Search

A 15-year-old Asian girl with severe atopic dermatitis was referred for dupilumab-associated blepharoconjunctivitis. Medical history was significant for severe atopic dermatitis. She was started on prednisolone acetate 1% ophthalmic suspension three times daily, and dupilumab injections were withheld after the initial visit. The patient was noted to have right lower eyelid ectropion, cicatricial occlusion, and severe punctal stenosis 6 weeks later. She was started on 0.03% tacrolimus ointment to the eyelid margin. Resolution of ectropion and restoration of punctal patency with residual stenosis were observed 4 weeks later. This is the first reported adolescent case of dupilumab-associated ectropion and punctal stenosis successfully treated with topical tacrolimus ointment. [ABSTRACT FROM AUTHOR]

Piperine is a pungent alkaloid, largely present in the skin of pepper. It is the most active component of pepper and being used as a medicine in many Asian countries. The effect of piperine on memory impairment and neurodegeneration in Alzheimer's disease model has been investigated. In the present study, we aim to investigate the effect of piperine molecule in different environments (crystal and active site of proteins) from crystallography, molecular docking, QM/MM based charge density analysis and molecular dynamic simulation. The crystal structure of piperine has been used to determine the topological electron density of intermolecular interactions. The O-atoms of piperine is forming C–H⋅⋅⋅O interactions with the neighboring molecules in the crystal, these interactions also confirmed from the Hirshfeld surface. Further, to understand the nature of interactions and the conformational flexibility of piperine in the active site of recombinant human acetylcholinesterase (rhAChE), molecular docking analysis has been performed. The selected docked complex suggests favorable hydrogen bonding and hydrophobic interactions with rhAChE enzyme; notably, the O3 atom of piperine molecule forms strong hydrogen bonding interaction with Glu202 at 1.8 Å. To determine the charge density distribution and the electrostatic properties of piperine molecule in the active site of rhAChE, the piperine-rhAChE complex was minimized at QM/MM energy level; in which, the binding pocket with piperine was considered as QM region. The charge density analysis of piperine and the interacting amino acid groups have been carried out. The topological analysis of O3⋯H–O/Glu202 hydrogen bonding interaction exhibits strong interactions and the electron density ρ cp (r) : 0.242 eÅ−3 and the Laplacian ∇ 2 ρ cp (r) : 3.176 eÅ−5 respectively. These results were compared with the corresponding molecule present in the crystal and gas phase environments of piperine. The comparison of active site structure with the corresponding crystal phase and gas phase structures reveal that piperine exhibits large conformational modification in the active site. The molecular dynamics simulation and binding free energy calculations were performed, this gives the stability, binding affinity of the molecule in the active site of rhAChE. The O3⋯H–O/Glu202 interaction shows the high stability (89.2%), this was confirmed from the stability of hydrogen bond analysis. The binding free energy was used to measure the rate of inhibition of enzyme in the presence of ligand molecule. The comparative study allows to understand the nature of piperine molecule in the gas and crystal phases, and amino acids environment. Image 1 • The nature of the intermolecular interactions and binding affinity between piperine and AChE enzyme determined using Crystallographic, QM/MM based charge density and MD analysis. • The QM/MM based charge density study is a complementary method of X-ray method for binding pocket analysis and it opens a new window to understand the strength of intermolecular interactions and binding affinity. • Due to intermolecular interactions, its conformation, charge density distribution and the electrostatic potentials are altered when the ligand present in the active site, this can be well understood on comparing with corresponding gas phase study. • The electronic level informations are much essential for drug design which can possible to explore this QM/MM based charge density analysis. [ABSTRACT FROM AUTHOR]

Abstract We developed customizable biomolecule functionalized 3D poly-ε-caprolactone (PCL) scaffolds reinforced with carbon nanofibers (CNF) for human meniscal tissue engineering. 3D nanocomposite scaffolds exhibited commendable mechanical integrity and electrical properties with augmented cytocompatibility. Especially, the functionalized 3D (10wt% CNF) scaffolds showed ~363% increase in compressive moduli compared to the pristine PCL. In dynamic mechanical analysis, these scaffolds achieved highest value (~42 MPa at 10 Hz) among all tested scaffolds including pristine PCL and human menisci (33, 41, 56 years). In vitro results were well supported by the outcomes of cell proliferation analysis, microscopic images, Hoechst staining and extracellular-matrix estimation. Further, in vivo rabbit bio toxicity studies revealed scaffold's non-toxicity and its future potential as a meniscus scaffold. This study also indicates that the incorporation of CNF in polymer matrix may be optimized based on mechanical properties of patient meniscus and it may help in developing the customized patient specific 3D constructs with improved multifunctional properties. Graphical Abstract We developed customizable biomolecule functionalized 3D poly caprolactone (PCL) scaffolds reinforced with carbon nanofibers (CNF) for human meniscal tissue engineering. Highly porous, electrically conductive 3D nanocomposite scaffolds exhibited porous nanoarchitectures which facilitated enhanced mechanical integrity and meniscus cell augmentation in vitro. In vivo biocompatibility studies on rabbits show admirable results. Unlabelled Image Highlights • Biomolecules incorporated 3D PCL/CNF nanocomposite scaffolds have been developed for meniscal tissue engineering. • Nanoporous honeycomb garland like structures are created on the pore walls of these scaffolds which enhanced total surface area and porosity without compromising mechanical property. • When compared to human meniscus samples and control scaffold, these nanocomposite scaffolds exhibit better static and dynamic mechanical properties. • Meniscal cells are found to get attached to the honeycomb garland structured pore walls and proliferate to cover entire scaffold. • Scaffolds were subcutaneously implanted in New Zealand white rabbits. • Biochemical and immunohistochemistry analysis showed their in vivo biocompatibility which confirms suitability and potential of scaffolds as meniscal substitute. [ABSTRACT FROM AUTHOR]

Due to Corona Virus disease -19, India saw a surge of mucormycosis cases, associated with high death rate. India, during the month of May to July 2021 saw a surge of mucormycosis from all states, with close to 50,000 cases just in a span of 3 months. To examine the histopathological appearances of rhino-orbital/rhino-maxillary/sino-nasal mucormycosis in the backdrop of the ongoing COVID 19 pandemic. The study involved analysis of 60 biopsy samples of suspected rhino-maxillary /rhino-orbital mucormycosis received from post-COVID-19 patients. A preliminary review of the slides showing hyphal forms of fungal organisms with un-doubtful tissue / mucosal invasion was included. All samples were examined under Hematoxylin and Eosin stains along with special fungal stains. Data thus obtained were analyzed statistically. Special stains for fungus namely Periodic Acidic Schiff (PAS) and Gomori Methenamine silver (GMS) were utilized to confirm and/or to differentiate the fungal organisms and to highlight the cell wall of the fungus. The mean age of the patients with mucormycosis was 51.68 years and 72 (83.33%) of them were males. Acute type of inflammation was noted in 44 (73.33%), granulomatous inflammation in 14 (23.33%) of cases. Bony invasion and perineural invasion was observed in 5 (8.33%) and 55 (91.67%) cases, respectively. The dominant fungus were mucorales in 58 (96.67%), aspergillous, along with mucorales in 12 (20%) and combination of mucorales and candida identified in 8 (13.33%) cases. Besides all the histological appearance of angioinvasion, bone, and soft tissue invasion, a notable aspect was the shift in inflammatory pattern, which was more granulomatous in nature, with a decrease in fungal load correlating with the drop of COVID second wave. This proves that as immunity develops, the host's response to secondary opportunistic infections changes. [ABSTRACT FROM AUTHOR]

Summary: GTPases of immunity-associated proteins (GIMAPs) are regulators of lymphocyte survival and homeostasis. We previously determined the structural basis of GTP-dependent GIMAP2 scaffold formation on lipid droplets. To understand how its GTP hydrolysis is activated, we screened for other GIMAPs on lipid droplets and identified GIMAP7. In contrast to GIMAP2, GIMAP7 displayed dimerization-stimulated GTP hydrolysis. The crystal structure of GTP-bound GIMAP7 showed a homodimer that assembled via the G domains, with the helical extensions protruding in opposite directions. We identified a catalytic arginine that is supplied to the opposing monomer to stimulate GTP hydrolysis. GIMAP7 also stimulated GTP hydrolysis by GIMAP2 via an analogous mechanism. Finally, we found GIMAP2 and GIMAP7 expression differentially regulated in several human T cell lymphoma lines. Our findings suggest that GTPase activity in the GIMAP family is controlled by homo- and heterodimerization. This may have implications for the differential roles of some GIMAPs in lymphocyte survival. [ABSTRACT FROM AUTHOR]

Abstract: The present study aims to estimate and validate the glycated haemoglobin (HbA1c) using non-contact infrared thermography. The diagnostic threshold was set as (HbA1c ⩾48mmol/mol). The optimal regression model [r =0.643, p =0.000] was achieved from the significant variables correlating with the HbA1c and the validation was performed against the bio-chemical assay to indicate the sensitivity, specificity, positive predictive value, negative predictive value and with an accuracy of [90%, 55%, 65%, 85% and 72%] respectively. The non-invasive core body temperature measurement at the inner canthi of eye [r =−0.462, p <0.01] indicated negative correlation with HbA1c, that signifies the early metabolic changes. In type 2 diabetes, the core body temperature decreases with a decrease in the body metabolism. Thereby, a truly non-invasive infrared thermography could be used for obtaining the accurate HbA1c with no blood sample extraction; further, it could be used as the preferred diagnostic tool for type 2 diabetes. [Copyright &y& Elsevier]

Abstract: Focused ion beam (FIB) milling is the micro and nano scale manufacturing process, in which components are fabricated with the micro and nano scale resolution. Micro surgical instruments, micro machining tools, probes of scanning probe microscopy and various other small sized components are fabricated using FIB milling. Due to the favorable properties like hardness and wear resistance, high speed steel (HSS) is one of the choices to fabricate many small scale components. While fabricating small scale components, a part of removed material redeposit onto the machined surface, which is known as redeposition. One of the effects of redeposition is that it impairs dimensional accuracy of work material. HSS work material is investigated for the effect of redeposition during FIB milling and existing mathematical model of depth of sputtering has been modified to take into account the effect of redeposition. The ratio of rate of redeposition to the beam velocity has been evaluated for different beam velocities to validate the modified mathematical model of depth of sputtering and more accurate results of depth of sputtering are achieved with the modified model. [Copyright &y& Elsevier]

Abstract: Traumatic brain injury (TBI) constitutes a major global health and socio-economic problem with neurobehavioral sequelae contributing to long-term disability. It causes brain swelling, axonal injury and hypoxia, disrupts blood brain barrier function and increases inflammatory responses, oxidative stress, neurodegeneration and leads to cognitive impairment. Epidemiological studies show that 30% of patients, who die of TBI, have Aβ plaques which are pathological features of Alzheimer''s disease (AD). Thus TBI acts as an important epigenetic risk factor for AD. This review focuses on AD related genes which are expressed during TBI and its relevance to progression of the disease. Such understanding will help to diagnose the risk of TBI patients to develop AD and design therapeutic interventions. [Copyright &y& Elsevier]

Abstract: Trichomonas vaginalis, a flagellate protozoan parasite commonly found in the human genitourinary tract, is transmitted primarily by sexual intercourse. Diagnosis is usually by in vitro culture method and staining with Giemsa stain. There are laboratories that use Gram stain as well. We compared the use of modified Field''s (MF), Giemsa, and Gram stains on 2 axenic and xenic isolates of T. vaginalis, respectively. Three smears from every sediment of spun cultures of all 4 isolates were stained, respectively, with each of the stains. We showed that MF staining, apart from being a rapid stain (20 s), confers sharper staining contrast, which differentiates the nucleus and the cytoplasm of the organism when compared to Giemsa and Gram staining especially on parasites from spiked urine samples. The alternative staining procedure offers in a diagnostic setting a rapid stain that can easily visualize the parasite with sharp contrasting characteristics between organelles especially the nucleus and cytoplasm. Vacuoles are more clearly visible in parasites stained with MF than when stained with Giemsa. [Copyright &y& Elsevier]

Dissipation study of sulfosulfuron in natural water and its bioaccumulation in fish was conducted at 25±2°C and at two different concentration levels 1mgl−1 and 2mgl−1. The dissipation data in water showed the DT50 and DT90 values 67–76 and 222–253 days and followed first order kinetics. Bioaccumulation of sulfosulfuron in fish was conducted under static conditions exposing the fish at one-tenth of sub-lethal concentration 9mgl−1 and at double the concentration 18mgl−1, for a period of 56 days. On different occasions fish samples were collected and analyzed. A HPLC-RF method was used for the quantification of sulfosulfuron and aminopyrimidine with the limit of quantification 0. 001μgml−1. Results showed the accumulation of residues of sulfosulfuron in fish over the concentration range 0. 009–0. 496μgg−1. Both in water and fish samples, identified the presence of metabolites aminopyrimidine, desmethyl sulfosulfuron, guanidine, sulfonamide, ethyl sulfone and rearranged amine. The formations of these metabolites are confirmed by LC-MS/MS analysis. An LC-MS/MS electro spray ionization technique was used for this purpose. One of the metabolite Aminopyrimidine was identified at higher concentration levels (0. 01–0. 1μgml−1) when compared with other metabolites. Subsequently dissipation of aminopyrimidine in water and its bioaccumulation was also studied at the concentration level 1mgl−1 and 2mgl−1. The calculated DT50 and DT90 values are 66–68 days and 218–226 days, respectively. This followed first order kinetics. Three hundred days after the exposure complete demineralization was observed. [Copyright &y& Elsevier]

Abstract: This paper proposes fuzzy system and neural network approaches to identify the incipient faults in the power transformer using dissolved gas analysis (DGA) method. Using the IEC/IEEE DGA criteria and the gas concentration values as references the fuzzy diagnosis system and neural network are built. The proposed systems are verified using practical data collected from Electricity Board. The fuzzy system is tested with triangular, trapezoidal and Gaussian membership functions and its effectiveness is analyzed through simulation in terms of accuracy in identifying the transformer faults. The proposed Back propagation network is verified to overcome the drawbacks of conventional methods. The proposed schemes are simulated and tested in the software environment. The simulation results are presented. [Copyright &y& Elsevier]

This study evaluated the influence of adiposity on the progression of left ventricular (LV) mass from childhood to adulthood and the relation of LV mass to insulin resistance in young adulthood. One hundred thirty-two healthy children recruited into a longitudinal study at a mean age of 13 years and reevaluated at 27 years, at which time insulin resistance studies were also performed, were studied. Echocardiographic assessment of LV mass was made and indexed for height2.7. Body mass index (BMI) at 13 years was highly correlated with BMI at 27 years, as was LV mass index at 13 and 27 years. The cross-sectional correlation of LV mass index and BMI at 13 years (r = 0.38, p <0.0001) had strengthened considerably by 27 years (r = 0.55, p <0.0001). A BMI increase ≥5.5 kg/m2 from 13 to 27 years was associated with a significantly greater increase in the LV mass index (p <0.0001) than a BMI change <5.5 kg/m2, and this relation was similar in children who were thin and heavy at baseline. In young adulthood, the relation of LV mass index to lean mass was weaker than that of LV mass index to fat mass. The association of LV mass with insulin resistance was dependent on adiposity. In conclusion, adiposity and LV mass are related in childhood, and this association tracks and becomes stronger in young adulthood. Moreover, the increase in LV mass from childhood to young adulthood is related to the degree of increase in BMI, independent of BMI at 13 years, suggesting that an excessive increase in LV mass could be limited by controlling gain in body fat during adolescence. [Copyright &y& Elsevier]

Traumatic brain injury is a highly irreversible process that consists of primary as well as secondary injury which develops and progresses over months to years, leading to cognitive dysfunctions. Vitamin B 12 received considerable interest due to its potential therapeutic properties. The pathways of vitamin B 12 are closely related to neuronal survival but its effects on the pathophysiology of injury with respect to cognition is a relatively unexplored area of research. In this study, we investigated, the effect of vitamin B 12 and its involvement in neuroprotection on TBI-induced pathophysiology in male Swiss albino mice. Our findings suggested that vitamin B 12 supplementation improves TBI-mediated neurological impairments, spatial and recognition memory, and anxiety-like behavior. Furthermore, the oxidative stress was reduced by declined homocysteine level with vitamin B 12 supplementation validating declined expression of astrocytes and TBI biomarkers. The studies on neuronal morphology revealed that vitamin B 12 supplementation increases the dendritic arborization and density of mushroom and filopodia-shaped spines and further increases the expression of synaptic plasticity-related genes and proteins. Taken together, our findings reveal that, supplementation of vitamin B 12 restored the TBI-induced downregulation of dendritic arborization, and spine density which ultimately increases synaptic plasticity, cell survival, and recovery of cognitive dysfunctions. [Display omitted] • Vitamin B 12 improves cognitive dysfunction after traumatic brain injury (TBI). • It also reduces the homocysteine and oxidative stress after TBI. • Similarly, it improves dendritic arborization and spine density after TBI. • It also, decreases neurodegeneration after TBI. [ABSTRACT FROM AUTHOR]

Cognitive abilities are compromised with advancing age posing a great risk for the development of dementia and other related brain disorders. Genetic susceptibility as well as environmental exposures determine the fate of cognitive aging and its transition to pathological states. Emerging epidemiological and observational studies have revealed the importance of lifestyle factors including dietary patterns and nutritional intake in the maintenance of cognitive health and reducing the risk of neurodegenerative disorders. In this context, nutraceutical interventions have gained considerable attention in preventing age-related cognitive deficits and counteracting pathological processes. Nutraceuticals include dietary plants and derivatives, food supplements and processed foods with nutritional and pharmaceutical values. The present review highlights the importance of nutraceuticals in attenuating cognitive aging and its progression to dementia, with specific emphasis on chemical constituents, neurocognitive properties and mechanism of action. • Nutritional imbalance is a key risk factor for cognitive aging and disorders. • Nutraceutical intervention delays cognitive aging and its progression to dementia. • Nutraceuticals have antioxidant, anti-inflammatory and neuromodulatory properties. [ABSTRACT FROM AUTHOR]

The grinding of Si 3 N 4 ceramics is difficult due to their inherent hardness, brittleness, and machining-induced damages. The effects of environmentally friendly mono and hybrid nanofluids are investigated on grinding forces, specific grinding energy, grinding force ratio, surface integrity and surface/sub-surface damages during grinding of Si 3 N 4 ceramics. The experimental results indicated superior lubrication properties of MoS 2 nanoparticles based nanofluids. The reduction in normal grinding force and specific grinding energy for MoS 2 – WS 2 hybrid nanofluids has been 27% and 39% respectively, compared to deionized water base fluid. The surface roughness and chipping layer depth of silicon nitride workpieces using MoS 2 – WS 2 hybrid nanofluid have been reduced by 41% and 86% in comparison to flood grinding. The thermally stable oxides on ground surface attributed to grindabilty improvement. [ABSTRACT FROM AUTHOR]

Abstract Tool surface modification strategies are expected to achieve energy efficient dry cutting pertaining tribological advantages of textured surfaces. Current work focuses on both experimental and finite element based approaches to understand the effect of textured and coated textured tools on machining performance of Ti6Al4V alloy. Novel chevron textured tools were fabricated using nanosecond fiber laser and further coated with PVD-TiAlN coating. 2D FE simulation studies for turning with uncoated textured and TiAlN coated-textured tools were performed and compared with plain and coated-plain tools. The effectiveness of the textured tools is evaluated in terms of cutting forces, average friction coefficient, tool-chip contact length, chip disentangling behavior, and shear stresses between coating-substrate adhesions. Results confirm that the coated textured tool is helpful in machining performance improvement of Ti6Al4V alloys even at comparatively higher cutting speeds and feed. The concept of interface multipoint micro-cutting (IMP-μC) at varying machining speeds was observed from FE simulations and verified from experimental results. Highlights • Plain and chevron textured tools were used with uncoated and TiAlN coatings for turning of Ti6Al4V. • Cutting tests were conducted for forces, apparent friction, chip contact length, curling and disentangling behavior. • Experimental results are validated for FE simulations and compared for the analysis. • Texture induced derivative cutting phenomenon is explained with FE simulations and experimentally validated. • Reduction in maximum shear stresses at flank for textured tools reduced delamination of coatings. [ABSTRACT FROM AUTHOR]

An efficient method of lubrication and cooling for green machining is nanofluid minimum quantity lubrication (NMQL). Compared to other vegetable-based oils, coconut oil has the highest viscosity index, lubricity, and oxidative characteristics, making it a popular trending lubricant for decreasing friction. However, its performance at higher temperatures degrades owing to higher saponification value. In order to improve its performance, the solid nano-friction modifier (hBN) is dispersed in it, and the colloid is called a nanofluid. UV–Vis–NIR spectrophotometer, HR-TEM, and FTIR spectroscopy characterize nanofluid. The stability of nanofluid at 0.3 vol% of hBN has been observed to be the highest compared to other volume fractions. Compared to coconut oil, prepared nanofluid is superior in terms of increased thermal conductivity, thermal stability, and viscosity for all the tested temperature ranges. Nanofluid shows increased viscosity index (VI) by 20%, reduced contact angle by 45%, and lower coefficient of friction (COF) by 32% compared to coconut oil. Further performance of this modified biodegradable nanofluid under Minimum quantity lubrication (MQL) on end milling of Incoloy 925 has been studied. In order to compare the machining performance under different cutting environments, cutting temperature, cutting force, specific cutting energy, power consumption, carbon emission, chip morphology, surface topology/topography, and tool wear were evaluated. Finally, sustainability assessments for different cutting environments have been performed. Biodegradable oil-based NMQL-assisted machining has performed better than dry and MQL-assisted machining. [Display omitted] [ABSTRACT FROM AUTHOR]

Effect of texture shapes and texture area density for machining applications is a potential topic of investigation. However, it is difficult to fabricate perfect dimensions by using available micromachining techniques. Finite element simulations can be an effective way to understand the effect of texture density, texture depth and different geometric shapes on machining performances. The present study deals with the 3D finite element investigations of different texture shapes to predict cutting forces during machining of titanium alloy under dry condition. Available Johnson–Cook material model parameters have been investigated to select suitable parameters for 3D finite element studies in titanium machining. Different geometrical shapes (circular, square, triangular and elliptical shape) with the constant area are modeled at the rake face of cutting tools to incorporate textures. The effects of texture shape are studied for variation in cutting forces with different texture area density and depth. The effect of texture shape is found to be less influential for dry cutting however area density is found to have the most dominant effect on cutting forces. Further, the linear regression model for tool–chip contact length has been developed for the textured and untextured tools under different machining parameters. The developed model has incorporated the chip serration effect (serration peak and valley heights) in the contact length model. The contact length model for the textured tool has been developed for the first time, and the contact length variation has been compared with the plain tools. The results reveal that textured tools have limited applicability for dry cutting of titanium alloys. Further, the associated mechanism of contact area reduction for textured tools has been found to be not applicable at increased feed and cutting speeds due to chip embedment into textured space. [ABSTRACT FROM AUTHOR]