhibitors, which could potentially be used as adjunctive therapy in combination with other systemic antifungals. IMPORTANCE Aspergillus fumigatus is an opportunistic fungal pathogen causing deadly infections in immunocompromised patients. Enzymes essential for fungal survival and cell wall biosynthesis are considered potential drug targets against A. fumigatus. PGI catalyzes the second step of the glycolysis pathway, linking glycolysis and the pentose phosphate pathway. As such, PGI has been widely considered as a target for metabolic regulation and therefore a therapeutic target against hypoxia-related diseases. Our study here reveals that PGI is important for A. fumigatus survival and exhibit pleiotropic functions, including development, cell wall glucan biosynthesis, and virulence. We also solved the crystal structure of PGI, thus providing the genetic and structural groundwork for the exploitation of PGI as a potential antifungal target.

Due to the antisurfactant properties of arsenic atoms, the self-induced dodecagonal GaN microrods can be grown by molecular beam epitaxy (MBE) in Ga-rich conditions. Since temperature is a key parameter in MBE growth, the role of temperature in the growth of GaN microrods is investigated. The optimal growth temperature window for the formation of GaN microrods is observed to be between 760 and 800 °C. Lowering the temperature to 720 °C did not change the growth mechanism, but the population of irregular and amorphous microrods increased. On the other hand, increasing the growth temperature up to 880 °C interrupts the growth of GaN microrods, due to the re-evaporation of the gallium from the surface. The incorporation of As in GaN microrods is negligible, which is confirmed by X-ray diffraction and transmission electron microscopy. Moreover, the photoluminescence and cathodoluminescence characteristics typical for GaN are observed for individual GaN microrods, which additionally confirms that arsenic is not incorporated inside microrods. When the growth temperature is increased, the emission related to the band gap decreases in favor of the defect-related emission. This is typical for bulk GaN and attributed to an increase in the point defect concentration for GaN microrods grown at lower temperatures., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Purpose: Immune-checkpoint inhibitors (ICI) present a new treatment for malignancies by boosting the immune system. This has led to a variety of immune-related adverse events, including ICI-associated pneumonitis (ICIaP). Diagnosis thereof is often challenging, and its pathogenesis has not yet been fully understood. The aim of this cross-sectional case-control study was to investigate cytokines in serum and bronchoalveolar lavage fluid (BALF) expressed in patients with ICIaP compared to controls consisting of healthy individuals, patients with lung cancer and patients with interstitial lung diseases (ILD) other than ICIaP., Methods: From January 2018 until June 2019, 401 adult patients with various lung diseases were prospectively enrolled in a BALF- and serum biobank, called BALOTHEK. Of these, 12 patients were diagnosed with ICIaP (Pembrolizumab, Ipilimumab, or both, and Durvalumab) serving as case group. Subjects with one of three diagnosis groups from BALOTHEK, including lung cancer, ILD other than ICIaP, and healthy individuals, served as matched controls. The following 11 cytokines were simultaneously analyzed in BALF and serum of each study participant: interferon gamma, tumor necrosis factor alpha, interleukin (IL) 1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-12p70, IL-13 and IL-17A. This study was approved by the local ethic review committee (BASEC-ID 2017-02,307 and 2018-01,724)., Results: Absolute number and percentage of lymphocytes in BALF of patients with ICIaP were significantly higher compared to control groups. For the investigated cytokines in BALF, a significant increase of IL-6 level was shown for patients with ICIaP compared to control groups (p = 0.031, adjusted for multiple comparisons)., Conclusion: Cytokine profile assessed in BALF shows promising potential for facilitating diagnosis and understanding of pathophysiology of ICIaP. IL-6 may not only contribute to better understanding of pathophysiology but also herald therapeutic implications for Tocilizumab., (© 2021. The Author(s).)

Aspergillus fumigatus is the causative agent of invasive aspergillosis, an infection with mortality rates of up to 50%. The glucan-rich cell wall of A. fumigatus is a protective structure that is absent from human cells and is a potential target for antifungal treatments. Glucan is synthesized from the donor uridine diphosphate glucose, with the conversion of glucose-6-phosphate to glucose-1-phosphate by the enzyme phosphoglucomutase (PGM) representing a key step in its biosynthesis. Here, we explore the possibility of selectively targeting A. fumigatus PGM (AfPGM) as an antifungal treatment strategy. Using a promoter replacement strategy, we constructed a conditional pgm mutant and revealed that pgm is required for A. fumigatus growth and cell wall integrity. In addition, using a fragment screen, we identified the thiol-reactive compound isothiazolone fragment of PGM as targeting a cysteine residue not conserved in the human ortholog. Furthermore, through scaffold exploration, we synthesized a para-aryl derivative (ISFP10) and demonstrated that it inhibits AfPGM with an IC 50 of 2 μM and exhibits 50-fold selectivity over the human enzyme. Taken together, our data provide genetic validation of PGM as a therapeutic target and suggest new avenues for inhibiting AfPGM using covalent inhibitors that could serve as tools for chemical validation., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

In this paper, we report on a successful synthesis of dysprosium iron garnet Dy 3 Fe 5 O 12 (DyIG) by a reactive synthesis method involving dysprosium iron perovskite and hematite. Phase formation was traced using dilatometry, and XRD measurements attested to the formation of the desired structure. Samples with relative density close to 97% were fabricated. The samples were characterized using vibrating sample magnetometry, dielectric spectroscopy, and UV-Vis-NIR spectroscopy. Magnetic properties were probed in temperatures between 80 and 700 K with a maximum applied field of 1 kOe. The measurements revealed several effects: the compensation of magnetic moments at a certain temperature, the inversion of the magnetocaloric effect, and the ability to measure the Curie temperature of the material. Activation energy was determined from UV-Vis-NIR and dielectric spectroscopy measurements. Characteristic magnetic temperatures and activation energy values of the samples were similar to bulk DyIG obtained using other methods.

Titanium alloys are used in skeletal surgery. However, once bone union is complete, such fixation material becomes unnecessary or even harmful. Resorbable magnesium materials have been available for several years (WE43 alloy). The aim of this study was to clinically compare magnesium versus titanium open reduction and rigid fixations in mandible condylar heads. Ten patients were treated for fractures of the mandibular head with magnesium headless compression screws (2.3 mm in diameter), and 11 patients were included as a reference group with titanium screws (1.8 mm in diameter) with similar construction. The fixation characteristics (delay, time, and number of screws), distant anatomical results (mandibular ramus height loss, monthly loss rate, and relative loss of reconstructed ramus height), basic functional data (mandibular movements, facial nerve function, and cutaneous perception) and the influence of the effects of the injury (fracture type, fragmentation, occlusion, additional fractures, and associated diseases) on the outcome were evaluated. The long-term results of treatment were evaluated after 18 months. Treatment results similar to those of traditional titanium fixation were found with magnesium screws. Conclusions: Resorbable metal screws can be a favored option for osteosynthesis because surgical reentry can be avoided. These materials provide proper and stable treatment results.

This paper presents the results of the experimental research of 3D structures developed with an SLA additive technique using Durable Resin V2. The aim of this paper is to evaluate and compare the compression curves, deformation process and energy-absorption parameters of the topologies with different characteristics. The structures were subjected to a quasi-static axial compression test. Five different topologies of lattice structures were studied and compared. In the initial stage of the research, the geometric accuracy of the printed structures was analysed through measurement of the diameter of the beam elements at several selected locations. Compression curves and the stress history at the minimum cross-section of each topology were determined. Energy absorption parameters, including absorbed energy (AE) and specific absorbed energy (SAE), were calculated from the compression curves. Based on the analysis of the photographic material, the failure mode was analysed, and the efficiency of the topologies was compared.

Optical scanners are widely used in high-resolution scientific, medical, and industrial devices. The accuracy and precision of these instruments are often limited by angular speed fluctuations due to rotational inertia and by poor synchronization between scanning and light detection, respectively. Here we demonstrate that both problems can be mitigated by recording scanner orientation in synchrony with light detection, followed by data resampling. This approach is illustrated with synthetic and experimental data from a point-scanning microscope with a resonant scanner and a non-resonant scanner. Fitting of the resonant scanner orientation data to a cosine model was used to correct image warping and sampling jitter, as well as to precisely interleave image lines collected during the clockwise and counterclockwise resonant scanner portions of the rotation cycle. Vertical scanner orientation data interpolation was used to correct image distortion due to angular speed fluctuations following abrupt control signal changes.

Dynamic mirror deformation can substantially degrade the performance of optical instruments using resonant scanners. Here, we evaluate two scanners with resonant frequencies >12 k H z with low dynamic distortion. First, we tested an existing galvanometric motor with a novel, to the best of our knowledge, mirror substrate material, silicon carbide, which resonates at 13.8 kHz. This material is stiffer than conventional optical glasses and has lower manufacturing toxicity than beryllium, the stiffest material currently used for this application. Then, we tested a biaxial microelectromechanical (MEMS) scanner with the resonant axis operating at 29.4 kHz. Dynamic deformation measurements show that wavefront aberrations in the galvanometric scanner are dominated by linear oblique astigmatism (90%), while wavefront aberrations in the MEMS scanner are dominated by horizontal coma (30%) and oblique trefoil (27%). In both scanners, distortion amplitude increases linearly with deflection angle, yielding diffraction-limited performance over half of the maximum possible deflection for wavelengths longer than 450 nm and over the full deflection range for wavelengths above 850 nm. Diffraction-limited performance for shorter wavelengths or over larger fractions of the deflection range can be achieved by reducing the beam diameter at the mirror surface. The small dynamic distortion of the MEMS scanner offers a promising alternative to galvanometric resonant scanners with desirable but currently unattainably high resonant frequencies.

Mesothelin (MSLN), a glycoprotein normally expressed by mesothelial cells, is overexpressed in ovarian cancer (OvCa) suggesting a role in tumor progression, although the biological function is not fully understood. OvCa has a high mortality rate due to diagnosis at advanced stage disease with intraperitoneal metastasis. Tumor cells detach from the primary tumor as single cells or multicellular aggregates (MCAs) and attach to the mesothelium of organs within the peritoneal cavity producing widely disseminated secondary lesions. To investigate the role of host MSLN in the peritoneal cavity we used a mouse model with a null mutation in the MSLN gene (MSLN KO ). The deletion of host MSLN expression modified the peritoneal ultrastructure resulting in abnormal mesothelial cell surface architecture and altered omental collagen fibril organization. Co-culture of murine OvCa cells with primary mesothelial cells regardless of MSLN expression formed compact MCAs. However, co-culture with MSLN KO mesothelial cells resulted in smaller MCAs. An allograft tumor study, using wild-type mice (MSLN WT ) or MSLN KO mice injected intraperitoneally with murine OvCa cells demonstrated a significant decrease in peritoneal metastatic tumor burden in MSLN KO mice compared to MSLN WT mice. Together, these data support a role for host MSLN in the progression of OvCa metastasis.

An off-axis monocular pupil tracker designed for eventual integration in ophthalmoscopes for eye movement stabilization is described and demonstrated. The instrument consists of light-emitting diodes, a camera, a field-programmable gate array (FPGA) and a central processing unit (CPU). The raw camera image undergoes background subtraction, field-flattening, 1-dimensional low-pass filtering, thresholding and robust pupil edge detection on an FPGA pixel stream, followed by least-squares fitting of the pupil edge pixel coordinates to an ellipse in the CPU. Experimental data suggest that the proposed algorithms require raw images with a minimum of ∼32 gray levels to achieve sub-pixel pupil center accuracy. Tests with two different cameras operating at 575, 1250 and 5400 frames per second trained on a model pupil achieved 0.5-1.5 μm pupil center estimation precision with 0.6-2.1 ms combined image download, FPGA and CPU processing latency. Pupil tracking data from a fixating human subject show that the tracker operation only requires the adjustment of a single parameter, namely an image intensity threshold. The latency of the proposed pupil tracker is limited by camera download time (latency) and sensitivity (precision)., Competing Interests: The authors declare no conflicts of interest., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Introduction: Lung cancer is the leading cause of death by cancer. In recent years, immunotherapy with checkpoint inhibitors (ICI) emerged as a promising new therapeutic approach. However, a deeper understanding of the immunologic responses adjacent to the tumor known as tumor microenvironment (TME) is needed. Our study investigated TME of lung cancer by analyzing cytokines in bronchoalveolar lavage fluid (BALF)., Materials and Methods: Between January 2018 and June 2019, 119 patients were prospectively enrolled in this study. For each cancer patient, levels of 16 cytokines (fractalkine, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukins (IL): IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, and IL-23) were measured in BALF and serum and compared to healthy individuals and patients with other lung diseases., Results: There were several significant differences of cytokine levels of patients with lung cancer compared to healthy individuals. However, none of them remained in the multivariate analysis compared to other lung diseases in either BALF or serum. Furthermore, there were no significant differences between the groups in cell differentiation of either BALF or serum. Cytokine levels in BALF were generally near the lower detection limit and showed almost no correlation with their respective levels measured in serum of the same individual., Conclusions: Cytokines in BALF and serum of lung cancer patients may indicate unspecific inflammation. BAL is not recommendable as a tool to investigate TME of lung cancer. Therefore, cytokines measured in BALF are probably not appropriate as predictors in patients treated with ICIs.

Modern treatment in the field of head and neck surgery aims for the least invasive therapy and places great emphasis on restorative treatment, especially in the case of injury and deformation corrective surgery. More and more often, surgeons use CAD/CAM (Computer-Aided Design and Computer-Aided Manufacturing) tools in their daily practice in the form of models, templates, and computer simulations of planning. These tools are based on DICOM (Digital Imaging and Communications in Medicine) files derived from computed tomography. They can be obtained from both fan-beam (FBCT) and cone-beam tomography (CBCT) acquisitions, which are subsequently segmented in order to transform them into a 1-bit 3D model, which is the basis for further CAD processes., Aim: Evaluation of differences in the dimensions of mandible condyle models in fan- versus cone-beam computer tomography for surgical treatment purposes., Methods: 499 healthy condyles were examined in CT-based 3D models of Caucasians aged 8-88 years old. Datasets were obtained from 66 CBCT and 184 FBCT axial image series (in each case, imaging both mandible condyles resulted in the acquisition of 132 condyles from CBCT and 368 condyles from FBCT) and were transformed into three-dimensional models by digital segmentation. Eleven different measurements were performed to obtain information whether there were any differences between FBCT and CBCT models of the same anatomical region., Results: 7 of 11 dimensions were significantly higher in FBCT versus lower in CBCT ( p < 0.05).

Mandible condyle fracture has been reported to constitute 9-45 % (Asprino and Consani, 2006), 14.1 % (Bataineh, 1998), 25-50 % (Silvennoinen, Iizuka, 1992), 32 % (Chrcanovic et al., 2004), and 38 % (Brasileiro and Passeri, 2006) of all mandible fractures (Kozakiewicz and Swiniarski, 2013). Small bone segments, limited available space for application of the fixation material and limited visibility of the operative field are common difficulties. To guarantee satisfactory treatment effects, anatomical reduction and proper fracture stability are necessary. The use of 3-4 screws in the upper section (proximal segment) provides adequate immobilization, which can be easily achieved when the condyle is low and wide. However, if the condyle is slender, it is not technically possible to fix 2 plates and 4 screws for osteosynthesis. Selection of the appropriate fixative material that will provide adequate rigidity during the healing period while simultaneously allowing proper construction of the lateral silhouette of the processus condylaris mandibulae to fix the plate remains a key consideration. The aim of this study was to evaluate clinico-anatomical classification of the condyle of mandible posture for traumatological purposes. Five hundred computer tomography virtual models were created, from which 11 measurements were made, and 2 indexes were calculated. Assessment of types based on the ratio of the condyle height index revealed a dichotomous division into high and short condyles. Statistically associated with the division, the Width&#95;neck&#95;basal (the width of the bone at the level of semilunar notch measured by a frontal projection perpendicular to line "A", as described by Neff (Neff et al., 2014)) measurement allowed the creation of the following clinico-anatomical classification: -slender-type condyles have a Width&#95;neck&#95;basal in the range of 4-8.5mm; -squad-type condyles have a Width&#95;neck&#95;basal in the range of 11.5-19.5mm. Patients with a Width&#95;neck&#95;basal value in the 8.5-11.5mm range cannot be classified using this method, and a different method to assess the lateral condylar silhouette must be used. The proposed clinic-anatomical classification method avoids the problems associated with incorrect osteosynthesis plate selection. Assignment to a group can be obtained by making one measurement (the Width&#95;neck&#95;basal). In that way, the optimal fixing material can be selected by the surgeon before the operation commences, with great intraoperation time savings., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Quadrant reflectance confocal and non-confocal scanning light ophthalmoscope images of the photoreceptor mosaic were recorded in a subject with congenital achromatopsia (ACHM) and a normal control. These images, captured with various circular and annular apertures, were used to calculate split-detection images, revealing two cone photoreceptor contrast mechanisms. The first contrast mechanism, maximal in the non-confocal 5.5-10 Airy disk diameter annular region, is unrelated to the cone reflectivity in confocal or flood illumination imaging. The second mechanism, maximal for confocal split-detection, is related to the cone reflectivity in confocal or flood illumination imaging that originates from the ellipsoid zone and/or inner-outer segment junction. Seeking to maximize image contrast, split-detection images were generated using various quadrant detector combinations, with opposite (diagonal) quadrant detectors producing the highest contrast. Split-detection generated with the addition of adjacent quadrant detector pairs, shows lower contrast, while azimuthal split-detection images, calculated from adjacent quadrant detectors, showed the lowest contrast. Finally, the integration of image pairs with orthogonal split directions was used to produce images in which the photoreceptor contrast does not change with direction., Competing Interests: A. Dubra is a consultant for Meira Gtx. J. Carroll received research support from AGTC and Meira Gtx, is a consultant for Meira Gtx, and has a personal financial interest in Translational Imaging Innovations., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

High-speed optical systems are revolutionizing biomedical imaging in microscopy, DNA sequencing, and flow cytometry, as well as numerous other applications, including data storage, display technologies, printing, and autonomous vehicles. These systems often achieve the necessary imaging or sensing speed through the use of resonant galvanometric optical scanners. Here, we show that the optical performance of these devices suffers due to the dynamic mirror distortion that arises from the variation in torque with angular displacement. In one of two scanners tested, these distortions result in a variation of signal-to-noise (Strehl) ratio by an order of magnitude across the field of view, degrading transverse resolution by more than a factor of 2. This mirror distortion could be mitigated through the use of stiffer materials, such as beryllium or silicon carbide, at the expense of surface roughness, as these cannot be polished to the same degree of smoothness as common optical glasses. The repeatability of the dynamic distortion indicates that computational and optical corrective methods are also possible., Competing Interests: Disclosures. The authors declare no conflicts of interest.

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-1780). The authors have no conflicts of interest to declare.

We demonstrate the generation of spectrally tunable phase-dependent wavefronts, using the 2D Airy as the primary test case, via a polymer-stabilized cholesteric liquid crystal (PSCLC) element. Specifically, we use a novel spatial light modulator (SLM) based projection system to photo-align the initial helix angle landscape of the PSCLC so that it imparts the appropriate cubic phase profile to the reflected beam. This element is spectrally selective, with a reflection bandwidth of ≈ 100 nm, and electrically tunable from λ = 530 nm to 760 nm. Under both green and red laser illumination, the element is shown to conditionally form an Airy beam depending on the position of the electrically tailored reflection band. We briefly demonstrate the generality of this approach by producing PSCLC elements which form a computer-generated hologram and a higher-order Mathieu beam.

Plant material is a rich source of valuable compounds such as flavanones. Their different forms influence bioavailability and biological activity, causing problems with the selection of plant material for specific purposes. The purpose of this research was to determine selected flavanone (eriodictyol, naringenin, liquiritigenin, and hesperetin) enantiomer contents in free form and bonded to glycosides by an RP-UHPLC-ESI-MS/MS method. Different parts (stems, leaves, and flowers) of goldenrod (Solidago virgaurea L.), lucerne (Medicago sativa L.), and phacelia (Phacelia tanacetifolia Benth.) were used. The highest content of eriodictyol was found in goldenrod flowers (13.1 μg/g), where it occurred mainly as the (S)-enantiomer, and the greatest proportion of the total amount was bonded to glycosides. The richest source of naringenin was found to be lucerne leaves (4.7 μg/g), where it was mainly bonded to glycosides and with the (S)-enantiomer as the dominant form. Liquiritigenin was determined only in lucerne, where the flowers contained the highest amount (1.2 μg/g), with the (R)-enantiomer as dominant aglycone form and the (S)-enantiomer as the dominant glycosylated form. The highest hesperetin content was determined in phacelia leaves (0.38 μg/g), where it was present in the form of a glycoside and only as the (S)-enantiomer. A comparison of the different analyte forms occurring in different plant parts was performed for the first time., (© 2019 Wiley Periodicals, Inc.)

Objective: Conventional complete denture protocols require several patient appointments with multiple laboratory procedures. There are multiple workflows incorporating digital technology that can expedite the process, whereas increasing predictability. The proposed digitally replicated denture technique (DRDT) demonstrates a predictable workflow for fabricating complete dentures for patients with existing dentures., Clinical Procedure: A patient's existing maxillary and mandibular complete dentures were scanned with an intraoral scanner. The generated STL was then printed using a desktop 3D printer. This served as a custom tray and record base to decrease patient chair time and associated laboratory procedures., Conclusion: The DRDT workflow incorporates digital technology into a complete denture protocol to minimize laboratory steps and chair time when fabricating complete dentures for patients with existing prostheses., Clinical Significance: The use of a digitally replicated denture using rapid prototyping can streamline the process of complete denture fabrication for patients with existing dentures., (© 2018 Wiley Periodicals, Inc.)

Background: Achilles tendon rupture is a common injury and the best treatment option remains uncertain between surgical and nonoperative methods. Biologic approaches using multipotent stem cells such as perivascular stem cells pose a possible treatment option, although there is currently a paucity of evidence regarding their clinical therapeutic use., Questions/purposes: The purpose of this study was to determine whether injected perivascular stem cells (PSCs) would (1) improve histologic signs of tendon healing (such as percent area of collagen); and (2) improve biomechanical properties (peak load or stiffness) in a rat model of Achilles tendon transection., Methods: Two subtypes of PSCs were derived from human adipose tissue: pericytes (CD146CD34CD45CD31) and adventitial cells (CD146CD34CD45CD31). Thirty-two athymic rats underwent right Achilles transection and were randomized to receive injection with saline (eight tendons), hydrogel (four tendons), pericytes in hydrogel (four tendons), or adventitial cells in hydrogel (eight tendons) 3 days postoperatively with the left serving as an uninjured control. Additionally, a subset of pericytes was labeled with CM-diI to track cell viability and localization. At 3 weeks, the rats were euthanized, and investigators blinded to treatment group allocation evaluated tendon healing by peak load and stiffness using biomechanical testing and percent area of collagen using histologic analysis with picrosirius red staining., Results: Histologic analysis showed a higher mean percent area collagen for pericytes (30%) and adventitial cells (28%) than hydrogel (21%) or saline (26%). However, a nonparametric statistical analysis yielded no statistical difference. Mechanical testing demonstrated that the pericyte group had a higher peak load than the saline group (41 ± 7 N versus 26 ± 9 N; mean difference 15 N; 95% confidence interval [CI], 4-27 N; p = 0.003) and a higher peak load than the hydrogel group (41 ± 7 N versus 25 ± 3 N; mean difference 16; 95% CI, 8-24 N; p = 0.001). The pericyte group demonstrated higher stiffness than the hydrogel group (36 ± 12 N/mm versus 17 ± 6 N/mm; mean difference 19 N/mm; 95% CI, 5-34 N/mm; p = 0.005)., Conclusions: Our results suggest that injection of PSCs improves mechanical but not the histologic properties of early Achilles tendon healing., Clinical Relevance: This is a preliminary study that provides more insight into the use of adipose-derived PSCs as a percutaneous therapy in the setting of Achilles tendon rupture. Further experiments to characterize the function of these cells may serve as a pathway to development of minimally invasive intervention aimed at improving nonoperative management while avoiding the complications associated with surgical treatment down the line.

Experimental search for high-temperature ferroelectric perovskites is a challenging task due to the vast chemical space and lack of predictive guidelines. Here, we demonstrate a two-step machine learning approach to guide experiments in search of xBi[Formula: see text]O 3 -(1 - x)PbTiO 3 -based perovskites with high ferroelectric Curie temperature. These involve classification learning to screen for compositions in the perovskite structures, and regression coupled to active learning to identify promising perovskites for synthesis and feedback. The problem is challenging because the search space is vast, spanning ~61,500 compositions and only 167 are experimentally studied. Furthermore, not every composition can be synthesized in the perovskite phase. In this work, we predict x, y, Me', and Me″ such that the resulting compositions have both high Curie temperature and form in the perovskite structure. Outcomes from both successful and failed experiments then iteratively refine the machine learning models via an active learning loop. Our approach finds six perovskites out of ten compositions synthesized, including three previously unexplored {Me'Me″} pairs, with 0.2Bi(Fe 0.12 Co 0.88 )O 3 -0.8PbTiO 3 showing the highest measured Curie temperature of 898 K among them.

Although methacrylic acid derivatives in their polymeric form are considered to be safe, insufficient polymerization and the release of monomers due to either mechanical or enzymatical factors can lead to their reaching millimolar concentrations in local tissue. The present study evaluates the effect of two methacrylate monomers - ethylene glycol dimethacrylate (EGDMA) and diethylene glycol dimethacrylate (DEGDMA) - on human gingival fibroblasts (HGFs). Both monomers were found to reduce cells viability in MTT assay, increase apoptosis and cause cell cycle arrest in G1/G0 phase. They also increased intracellular reactive oxygen species (ROS) production as measured by DCFH-DA and DHE probes and increased expression of GPx4 and SOD2. Both monomers increased DNA damage in comet assay. Moreover, HGFs were not able to repair those lesions within 120min of repair incubation. However, the monomers were not found to have any effect on the integrity of isolated plasmids. We postulate that EGDMA and DEGDMA exhibit their cytotoxic and genotoxic properties via increased production of ROS, which cause DNA damage, affect apoptosis, viability and cell cycle. Further studies are needed to better understand the properties of methacrylic acid monomers and to evaluate the risk that they cause for patients, dentists and dental technicians., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Land-use activities can alter hydrological and biogeochemical processes that can affect the fate, transformation, and transport of mercury (Hg). Previous studies in boreal forests have shown that forestry operations can have profound but variable effects on Hg export and methylmercury (MeHg) formation. The Pacific Northwest is an important timber producing region that receives large atmospheric Hg loads, but the impact of forest harvesting on Hg mobilization has not been directly studied and was the focus of our investigation. Stream discharge was measured continuously, and Hg and MeHg concentrations were measured monthly for 1.5 years following logging in three paired harvested and unharvested (control) catchments. There was no significant difference in particulate-bound Hg concentrations or loads in the harvested and unharvested catchments which may have resulted from forestry practices aimed at minimizing erosion. However, the harvested catchments had significantly higher discharge (32%), filtered Hg concentrations (28%), filtered Hg loads (80%), and dissolved organic carbon (DOC) loads (40%) compared to forested catchments. MeHg concentrations were low (mostly <0.05 ng L -1 ) in harvested, unharvested, and downstream samples due to well-drained/unsaturated soil conditions and steep slopes with high energy eroding stream channels that were not conducive to the development of anoxic conditions that support methylation. These results have important implications for the role forestry operations have in affecting catchment retention and export of Hg pollution.

Ipilimumab, an immune checkpoint inhibitor, is approved for treatment metastastic melanoma and is a promising agent against other malignancies. There is some preliminary evidence from case reports that ipilimumab treatment may be associated with pulmonary side effects. However, data from prospective studies on ipilimumab-related pulmonary toxicity are still scarce. Serial spirometries and measurements of CO-diffusion capacity (DLCO) in patients with metastatic melanoma before and during treatment with ipilimumab were performed. A reduction from baseline of forced vital capacity (FVC) of ≥ 10%, or ≥ 15% of DLCO was defined as clinically meaningful and indicative for pulmonary toxicity. Of 71 patients included in this study, a clinically meaningful lung function decline was registered in 6/65 (9%), 5/44 (11%), and 9/38 (24%) patients after 3, 6, and 9 weeks of treatment initiation, respectively. Even after adjusting for age, concomitant melanoma treatment, progressive pulmonary metastases, and baseline pulmonary function values, mean ± SD DLCO decreased significantly during follow-up (-4.3% ± 13.6% from baseline, p = 0.033). Only 7% of patients reported respiratory symptoms. Clinically manifest ipilimumab-related pneumonitis was diagnosed only in one patient (1.4%). DLCO decline maybe an early indicator of subclinical pulmonary drug toxicity. Therefore, routine pulmonary function testing including DLCO measurement during treatment might help for risk stratification to screen for ipilimumab-related pneumonitis.

The shape of liquid crystalline elastomers (LCEs) with spatial variation in the director orientation can be transformed by exposure to a stimulus. Here, informed by previously reported analytical treatments, we prepare complex spiral patterns imprinted into LCEs and quantify the resulting shape transformation. Quantification of the stimuli-induced shapes reveals good agreement between predicted and experimentally observed curvatures. We conclude this communication by reporting a design strategy to allow LCE films to be anchored at their external boundaries onto rigid substrates without incurring internal, mechanical-mismatch stresses upon actuation, a critical advance to the realization of shape transformation of LCEs in practical device applications.

Objective: Preserving soft and hard tissues after extraction and implant placement is crucial for anterior esthetics. This technique will show how the information gathered from a cone-beam computed tomography (CBCT) scan of the maxillary left central incisor and an intra-oral digital impression can be merged to fabricate a CAD/CAM crown-root matrix to be used as an immediate provisional restoration that mimics the natural anatomy., Clinical Considerations: Due to trauma, a left central incisor appeared to be fractured and was scheduled for extraction and implant placement. The crown-root configuration captured by the CBCT scan was merged with the digital files from an intra-oral digital impression. A CAD/CAM crown-root matrix was fabricated. Because the matrix shell was fabricated with the exact anatomy of the natural tooth, it replicated the position and three dimensional anatomy of the soft and hard tissue. It was connected to the implant with a customized provisional abutment. A digital impression of a coded healing abutment was made to fabricate the final implant abutment and final restoration. Throughout the treatment time and 36 months after completion, the thickness of tissue, emergence profile, and adjacent papilla was analyzed by clinical evaluation and photography and seemed to be maintained., Conclusion: The use of a pre-operative intra-oral digital scan of the clinical crown-root architecture and the CBCT scan of the bone/root anatomy, can be used together to fabricate a CAD/CAM crown-root form provisional matrix. This digital design helps in the preservation of the 3D tissue topography, as well as the final restoration., Clinical Significance: The preservation of soft and hard tissue after extraction and implant placement has always been paramount for ideal anterior implant esthetics. Using the information from digital files from CBCT scans and intra-oral scans may help the clinician identify critical anatomical features that can be replicated in the provisional and final CAD/CAM restoration. (J Esthet Restor Dent 29:13-21, 2017)., (© 2016 Wiley Periodicals, Inc.)

We present the studies of structural, transport and magnetotransport properties of [Formula: see text]Cd x GeAs 2 crystals with the chemical content changing from 0 to 1. The structural studies indicate that this alloy exists as a composite two-phase material in almost the entire range of average chemical compositions. The two phase nature of our samples does have a significant influence on the carrier transport and magnetotransport of the composite alloy. The change of the conductivity type is observed at room temperature, from p-type for [Formula: see text] to n-type for x  >  0.18, respectively. The Hall carrier mobility measured at room temperature decreases as a function of x from about 35 cm 2 (V · s) -1 for the sample with x  =  0 down to 3 cm 2 (V · s) -1 for the sample with x  =  0.233. For x  >  0.233 the Hall carrier mobility shows an increase with x, up to the highest value around 875 cm 2 (V · s) -1 observed for the sample with x  =  1. Temperature dependent resistivity measurements indicate the presence of thermal activation of carriers with activation energy, E a , with values from 20 to 30 meV for all the studied samples. The temperature dependent Hall effect data show that the grain boundary limited transport is strong in all our samples. For the samples with [Formula: see text] the negative MR is observed at temperatures lower than 100 K and at low magnetic field values, [Formula: see text] T. This effect is interpreted as a weak localization phenomenon with low values of phase coherence length, [Formula: see text] nm.

Since the advent of topological insulators hosting Dirac surface states, efforts have been made to gap these states in a controllable way. A new route to accomplish this was opened up by the discovery of topological crystalline insulators where the topological states are protected by crystal symmetries and thus prone to gap formation by structural changes of the lattice. Here we show a temperature-driven gap opening in Dirac surface states within the topological crystalline insulator phase in (Pb,Sn)Se. By using angle-resolved photoelectron spectroscopy, the gap formation and mass acquisition is studied as a function of composition and temperature. The resulting observations lead to the addition of a temperature- and composition-dependent boundary between massless and massive Dirac states in the topological phase diagram for (Pb,Sn)Se (001). Overall, our results experimentally establish the possibility to tune between massless and massive topological states on the surface of a topological system.

Analytical method for the determination of six flame retardants (FRs) from two groups was proposed. These groups included the brominated flame retardants (BFRs) 3,3',5,5'-tetrabromobisphenol A (TBBPA), 1,2,5,6,9,10-hexabromocyclododecane (HBCD) and tetrabromophthalic anhydride (TBPA) and triester organophosphate flame retardants (OPFRs) tris(2,3-dibromopropyl) phosphate (TBPP), ethylhexyl diphenyl phosphate (EHDP) and triphenyl phosphate (TPhP). Reversed phase ultrahigh-performance liquid chromatography (UHPLC) with a UV detector, different chromatographic columns, different mobile phases and gradient elution programmes were used to obtain the best separations within the shortest possible time. Solid-phase extraction (SPE) was examined as a pre-concentration step from distilled water. The column with the highest recoveries (the Bond Elut ENV column gave recoveries over 70 % for all compounds) was then tested on 1-L blank surface water samples. The proposed analytical procedure was applied for the determination of FRs in surface water samples. The concentrations of FRs found in water samples ranged from 0.03 (TPhP) to 3.10 μg L -1 (HBCD). Method detection limits (MDLs) ranged from 0.008 to 0.518 μg L -1 , and method quantification limits (MQLs) ranged from 0.023 to 1.555 μg L -1 for all compounds.

Chicken fat and sunflower oil 2:3 m/m blend was enzymatically interesterified at 60°C with and without microwaves assistance. As the catalyst a commercial preparation of the immobilized lipase from Rhizomucor miehei (Lipozyme RM IM) containing 2% of water was used, and the catalyst load was 8% in each case. The starting mixture and the interesterified products were separated by column chromatography into pure triacylglycerols fraction (TAG) and a non-triacylglycerol fraction, which contained free fatty acids (FFA), mono- and diacylglycerols (MAG and DAG). The oxidative stabilities (OS) of fats studied and TAG derived from them were assessed by Rancimat at 100°C and by Pressure Differential Scanning Calorimetry (PDSC) under oxygen at 110-140°C. Interesterification reduced the OS of chicken fat and sunflower oil blend. The main factors influenced on the OS of fats studied were concentrations of tocopherols and presence of FFA, MAG- and DAG. The structures of TAGs were of minor importance. From the resulting PDSC exotherms their times to reach the onset (τon) and peak maximum (τmax) were measured and used for calculations of parameters of the Arrhenius type kinetics for thermaloxidative decomposition of fats studied.

A mixture of lard and rapeseed oil (1:1, wt/wt) was interesterified using immobilized lipases from Rhizomucor miehei (Lipozyme RM IM) and Candida antarctica (Novozym 435) as catalysts. Enzymatic interesterifications were carried out at 60°C for 8 h with Lipozyme RM IM or at 80°C for 4 h with Novozym 435. The biocatalyst doses were kept constant (8 wt-%). The starting blend was quantitatively separated by column chromatography into pure triacylglycerol fraction (98.5%), and a nontriacylglycerol fraction containing free fatty acids (0.3%) and of mono- and diacylglycerols (1.2%). It was found that after interesterification the contents of free fatty acids and of mono- and diacylglycerols increased to 3.5% and 6.3% or to 1.5% and 4.5% when Lipozyme RM IM and Novozym 435 were used, respectively.The slip melting temperatures and solid fat contents of the triacylglycerol fractions separated from interesterified samples were lower compared with the nonesterified blend. The sn-2 and sn-1,3 distribution of fatty acids in the triacylglycerol fractions before and after interesterification were determined. The compositions of fatty acids at sn-2 were near statistical (33.3%) when Novozym 435 was used. When Lipozyme RM IM was used, the fatty acid compositions at the sn-2 position remained practically unchanged, compared with the starting blend. The changes in molecular structures of fat components due to interesterification have greatly influenced on the melting profiles of products as illustrated by the DSC melting scans. The interesterified fats and isolated triacylglycerols had reduced oxidative stabilities, as assessed by Dynamic DSC and Isothermal PDSC measurements. The Arrhenius kinetic parameters for fats oxidation based on DSC and PDSC measurements were calculated.

Topological insulators are a class of quantum materials in which time-reversal symmetry, relativistic effects and an inverted band structure result in the occurrence of electronic metallic states on the surfaces of insulating bulk crystals. These helical states exhibit a Dirac-like energy dispersion across the bulk bandgap, and they are topologically protected. Recent theoretical results have suggested the existence of topological crystalline insulators (TCIs), a class of topological insulators in which crystalline symmetry replaces the role of time-reversal symmetry in ensuring topological protection. In this study we show that the narrow-gap semiconductor Pb(1-x)Sn(x)Se is a TCI for x  =  0.23. Temperature-dependent angle-resolved photoelectron spectroscopy demonstrates that the material undergoes a temperature-driven topological phase transition from a trivial insulator to a TCI. These experimental findings add a new class to the family of topological insulators, and we anticipate that they will lead to a considerable body of further research as well as detailed studies of topological phase transitions.

A SPE-UHPLC-UV method for the determination of 13 pharmaceuticals from different therapeutic groups in surface water and wastewater samples was proposed. The following three solid-phase-extraction (SPE) columns with polymeric sorbents were used as a pre-concentration step: the Oasis HLB (average recoveries 93.8 %), the Nexus (84.0 %) and the Bond Elut ENV (88.3 %). A reverse-phase UHPLC with a C(18e) monolithic column and gradient elution program was used to obtain the best separations for all 13 drugs in short analysis time (3.4 min). The LOD range for determined drugs was 0.02-0.18 μg L(-1), and the concentration range for drugs found in water samples was 0.06-0.90 μg L(-1). The proposed method was used to analyze different water samples, mostly from rivers, and can be used as a monitoring tool for environmental pollution.

Primary hyperaldosteronism, one cause of which is aldosterone-producing adenomas (APAs), may account for ≤5% to 10% of cases of essential hypertension. Germline mutations have been identified in 2 rare familial forms of primary hyperaldosteronism, but it has been reported recently that somatic mutations of the KCNJ5 gene, which encodes a potassium channel, are present in some sporadic nonsyndromic APAs. To address this further we screened 2 large collections of sporadic APAs from the United Kingdom and Australia (totalling 73) and found somatic mutations in the selectivity filter of KCNJ5 in 41% (95% CI: 31% to 53%) of the APAs (30 of 73). These included the previously noted nonsynonymous mutations, G151R and L158R, and an unreported 3-base deletion, delI157, in the region of the selectivity filter. APAs containing a somatic KCNJ5 mutation were significantly larger than those without (1.61 cm [95% CI: 1.39-1.83 cm] versus 1.04 cm [95% CI: 0.91-1.17 cm]; P<0.0001) but with substantial overlap in size between genotypes. The APAs carrying a mutation, but not those without, also consistently lacked a postural aldosterone response, suggesting a physiologically distinct subtype. Hence, somatic KCNJ5 mutations are not restricted to large APAs (>2 cm), and their frequency in our unselected series suggests they are common and could be important in the molecular pathogenesis of many sporadic cases of APA.

Distal hereditary motor neuropathies comprise a clinically and genetically heterogeneous group of disorders. We recently mapped an X-linked form of this condition to chromosome Xq13.1-q21 in two large unrelated families. The region of genetic linkage included ATP7A, which encodes a copper-transporting P-type ATPase mutated in patients with Menkes disease, a severe infantile-onset neurodegenerative condition. We identified two unique ATP7A missense mutations (p.P1386S and p.T994I) in males with distal motor neuropathy in two families. These molecular alterations impact highly conserved amino acids in the carboxyl half of ATP7A and do not directly involve the copper transporter's known critical functional domains. Studies of p.P1386S revealed normal ATP7A mRNA and protein levels, a defect in ATP7A trafficking, and partial rescue of a S. cerevisiae copper transport knockout. Although ATP7A mutations are typically associated with severe Menkes disease or its milder allelic variant, occipital horn syndrome, we demonstrate here that certain missense mutations at this locus can cause a syndrome restricted to progressive distal motor neuropathy without overt signs of systemic copper deficiency. This previously unrecognized genotype-phenotype correlation suggests an important role of the ATP7A copper transporter in motor-neuron maintenance and function., (Copyright 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

A cocoa butter (CB)-like fat was produced in a packed bed enzyme reactor using sn-1,3 specific lipase, and its blends with CB were prepared at different ratios (CB: CB-like fat; 100: 0, 90: 10, 80: 20, 70: 30, 60: 40, 50: 50, 0: 100). The oxidation kinetics of CB: CB-like fat blends was studied by differential scanning calorimeter (DSC). Samples were heated in DSC at different temperatures (130, 140, 150, 160 degrees C) under 100 mL/min oxygen. From DSC exotherms, oxidation induction times (OIT) were determined and used for the assessment of the oxidative stabilities of the blends. Oxidation kinetics parameters (activation energy, E(a); preexponential factor, Z; and oxidation rate constant, k) were calculated. In general, it has been observed that above 110 degrees C increasing the ratio of CB-like fat in the blend increased the k value with increasing temperature. It has been observed that for all blends the increase in k value with temperature was significant (P < 0.05). Increasing CB-like fat ratio in the blend decreased the content of major TAGs (1,3-dipalmitoyl-2-oleoyl-glycerol [POP]; 1[3]-palmitoyl-3[1]stearoyl-2-oleoyl-glycerol [POS]; 1,3-distearoyl-2-oleoyl-glycerol [SOS]), and decreased the oxidative stability of the blends.

Objective: To clinically characterize and map the gene locus in a three-generation family with an X-linked adult-onset distal hereditary motor neuropathy., Methods: Microsatellite markers spanning the juvenile distal spinal muscular atrophy (DSMAX) locus were genotyped and analyzed using genetic linkage analysis. The promoter, untranslated and coding region of the gap junction beta1 (GJB1) gene was sequenced. Nine positional candidate genes were screened for disease mutations using high-resolution melt (HRM) analysis., Results: The family showed significant linkage to markers on chromosome Xq13.1-q21. Haplotype construction revealed a disease-associated haplotype between the markers DXS991 and DX5990. Sequence analysis excluded pathogenic changes in the coding and promoter regions of the GJB1 gene. Additional fine mapping in the family refined the DSMAX locus to a 1.44-cM interval between DXS8046 and DXS8114. HRM analysis did not identify disease-associated mutations in the coding region of nine candidate genes., Conclusion: We have identified a family with adult-onset distal hereditary motor neuropathy that refines the locus reported for juvenile distal spinal muscular atrophy (DSMAX) on chromosome Xq13.1-q21. Exclusion of mutations in the coding and regulatory region of the GJB1 gene eliminated the CMTX1 locus as a cause of disease in this family. Nine positional candidate genes in the refined interval underwent mutation analysis and were eliminated as the pathogenic cause of DSMAX in this family. The syndrome in this family may be allelic to the juvenile distal spinal muscular atrophy first reported at this locus.