Impact of COVID-19 on Guillain-Barre Syndrome in India: A Multicenter Ambispective Cohort Study.

Introduction/Aims: Studies conducted during the coronavirus disease 2019 (COVID-19) pandemic have reported varied data regarding the incidence of Guillain-Barre syndrome (GBS). The present study investigated demographic and clinical features, management, and outcomes of patients with GBS during a specified period of the COVID-19 pandemic, and compared these features to those of GBS in the previous year. Methods: A multicenter, ambispective cohort study including 26 centers across India was conducted. Data from a pre-COVID-19 period (March 1 to August 31, 2019) were collected retrospectively and collected ambispectively for a specified COVID-19 period (March 1 to August 31, 2020). The study was registered with the Clinical Trial Registry India (CTRI/2020/11/029143). Results: Data from 555 patients were included for analysis: pre-COVID-19 (n = 334) and COVID-19 (n = 221). Males were more commonly affected during both periods (male:female, 2:1). Gastroenteritis was the most frequent antecedent event in 2019 (17.4%), whereas fever was the most common event in 2020 (10.7%). Paraparesis (21.3% versus [vs.] 9.3%, P = 0.001) and sensory involvement (51.1% vs. 41.3%; P = 0.023) were more common during COVID-19 in 2020, whereas back pain (26.3% vs. 18.4%; P = 0.032) and bowel symptoms (20.7% vs. 13.7%; P = 0.024) were more frequent in the pre-COVID period. There was no difference in clinical outcomes between the two groups in terms of GBS disability score at discharge and 3 months after discharge. Independent predictors of disability in the pre-COVID period included areflexia/hyporeflexia, the requirementfor intubation, and time to bulbar weakness; in the COVID-19 period, independent predictors included time from onset to admission, intubation, and intubation requirement. The mortality rate was 2.3% during the entire study period (13/555 cases). Discussion: Results of this study revealed an overall reduction in the frequency of GBS during the pandemic. The lockdown likely reduced the risk for antecedent infections due to social distancing and improved hygiene, which may have resulted in the reduction of the frequency of GBS.

Probing spin correlations using angle-resolved photoemission in a coupled metallic/Mott insulator system.

A nearly free electron metal and a Mott insulating state can be thought of as opposite ends of the spectrum of possibilities for the motion of electrons in a solid. Understanding their interaction lies at the heart of the correlated electron problem. In the magnetic oxide metal PdCrO2, nearly free and Mott-localized electrons exist in alternating layers, forming natural heterostructures. Using angle-resolved photoemission spectroscopy, quantitatively supported by a strong coupling analysis, we show that the coupling between these layers leads to an "intertwined" excitation that is a convolution of the charge spectrum of the metallic layer and the spin susceptibility of the Mott layer. Our findings establish PdCrO2 as a model system in which to probe Kondo lattice physics and also open new routes to use the a priori nonmagnetic probe of photoemission to gain insights into the spin susceptibility of correlated electron materials.

Maximal Rashba-like spin splitting via kinetic-energy-coupled inversion-symmetry breaking.

Engineering and enhancing the breaking of inversion symmetry in solids-that is, allowing electrons to differentiate between 'up' and 'down'-is a key goal in condensed-matter physics and materials science because it can be used to stabilize states that are of fundamental interest and also have potential practical applications. Examples include improved ferroelectrics for memory devices and materials that host Majorana zero modes for quantum computing. Although inversion symmetry is naturally broken in several crystalline environments, such as at surfaces and interfaces, maximizing the influence of this effect on the electronic states of interest remains a challenge. Here we present a mechanism for realizing a much larger coupling of inversion-symmetry breaking to itinerant surface electrons than is typically achieved. The key element is a pronounced asymmetry of surface hopping energies-that is, a kinetic-energy-coupled inversion-symmetry breaking, the energy scale of which is a substantial fraction of the bandwidth. Using spin- and angle-resolved photoemission spectroscopy, we demonstrate that such a strong inversion-symmetry breaking, when combined with spin-orbit interactions, can mediate Rashba-like spin splittings that are much larger than would typically be expected. The energy scale of the inversion-symmetry breaking that we achieve is so large that the spin splitting in the CoO2- and RhO2-derived surface states of delafossite oxides becomes controlled by the full atomic spin-orbit coupling of the 3d and 4d transition metals, resulting in some of the largest known Rashba-like spin splittings. The core structural building blocks that facilitate the bandwidth-scaled inversion-symmetry breaking are common to numerous materials. Our findings therefore provide opportunities for creating spin-textured states and suggest routes to interfacial control of inversion-symmetry breaking in designer heterostructures of oxides and other material classes.

Noninvasive assessment of cutaneous alterations in mice exposed to whole body gamma irradiation using optical imaging techniques.

We report the results of a study carried out to investigate the potential of optical techniques such as optical coherence tomography, Mueller matrix spectroscopy, and cross-polarization imaging for noninvasive monitoring of the ionizing radiation exposure-induced alterations in cutaneous tissue of mice. Radiation dose-dependent changes were observed in tissue microvasculature and tissue optical parameters like retardance and depolarization as early as 1 h post radiation exposure. Results suggest that these optical techniques may allow early detection of radiation dose-dependent alterations which could help in screening of population exposed to radiation.

ARPES view on surface and bulk hybridization phenomena in the antiferromagnetic Kondo lattice CeRh2Si2.

The hybridization between localized 4f electrons and itinerant electrons in rare-earth-based materials gives rise to their exotic properties like valence fluctuations, Kondo behaviour, heavy-fermions, or unconventional superconductivity. Here we present an angle-resolved photoemission spectroscopy (ARPES) study of the Kondo lattice antiferromagnet CeRh2Si2, where the surface and bulk Ce-4f spectral responses were clearly resolved. The pronounced 4f (0) peak seen for the Ce terminated surface gets strongly suppressed in the bulk Ce-4f spectra taken from a Si-terminated crystal due to much larger f-d hybridization. Most interestingly, the bulk Ce-4f spectra reveal a fine structure near the Fermi edge reflecting the crystal electric field splitting of the bulk magnetic 4f (1)5/2 state. This structure presents a clear dispersion upon crossing valence states, providing direct evidence of f-d hybridization. Our findings give precise insight into f-d hybridization penomena and highlight their importance in the antiferromagnetic phases of Kondo lattices.

A rare case of vulval pilonidal sinus: incidental diagnosis.

A 63-year-old woman presented with a 4-week history of vulval bleeding. On examination, an 8 mm fleshy irregular vascular lesion was present on the vulva in the periclitoreal area. This vulval lesion was treated by surgical excision. Histological analysis showed irregular pieces of skin partly covered by hyperplastic squamous epithelium. There were areas of fistulous-like endophytic proliferations lined by hyperplastic squamous epithelial cells. The intervening stroma showed granulation tissue with severe active chronic inflammation. At least five hair follicle shafts surrounded by foreign body type giant cells were also identified within the inflamed area. There was no evidence of dysplasia or malignancy. This chronically inflamed fistulous tract together with hair shafts within the wall of the tract were diagnostic of a pilonidal sinus of the vulva. This case report summarises the importance of diagnosing pilonidal sinus at an unusual location.

A novel therapeutic approach with Caviunin-based isoflavonoid that en routes bone marrow cells to bone formation via BMP2/Wnt-ß-catenin signaling.

Recently, we reported that extract of Dalbergia sissoo made from leaves and pods have antiresorptive and bone-forming effects. The positive skeletal effect attributed because of active molecules present in the extract of Dalbergia sissoo. Caviunin 7-O-[ß-D-apiofuranosyl-(1-6)-ß-D-glucopyranoside] (CAFG), a novel isoflavonoid show higher percentage present in the extract. Here, we show the osteogenic potential of CAFG as an alternative for anabolic therapy for the treatment of osteoporosis by stimulating bone morphogenetic protein 2 (BMP2) and Wnt/ß-catenin mechanism. CAFG supplementation improved trabecular micro-architecture of the long bones, increased biomechanical strength parameters of the vertebra and femur and decreased bone turnover markers better than genistein. Oral administration of CAFG to osteopenic ovariectomized mice increased osteoprogenitor cells in the bone marrow and increased the expression of osteogenic genes in femur and show new bone formation without uterine hyperplasia. CAFG increased mRNA expression of osteoprotegerin in bone and inhibited osteoclast activation by inhibiting the expression of skeletal osteoclastogenic genes. CAFG is also an effective accelerant for chondrogenesis and has stimulatory effect on the repair of cortical bone after drill-hole injury at the tissue, cell and gene level in mouse femur. At cellular levels, CAFG stimulated osteoblast proliferation, survival and differentiation. Signal transduction inhibitors in osteoblast demonstrated involvement of p-38 mitogen-activated protein kinase pathway stimulated by BMP2 to initiate Wnt/ß-catenin signaling to reduce phosphorylation of GSK3-ß and subsequent nuclear accumulation of ß-catenin. Osteogenic effects were abrogated by Dkk1, Wnt-receptor blocker and FH535, inhibitor of TCF-complex by reduction in ß-catenin levels. CAFG modulated MSC responsiveness to BMP2, which promoted osteoblast differentiation via Wnt/ß-catenin mechanism. CAFG at 1 mg/kg(/)day dose in ovariectomy mice (human dose ∼0.081 mg/kg) led to enhanced bone formation, reduced bone resorption and bone turnover better than well-known phytoestrogen genistein. Owing to CAFG's inherent properties for bone, it could be positioned as a potential drug, food supplement, for postmenopausal osteoporosis and fracture repair.

Effect of gold nanoparticles on depolarization characteristics of Intralipid tissue phantom.

We report results of studies on the effect of different shapes and sizes of gold nanoparticles (GNPs) on the depolarization characteristics of Intralipid tissue phantoms. For a given extinction coefficient, the absorption characteristics of the GNPs contributed more to the depolarization of the turbid medium, and the contribution of scattering was significant only for the larger-sized particles. For rod-shaped GNPs, their depolarization plays an important role in the low scattering regime in which the depolarization properties of the nanoparticles (NPs) dominate in the turbid medium even if the contribution of the scattering from the NPs is about an order of magnitude less. For highly scattering samples, GNP absorption significantly modulates the depolarization spectra of the turbid medium.

Withaferin A: a proteasomal inhibitor promotes healing after injury and exerts anabolic effect on osteoporotic bone.

Withania somnifera or Ashwagandha is a medicinal herb of Ayurveda. Though the extract and purified molecules, withanolides, from this plant have been shown to have different pharmacological activities, their effect on bone formation has not been studied. Here, we show that one of the withanolide, withaferin A (WFA) acts as a proteasomal inhibitor (PI) and binds to specific catalytic ß subunit of the 20S proteasome. It exerts positive effect on osteoblast by increasing osteoblast proliferation and differentiation. WFA increased expression of osteoblast-specific transcription factor and mineralizing genes, promoted osteoblast survival and suppressed inflammatory cytokines. In osteoclast, WFA treatment decreased osteoclast number directly by decreasing expression of tartarate-resistant acid phosphatase and receptor activator of nuclear factor kappa-B (RANK) and indirectly by decreasing osteoprotegrin/RANK ligand ratio. Our data show that in vitro treatment of WFA to calvarial osteoblast cells decreased expression of E3 ubiquitin ligase, Smad ubiquitin regulatory factor 2 (Smurf2), preventing degradation of Runt-related transcription factor 2 (RunX2) and relevant Smad proteins, which are phosphorylated by bone morphogenetic protein 2. Increased Smurf2 expression due to exogenous treatment of tumor necrosis factor α (TNFα) to primary osteoblast cells was decreased by WFA treatment. This was corroborated by using small interfering RNA against Smurf2. Further, WFA also blocked nuclear factor kappa-B (NF-kB) signaling as assessed by tumor necrosis factor stimulated nuclear translocation of p65-subunit of NF-kB. Overall data show that in vitro proteasome inhibition by WFA simultaneously promoted osteoblastogenesis by stabilizing RunX2 and suppressed osteoclast differentiation, by inhibiting osteoclastogenesis. Oral administration of WFA to osteopenic ovariectomized mice increased osteoprogenitor cells in the bone marrow and increased expression of osteogenic genes. WFA supplementation improved trabecular micro-architecture of the long bones, increased biomechanical strength parameters of the vertebra and femur, decreased bone turnover markers (osteocalcin and TNFα) and expression of skeletal osteoclastogenic genes. It also increased new bone formation and expression of osteogenic genes in the femur bone as compared with vehicle groups (Sham) and ovariectomy (OVx), Bortezomib (known PI), injectible parathyroid hormone and alendronate (FDA approved drugs). WFA promoted the process of cortical bone regeneration at drill-holes site in the femur mid-diaphysis region and cortical gap was bridged with woven bone within 11 days of both estrogen sufficient and deficient (ovariectomized, Ovx) mice. Together our data suggest that WFA stimulates bone formation by abrogating proteasomal machinery and provides knowledge base for its clinical evaluation as a bone anabolic agent.

Reaction of hypochlorous acid with imidazole: formation of 2-chloro- and 2-oxoimidazoles.

Reaction of hypochlorous acid (HOCl) with imidazole (Im) taken as a model for the 5-membered ring of guanine, leading to the products 2-chloro- and 2-oxo-imidazoles was investigated at the B3LYP/6-31+G* and B3LYP/AUG-cc-pVDZ levels of density functional theory. For all cases, single point energy calculations were performed at the MP2/AUG-cc-pVDZ level of theory using the geometries optimised at the B3LYP/AUG-cc-pVDZ level. Intrinsic reaction coordinate calculations were performed to ensure genuineness of all the calculated transition states. Effect of aqueous media was investigated by solvating all the species involved in the reactions using the polarizable continuum model. It is found that 2-chloroimidazole (2-ClIm) can be formed following three different reaction schemes while 2-oxoimidazole (2-oxoIm) can be formed following two different reaction schemes. The calculated barrier energies show that formation of 2-oxoIm would be less favored than that of 2-ClIm, which explains the experimental observations on relative yields of 8-chlorodeoxyguanosine and 8-oxodeoxyguanosine.

Electronic transitions of guanine tautomers, their stacked dimers, trimers and sodium complexes.

Planar and nonplanar geometries of the keto-N9H and keto-N7H tautomers of the guanine base of DNA as well as the hydrogen bonded complexes of these species with three water molecules each were optimized using the density functional theory at the B3LYP/6-31G** level. Geometries of the isolated bases were also optimized using the ab initio approach at the MP2/6-31G** level. The isolated keto-N9H and keto-N7H tautomers as well as their hydrogen bonded complexes with three water molecules each were solvated in bulk water employing the polarized continuum model (PCM) of the self-consistent reaction field theory (SCRF). Stacked dimers and trimers of both the tautomers of guanine were generated by placing the planar forms of the species at a fixed distance of 3.5 A from the neighboring one and rotating one molecule with respect to the other by 110 degrees for the keto-N9H form and 90 degrees for the keto-N7H form which corresponded to total energy minima at the B3LYP/6-31G** level. Geometry optimization for the cation of the monomer of guanine was performed at the same level of theory, and its solvation in bulk water was treated using the PCM model of the SCRF theory. The geometries of complexes of the two tautomers of guanine with a Na+ ion each were optimized at the B3LYP/6-31G** level, and the Na+ ion is predicted to bind with the keto-N9H tautomer preferentially. While the complex of the keto-N7H form of guanine with three water molecules in gas phase is slightly more stable than the corresponding complex of the keto-N9H form of guanine, the reverse is true in bulk water. Stacking interactions enhance the relative stability of the keto-N9H tautomer over that of the keto-N7H tautomer, suggesting that in bulk solutions, the former would be dominant. Electronic spectra of the isolated tautomers of guanine, those of their complexes with three water molecules each, the (keto-n9h and keto-n7h) cation of guanine, the complexes of the tautomers with a Na+ ion each, the stacked dimers and trimers of the two tautomers were calculated using configuration interaction involving single electron excitations (CIS). The relative absorption intensities of the two tautomers of guanine near 275 and 248 nm in the monomer, dimer, and trimer are predicated to be in the opposite order. Thus the absorption intensity oscillation observed using a guanine aqueous solution can be explained in terms of oscillation of relative populations of the two tautomers of the molecule. The 248 nm absorption peak would be appreciably red-shifted on formation of the cation of guanine. Binding of the Na+ ion with the two tautomers of guanine reduces intensities of their transitions appreciably and also it causes large red-shifts in the same.

A geometry optimization and molecular electrostatic potential mapping study of structure-activity relationship for some anti-Alzheimer agents.

Molecular geometries of some substituted (pyrroloamino)pyridines which possess anti-Alzheimer activity were optimized and potential-derived CHelpG point charges were computed using ab initio SCF molecular orbital approach employing the 3-21G basis set. AM1 molecular orbital calculations were performed using these optimized geometries and thus optimized Hybridization. Displacement Charges (HDC) combined with Löwdin charges continuously distributed in three dimension were obtained. Molecular electrostatic potential (MEP) maps of the molecules were obtained in two ways: (i) using the HDC-based model with the help of which MEP minima near the molecules were located, and (ii) using the CHelpG point charges, MEP values on the van der Waals surfaces of the molecules were computed. The MEP maps computed using both the methods have negative MEP regions near the pyridine nitrogen atom which appears to be the main binding site of the molecules with the appropriate receptor. Both electrostatic interaction and lipophilic association between these molecules and the receptor appear to contribute to biological activity.