Association of fetal hemoglobin level with frequency of acute pain episodes in sickle cell disease (HbS-only phenotype) patients.

BACKGROUND: Sickle cell disease (SCD) is a Mendelian single gene disorder with highly variable phenotypic expression. In the present study, we analyzed the influence of HbF, alpha thalassemia and other hematological indices to determine their association with acute pain episodes. METHOD: This case control study consisted of SCD subjects with HbS phenotype experiencing three or more acute pain episodes in last twelve months (cases) and without any episode of acute pain during last twelve months (controls). Hematological parameters, HbF, and presence of alpha thalassemia were assessed in all subjects. RESULTS: A statistically significant difference between HbF levels (P < 0.025, χ2 test) and alpha thalassemia (P < 0.008, χ2 test) was observed between controls and cases group. Univariate analysis indicated that increased HbF levels > 25% (OR: 0.37, 95% CI: 0.18-0.77, P < 0.008) and presence of alpha thalassemia (OR: 0.53, 95% CI: 0.33-0.85, P < 0.009) provided protection, while multivariate analysis revealed significant protection was attributable only by higher HbF levels (OR: 0.39, 95% CI: 0.17-0.88, P < 0.025). Significantly higher HbF levels were observed only in the 11-20 age group of cases in comparison to controls (Student's t-test, P < 0.001). CONCLUSION: Higher concentrations of HbF are associated with protection against frequent episodes of acute pain crisis in SCD patients.

Ambient electrospray deposition Raman spectroscopy (AESD RS) using soft landed preformed silver nanoparticles for rapid and sensitive analysis.

We introduce a technique called ambient electrospray deposition Raman spectroscopy (AESD RS) for rapid and sensitive surface-enhanced Raman scattering (SERS) based detection of analytes using a miniature Raman spectrometer. Using electrospray, soft landing of preformed silver nanoparticles (AgNPs) was performed for 30-40 seconds for different concentrations of analytes deposited on conducting glass slides. Using AESD RS, SERS signals were collected within 4-6 minutes, including sample preparation. Transmission electron microscopy (TEM) and dark-field microscopy (DFM) were used to characterize the preformed AgNPs before and after electrospray. We achieved the nanomolar and micromolar detection of p-mercaptobenzoic acid (p-MBA) and 2,4-dinitrotoluene (2,4-DNT), respectively. In this work, 0.3 µL of preformed AgNPs were used, which is ∼33 times less in volume than the quantity needed for conventional SERS. Quantitation of unknown concentration of analytes was also possible. A similar amount of electrosprayed AgNPs was utilized to characterize Escherichia coli (E. coli) bacteria of different concentrations. Viability of bacteria was tested using fluorescence microscopic imaging. Besides reduced analysis time and improved reproducibility of the data in every analysis, which is generally difficult in SERS, the amount of AgNPs required is an order of magnitude lower in this method. This method could also be used to probe the real-time changes in molecular and biological species under ambient conditions.

Erythrocyte cAMP in Determining Frequency of Acute Pain Episodes in Sickle Cell Disease Patients from Odisha State, India.

Vaso-occlusive crisis (VOC) occurs more frequently during stress in sickle cell disease patients. Epinephrine released during stress increases adhesion of sickled red blood cells (RBCs) to endothelium and to leukocytes, a process mediated through erythrocyte cyclic adenosine monophosphate (cAMP). Increased adhesion of sickled RBCs retards blood flow through the capillaries and promotes vaso-occlusion. Therefore, we examined the association of RBC-cAMP levels with frequency of acute pain episodes in sickle cell disease subjects. Using a case control study design, we measured RBC-cAMP levels, fetal hemoglobin (Hb F), α-thalassemia (α-thal) and other hematological parameters at baseline (sham treated) and after stimulation with epinephrine. The cases consisted of sickle cell disease subjects with three or more acute pain episodes in the last 12 months, and those without a single acute pain episode in the last 12 months were considered as controls. Significantly higher cAMP values were found in cases than the controls, in both sham treated (p < 0.001) and epinephrine treated RBCs (p < 0.001) by Wilcoxon Rank Sum test. However, significant association of cAMP values was observed both on univariate [odds ratio (OR): 4.8, 95% confidence interval (95% CI): 1.51-15.19, p < 0.008) and multivariate logistic regression analyses only in epinephrine treated (OR: 5.07, 95% CI: 1.53-16.82, p < 0.008) but not in sham-treated RBCs. In the covariates, Hb F consistently showed protective effects in univariate as well as in multivariate analyses. Frequent acute pain episodes are associated with higher cAMP levels than those with less frequent pain episodes, only after stimulation with epinephrine but not with baseline level.

Association between unhygienic menstrual management practices and prevalence of lower reproductive tract infections: a hospital-based cross-sectional study in Odisha, India.

BACKGROUND: The extent to which reproductive tract infections (RTIs) are associated with poor menstrual hygiene management (MHM) practices has not been extensively studied. We aimed to determine whether poor menstrual hygiene practices were associated with three common infections of the lower reproductive tract; Bacterial vaginosis (BV), Candida, and Trichomonas vaginalis (TV). METHODS: Non-pregnant women of reproductive age (18-45 years) and attending one of two hospitals in Odisha, India, between April 2015 and February 2016 were recruited for the study. A standardized questionnaire was used to collect information on: MHM practices, clinical symptoms for the three infections, and socio-economic and demographic information. Specimens from posterior vaginal fornix were collected using swabs for diagnosis of BV, Candida and TV infection. RESULTS: A total of 558 women were recruited for the study of whom 62.4% were diagnosed with at least one of the three tested infections and 52% presented with one or more RTI symptoms. BV was the most prevalent infection (41%), followed by Candida infection (34%) and TV infection (5.6%). After adjustment for potentially confounding factors, women diagnosed with Candida infection were more likely to use reusable absorbent material (aPRR = 1.54, 95%CI 1.2-2.0) and practice lower frequency of personal washing (aPRR = 1.34, 95%CI 1.07-1.7). Women with BV were more likely to practice personal washing less frequently (aPRR = 1.25, 95%CI 1.0-1.5), change absorbent material outside a toilet facility (aPRR = 1.21, 95%CI 1.0-1.48) whilst a higher frequency of absorbent material changing was protective (aPRR = 0.56, 95%CI 0.4-0.75). No studied factors were found to be associated with TV infection. In addition, among women reusing absorbent material, Candida but not BV or TV - infection was more frequent who dried their pads inside their houses and who stored the cloth hidden in the toilet compartment. CONCLUSION: The results of our study add to growing number of studies which demonstrate a strong and consistent association between poor menstrual hygiene practices and higher prevalence of lower RTIs.

Higher vaginal pH in Trichomonas vaginalis infection with intermediate Nugent score in reproductive-age women-a hospital-based cross-sectional study in Odisha, India.

A close association between Trichomonas vaginalis (TV) infection and bacterial vaginosis (BV) has been reported. Some other studies have found association is stronger with intermediate Nugent score than BV. Most studies have used wet mount microscopy, a relatively insensitive method, to detect TV infection. We wanted to study the association of TV infection with BV and with intermediate Nugent score. We undertook a cross-sectional hospital-based study of 1110 non-pregnant women from Odisha state, India, aged between 18 and 45 years, collecting vaginal swabs for diagnosis of BV by Nugent score (NS) criteria and TV by PCR analysis. TV infection was found in 13.3% of women with intermediate Nugent score (NS 4-6) and 13.6% with BV (NS 7-10). Before adjustment, TV infection was associated with BV, intermediate Nugent, vaginal pH ≥ 4.5, and age group between 26 and 35 years. Multivariate analysis confirmed that TV infection was more likely to have raised vaginal pH, either BV or intermediate Nugent. Proportion of TV cases increased sequentially with the increase in Nugent score up to NS 6, after which a decline was observed. Vaginal pH was higher in the TV-infected group than the uninfected group in women with intermediate Nugent, but no difference was noticed in women with BV. TV infection was equally prevalent in women with intermediate Nugent as well as BV. In the intermediate Nugent group women, TV infection was found only when vaginal pH was raised, indicating a crucial role of vaginal pH in determining TV infection.

Dichroic coherent diffractive imaging.

Understanding electronic structure at the nanoscale is crucial to untangling fundamental physics puzzles such as phase separation and emergent behavior in complex magnetic oxides. Probes with the ability to see beyond surfaces on nanometer length and subpicosecond time scales can greatly enhance our understanding of these systems and will undoubtedly impact development of future information technologies. Polarized X-rays are an appealing choice of probe due to their penetrating power, elemental and magnetic specificity, and high spatial resolution. The resolution of traditional X-ray microscopes is limited by the nanometer precision required to fabricate X-ray optics. Here we present a novel approach to lensless imaging of an extended magnetic nanostructure, in which a scanned series of dichroic coherent diffraction patterns is recorded and numerically inverted to map its magnetic domain configuration. Unlike holographic methods, it does not require a reference wave or precision optics. In addition, it enables the imaging of samples with arbitrarily large spatial dimensions, at a spatial resolution limited solely by the coherent X-ray flux, wavelength, and stability of the sample with respect to the beam. It can readily be extended to nonmagnetic systems that exhibit circular or linear dichroism. We demonstrate this approach by imaging ferrimagnetic labyrinthine domains in a Gd/Fe multilayer with perpendicular anisotropy and follow the evolution of the domain structure through part of its magnetization hysteresis loop. This approach is scalable to imaging with diffraction-limited resolution, a prospect rapidly becoming a reality in view of the new generation of phenomenally brilliant X-ray sources.

Proton-Gated Synaptic Transistors, Based on an Electron-Beam Patterned Nafion Electrolyte.

Neuromorphic processors using artificial neural networks are the center of attention for energy-efficient analog computing. Artificial synapses act as building blocks in such neural networks for parallel information processing and data storage. Herein we describe the fabrication of a proton-gated synaptic transistor using a Nafion electrolyte thin film, which is patterned by electron-beam lithography (EBL). The device has an active channel of indium-zinc-oxide (IZO) between the source and drain electrodes, which shows Ohmic behavior with a conductance level on the order of 100 µS. Under voltage applications to the gate electrode, the channel conductance is changed due to the injection and extraction of protons between the IZO channel and the Nafion electrolyte, emulating various synaptic functions with short-term and long-term plasticity. When positive (negative) gate voltage pulses are consecutively applied, the device exhibits long-term potentiation (depression) at the same number of steps as the number of input pulses. Based on these characteristics, an artificial neural network using this transistor shows ∼84% image recognition accuracy for handwritten digits. The subject transistor also successfully mimics paired-pulse facilitation and depression, Hebbian spike-timing-dependent plasticity, and Pavlovian associative learning followed by extinction activities. Finally, dynamical pattern image memorization is demonstrated in a 5 × 5 array of these synaptic transistors. The results indicate that EBL patternable Nafion electrolytes have great potential for use in the fabrication and circuit-level integration of synaptic devices for neuromorphic computing applications.

Correction: Secondary ligand-induced orthogonal self-assembly of silver nanoclusters into superstructures with enhanced NIR emission.

Correction for 'Secondary ligand-induced orthogonal self-assembly of silver nanoclusters into superstructures with enhanced NIR emission' by Korath Shivan Sugi, et al., Nanoscale, 2023, https://doi.org/10.1039/d3nr02561f.

Secondary ligand-induced orthogonal self-assembly of silver nanoclusters into superstructures with enhanced NIR emission.

Orthogonal self-assembly is one of the crucial strategies for forming complex and hierarchical structures in biological systems. However, creating such ordered complex structures using synthetic nanoparticles is a challenging task and requires a high degree of control over structure and multiple non-covalent interactions. In this context, nanoarchitectonics serves as an emerging tool to fabricate complex functional materials. Here, we present a secondary ligand-induced orthogonal self-assembly of atomically precise silver nanoclusters into complex superstructures. Specifically, we use Ag14NCs protected with naphthalene thiol and 1,6-bis(diphenylphosphino)hexane ligands. Controlled addition of 1,6-bis(diphenylphosphino)hexane, the secondary ligand resulted in a self-assembled supracolloidal structure including helical fibers, spheres, and nanosheets. The self-assembly process is tunable by controlling the molar ratio of the ligand. The resulting superstructures exhibit enhanced NIR emission due to restricted intramolecular motion. This demonstrates that by tuning supramolecular interactions, hierarchical nanostructures with desired properties similar to biomolecules can be obtained from atomically precise building blocks.

Method for single-shot coherent diffractive imaging of magnetic domains.

In preparation for real space studies of magnetic domains in a pump-probe setup at free-electron laser sources, it is necessary to develop an imaging method compatible with the linearly polarized radiation available at these sources. We present results from a prototype experiment performed at the synchrotron source BESSY II, using a modification of existing phase retrieval techniques. Our results show that it is possible to image magnetic domains in real space using linear polarized light, and we introduce the concept of a reliability map of our reconstructions using Gabor transforms.

Femtosecond single-shot imaging of nanoscale ferromagnetic order in Co/Pd multilayers using resonant x-ray holography.

We present the first single-shot images of ferromagnetic, nanoscale spin order taken with femtosecond x-ray pulses. X-ray-induced electron and spin dynamics can be outrun with pulses shorter than 80 fs in the investigated fluence regime, and no permanent aftereffects in the samples are observed below a fluence of 25 mJ/cm(2). Employing resonant spatially muliplexed x-ray holography results in a low imaging threshold of 5 mJ/cm(2). Our results open new ways to combine ultrafast laser spectroscopy with sequential snapshot imaging on a single sample, generating a movie of excited state dynamics.

Understanding the Magnetic Microstructure through Experiments and Machine Learning Algorithms.

Advanced machine learning techniques have unfurled their applications in various interdisciplinary areas of research and development. This paper highlights the use of image regression algorithms based on advanced neural networks to understand the magnetic properties directly from the magnetic microstructure. In this study, Co/Pd multilayers have been chosen as a reference material system that displays maze-like magnetic domains in pristine conditions. Irradiation of Ar+ ions with two different energies (50 and 100 keV) at various fluences was used as an external perturbation to investigate the modification of magnetic and structural properties from a state of perpendicular magnetic anisotropy to the vicinity of the spin reorientation transition. Magnetic force microscopy revealed domain fragmentation with a smaller periodicity and weaker magnetic contrast up to the fluence of 1014 ions/cm2. Further increases in the ion fluence result in the formation of feather-like domains with a variation in local magnetization distribution. The experimental results were complemented with micromagnetic simulations, where the variations of effective magnetic anisotropy and exchange constant result in qualitatively similar changes in magnetic domains, as observed experimentally. Importantly, a set of 960 simulated domain images was generated to train, validate, and test the convolutional neural network (CNN) that predicts the magnetic properties directly from the domain images with a high level of accuracy (maximum 93.9%). Our work has immense importance in promoting the applications of image regression methods through the CNN in understanding integral magnetic properties obtained from the microscopic features subject to change under external perturbations.

Gold cluster-loaded dendritic nanosilica: single particle luminescence and catalytic properties in the bulk.

We report a hybrid material in which surface anchoring-induced enhanced luminescence of AuQC@BSA clusters on high surface area dendritic fibrous nanosilica of 800 nm diameter enabled their luminescence imaging at a single particle level. The photophysical and structural properties of the hybrid material were characterized by various spectroscopic and microscopic techniques. Concomitant imaging using scattering and luminescence of such mesostructures and their response to analytes have been used to develop a chemical sensor. The hybrid material was found to be catalytically active in silane to silanol conversion, and 100% conversion was observed in 4 h when the reaction was carried out at 30 °C in the presence of light. Such materials at submicron dimensions with enhanced surface area, emission in the solid state along with a high quantum yield of 12% in water along with enhanced scattering, and surface functionalities present numerous benefits for the creation of multifunctional materials.

Atom transfer between precision nanoclusters and polydispersed nanoparticles: a facile route for monodisperse alloy nanoparticles and their superstructures.

Reactions between atomically precise noble metal nanoclusters (NCs) have been studied widely in the recent past, but such processes between NCs and plasmonic nanoparticles (NPs) have not been explored earlier. For the first time, we demonstrate spontaneous reactions between an atomically precise NC, Au25(PET)18 (PET = 2-phenylethanethiol), and polydispersed silver NPs with an average diameter of 4 nm and protected with PET, resulting in alloy NPs under ambient conditions. These reactions were specific to the nature of the protecting ligands as no reaction was observed between the Au25(SBB)18 NC (SBB = 4-(tert-butyl)benzyl mercaptan) and the very same silver NPs. The mechanism involves an interparticle exchange of the metal and ligand species where the metal-ligand interface plays a vital role in controlling the reaction. The reaction proceeds through transient Au25-xAgx(PET)n alloy cluster intermediates as observed in time-dependent electrospray ionization mass spectrometry (ESI MS). High-resolution transmission electron microscopy (HRTEM) analysis of the resulting dispersion showed the transformation of polydispersed silver NPs into highly monodisperse gold-silver alloy NPs which assembled to form 2-dimensional superlattices. Using NPs of other average sizes (3 and 8 nm), we demonstrated that size plays an important role in the reactivity as observed in ESI MS and HRTEM.

Highly Sensitive As3+ Detection Using Electrodeposited Nanostructured MnOx and Phase Evolution of the Active Material during Sensing.

A simple, one-step electrodeposition approach has been used to fabricate MnOx on an indium-doped tin oxide substrate for highly sensitive As3+ detection. We report an experimental limit of detection of 1 ppb through anodic stripping voltammetry with selectivity to As3+ in the presence of 10 times higher concentrations of several metal ions. Additionally, we report the simultaneous phase evolution of active material occurring through multiple stripping cycles, wherein MnO/Mn2O3 eventually converts to Mn3O4 as a result of change in the oxidation states of manganese. This occurs with concomitant changes in morphology. Change in the electronic property (increased charge transfer resistance) of the material due to sensing results in an eventual decrease in sensitivity after multiple stripping cycles. In a nutshell, this paper reports stripping-voltammetry-induced change in morphology and phase of as-prepared Mn-based electrodes during As sensing.

A microscopic view on acoustomigration.

Stress-induced material transport in surface acoustic wave devices, so-called acoustomigration, is a prominent failure mechanism, especially in high-power applications. We used scanning probe microscopy techniques to study acoustomigration of metal structures in-situ, i.e., during the high-power loading of the device. Scanning acoustic force microscopy (SAFM) allows for the simultaneous measurement of the acoustic wavefield and the topography with submicron lateral resolution. High-resolution microscopy is essential as acoustomigration is a phenomenon that not only results in the formation of more macroscopic voids and hillocks but also affects the microscopic grain structure of the film. We present acoustic wavefield and topographic image sequences giving a clear insight into the nature of the film damage on a submicron scale. The 900 MHz test structures were fabricated on 36 degrees YX-lithium tantalate (YX-LiTaO3) and incorporated 420-nm thick aluminium (Al) electrodes. By correlating the acoustic wavefield mapping and the local changes in topography, we confirmed model calculations that predict the correspondence of damage and stress (i.e., hillocks and voids) are preferentially formed in areas of high stress. The way the film is damaged does not significantly depend on the applied power (for typical power levels used in this study). Furthermore, acoustomigration leads to smoother surfaces via lateral grain growth. Another contribution to the grain dynamics comes from the apparent grain rotation in the highly anisotropic stress field of an acoustic wave. Thus, through in-situ scanning probe microscopy techniques, one can observe the initial changes of the grain structure in order to obtain a more detailed picture of the phenomenon of acoustomigration.

Luminescent, bimetallic AuAg alloy quantum clusters in protein templates.

We report the synthesis of luminescent AuAg alloy quantum clusters (QCs) in bovine serum albumin (BSA), for the first time, with experimentally determined atomic composition. Mixing of the as-synthesized protein-protected Au and Ag clusters resulted in the formation of alloy AuAg clusters within the BSA. Mass spectrometric analysis of the product of a 1 : 1 molar ratio reaction mixture of Au(QC)@BSA and Ag(QC)@BSA suggested that the alloy clusters could be Au(38-x)Ag(x)@BSA. Further analyses by standard techniques revealed that the alloy cluster core of ∼1.2 nm diameter is composed of nearly zero valent Au and Ag atoms that exhibit distinctly different steady state and time resolved excited state luminescence profiles compared to the parent clusters. Tuning of the alloy composition was achieved by varying the molar ratio of the parent species in the reaction mixture and compositional changes were observed by mass spectrometry. In another approach, mixing of Au(3+) ions with the as-synthesized Ag(QC)@BSA also resulted in the formation of alloy clusters through galvanic exchange reactions. We believe that alloy clusters with the combined properties of the constituents in versatile protein templates would have potential applications in the future. The work presents interesting aspects of the reactivity of the protein-protected clusters.