Search

Carbohydrate-functionalized gold nanoparticles were employed to differentiate plant-legume lectins using a statistical analysis method of linear discriminant analysis (LDA). Various carbohydrates were conjugated on gold nanoparticles, and the resulting glyconanoparticles were treated with lectins. Changes in the localized surface plasmon resonance of the glyconanoparticles upon lectin binding were recorded, and the data were subjected to LDA. Results showed that the glyconanoparticles successfully differentiated all lectins. [ABSTRACT FROM AUTHOR]

Fibrosing interstitial lung diseases (ILDs) encompass a diverse range of scarring disorders that lead to progressive lung failure. Previous gene expression profiling studies focused on idiopathic pulmonary fibrosis (IPF) and bulk tissue samples. We employed digital spatial profiling to gain new insights into the spatial resolution of gene expression across distinct lung microenvironments (LMEs) in IPF, chronic hypersensitivity pneumonitis (CHP) and non-specific interstitial pneumonia (NSIP). We identified differentially expressed genes between LMEs within each condition, and across histologically similar regions between conditions. Uninvolved regions in IPF and CHP were distinct from normal controls, and displayed potential therapeutic targets. Hallmark LMEs of each condition retained distinct gene signatures, but these could not be reproduced in matched lung tissue samples. Based on these profiles and unsupervised clustering, we grouped previously unclassified ILD cases into NSIP or CHP. Overall, our work uniquely dissects gene expression profiles between LMEs within and across different types of fibrosing ILDs., (© 2024. The Author(s).)

Aim: Chronic stroke walking impairment is associated with high healthcare resource utilization (HCRU) costs. InTandem™ is a neurorehabilitation system that autonomously delivers a rhythmic auditory stimulation (RAS)-based intervention for the at-home rehabilitation of walking impairment in adults in the chronic phase of stroke recovery. This study was conducted to estimate the budget impact of InTandem in comparison with currently available intervention strategies for improvement of gait/ambulation in individuals with chronic stroke walking impairment. Methods & materials: A budget impact analysis (BIA) for InTandem was conducted based on a 1-million-member US third-party payer perspective over a 1-year time horizon. Key inputs for the budget impact model were: costs for each intervention strategy (InTandem, physical therapy, self-directed walking and no treatment), HCRU costs for persons with chronic stroke and anticipated HCRU cost offsets due to improvements in gait/ambulatory status as measured by self-selected comfortable walking speed (based on functional ability). In addition to the reference case analysis, a sensitivity analysis was conducted. Results: Based on the reference case, introduction of InTandem was projected to result in overall cost savings of $439,954 in one year. Reduction of HCRU costs (-$2,411,778) resulting from improved walking speeds with InTandem offset an increase in intervention costs (+$1,971,824). Demonstrations of cost savings associated with InTandem were robust and were consistently evident in nearly all scenarios evaluated in the sensitivity analysis (e.g., with increased/decreased patient shares, increased HCRU cost or increased InTandem rental duration). Conclusion: The InTandem system is demonstrated to improve walking and ambulation in adults in the chronic phase of stroke recovery after a five-week intervention period. The BIA predicts that introduction of InTandem will be associated with overall cost savings to the payer.

Background: Seroprevalence studies have shown that 70% of children are exposed to Cryptococcus , the most common cause of meningitis in people living with human immunodeficiency virus (HIV), but reported pediatric disease prevalence is much lower than in adults., Methods: PubMed and Ovid Global Health databases were searched with the terms "cryptococcosis," "cryptococcal meningitis," " Cryptococcus neoformans " or " Cryptococcus gattii ." All studies reporting pediatric specific data in the English language from 1980 up until December 2022 were included., Results: One hundred sixty-eight publications were reviewed totaling 1469 children, with the majority reported from Africa (54.2%). Sixty-five percent (961) were HIV positive, 10% (147) were non-HIV immunocompromised and 19% (281) were immunocompetent. Clinical signs and symptoms were only reported for 458 children, with fever (64%), headache (55%) and vomiting (39%) being the most common. Most children (80%) suffered from meningoencephalitis. Lung involvement was rarely described in HIV-positive children (1%), but significantly more common in the non-HIV immunocompromised (36%) and immunocompetent (40%) groups ( P < 0.0001). Only 22% received the recommended antifungal combination therapy, which was significantly higher in immunocompetent children than those with HIV (39% vs. 6.8%; P < 0.0001). Overall mortality was 23%. A significant higher mortality was observed in children with HIV compared with immunocompetent children (32% vs. 16%; P < 0.001), but not compared with children with non-HIV immunosuppression (25)., Conclusions: This is the largest review of pediatric cryptococcosis with new observations on differences in clinical presentation and outcome depending on the underlying condition. The lack of granular clinical data urges prospective clinical epidemiological studies for improved insight in the epidemiology, management and outcome of cryptococcosis in children., Competing Interests: A.W. has received consultant fees from Gilead and Mundipharma and payment for educational events from Gilead and F2G. The other authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This paper aims to identify the revised international marketing strategies in communication during the COVID-19 pandemic by utilizing the firm's resources and capabilities. We conducted in-depth interviews and a questionnaire survey with key stakeholders of retail organizations which changed their digital marketing strategies during COVID-19. The data is collected from 587 respondents from different parts of the world through resource orchestration theory. The qualitative findings support a high degree of association among the firm's resources and capabilities, leveraging processes based on the revised international marketing strategies during the COVID-19 pandemic. We have developed a conceptual model based on these findings with six variables: leveraging process of the firm's capabilities information technology-related resources; information technology-related capabilities, dynamic capabilities, environmental uncertainty, and leveraging process of the firm's resources. However, environmental uncertainty and leveraging of the firm's resources were not influential in forming digital marketing strategies during COVID-19. This study proposes a new process for international marketing managers in business organizations to restructure the resources within their organizations by creating new capabilities and leveraging them., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Elsevier Inc. All rights reserved.)

Seneca Valley virus (SVV) is a newly discovered picornavirus in the Senecavirus genus. SVV-001 strain has shown promise as an oncolytic virus against tumors with neuroendocrine features. There is a need to use a structure-based approach to develop virus-like particles capable to mimicking the architecture of naturally occurring empty capsids that can be used as vaccines or as carriers for targeted cancer treatment. However, these empty capsids are inherently less stable, and tedious to purify. This warrants investigation into factors which confer the SVV capsid stability and into combining this knowledge to recombinantly express stable SVV VLPs. In this study, we isolated a thermostable mutant of SVV by thermal selection assays and we characterized a single mutation located in a capsid protein. The cryo-EM map of this mutant showed conformational shifts that facilitated the formation of additional hydrogen bonds and aromatic interactions, which could serve as capsid stabilizing factors., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Idiopathic pulmonary fibrosis (IPF) is associated with increased expression of cyclin-dependent kinase inhibitors such as p16 and p21, and subsequent induction of cell cycle arrest, cellular senescence, and pro-fibrotic gene expression. We sought to link p16-expression with a diagnosis of IPF or other fibrotic interstitial lung diseases (ILDs), radiographic pattern, senescent foci-specific gene expression, antifibrotic therapy response, and lung transplant (LTx)-free survival., Methods: Eighty-six cases of fibrosing ILD were identified with surgical lung biopsy. Immunohistochemistry for p16 was performed on sections with the most active fibrosis. p16-positive foci (loose collection of p16-positive fibroblasts with overlying p16-positive epithelium) were identified on digital slides and quantified. Cases were scored as p16-low (≤ 2.1 foci per 100 mm 2 ) or p16-high (> 2.1 foci per 100 mm 2 ). Twenty-four areas including senescent foci, fibrotic and normal areas were characterized using in situ RNA expression analysis with digital spatial profiling (DSP) in selected cases., Results: The presence of p16-positive foci was specific for the diagnosis of IPF, where 50% of cases expressed any level of p16 and 26% were p16-high. There was no relationship between radiographic pattern and p16 expression. However, there was increased expression of cyclin-dependent kinase inhibitors, collagens and matrix remodeling genes within p16-positive foci, and cases with high p16 expression had shorter LTx-free survival. On the other hand, antifibrotic therapy was significantly protective. DSP demonstrated that fibroblastic foci exhibit transcriptional features clearly distinct from that of normal-looking and even fibrotic areas., Conclusions: We demonstrated the potential clinical applicability of a standardized quantification of p16-positive fibroblastic foci. This method identifies an IPF phenotype associated with foci-specific upregulation of senescence-associated and matrix remodeling gene expression. While these patients have reduced LTx-free survival, good response to antifibrotic therapies was observed in those who were treated., (© 2022. The Author(s).)

Enteroviruses (EVs) represent a substantial concern to global health. Here, we present the cryo-EM structure of a non-human enterovirus, EV-F4, isolated from the Australian brushtail possum to assess the structural diversity of these picornaviruses. The capsid structure, determined to ~3 Å resolution by single particle analysis, exhibits a largely smooth surface, similar to EV-F3 (formerly BEV-2). Although the cellular receptor is not known, the absence of charged residues on the outer surface of the canyon suggest a different receptor type than for EV-F3. Density for the pocket factor is clear, with the entrance to the pocket being smaller than for other enteroviruses.

Seneca Valley virus (SVV) is a picornavirus with potency in selectively infecting and lysing cancerous cells. The cellular receptor for SVV mediating the selective tropism for tumors is anthrax toxin receptor 1 (ANTXR1), a type I transmembrane protein expressed in tumors. Similar to other mammalian receptors, ANTXR1 has been shown to harbor N-linked glycosylation sites in its extracellular vWA domain. However, the exact role of ANTXR1 glycosylation on SVV attachment and cellular entry was unknown. Here we show that N-linked glycosylation in the ANTXR1 vWA domain is necessary for SVV attachment and entry. In our study, tandem mass spectrometry analysis of recombinant ANTXR1-Fc revealed the presence of complex glycans at N166, N184 in the vWA domain, and N81 in the Fc domain. Symmetry-expanded cryo-EM reconstruction of SVV-ANTXR1-Fc further validated the presence of N166 and N184 in the vWA domain. Cell blocking, co-immunoprecipitation, and plaque formation assays confirmed that deglycosylation of ANTXR1 prevents SVV attachment and subsequent entry. Overall, our results identified N-glycosylation in ANTXR1 as a necessary post-translational modification for establishing stable interactions with SVV. We anticipate our findings will aid in selecting patients for future cancer therapeutics, where screening for both ANTXR1 and its glycosylation could lead to an improved outcome from SVV therapy.

Background: Melioidosis is considered endemic in certain areas of the world. Musculoskeletal and soft tissue involvement are relatively uncommon presentations in melioidosis. We present a case of infective myositis in a patient with melioidosis in Sri Lanka, which is not considered an endemic country. Even though multiple cases of melioidosis have been reported with an increasing number in Sri Lanka, infective myositis secondary to melioidosis was not reported previously., Case Presentation: A 60-year-old Sinhalese man with diabetes presented with fever of 4 months' duration and a limp with a painful lump on the right side of the upper thigh of 2 months' duration. He had been treated in a local hospital for community-acquired pneumonia 3 weeks prior to this admission, for which he had received intravenous meropenem and teicoplanin with intensive care unit admission. He had a 0.5-cm × 0.5-cm tender lump over the right vastus lateralis muscle, and contrast-enhanced computed tomography of the area showed an ill-defined, heterogeneously enhancing, hypodense area involving the vastus lateralis, vastus intermedius, and quadratus femoris, suggestive of infective myositis but without abscess formation. Histopathology of the muscle biopsied from the vastus lateralis showed suppurative inflammation of subcutaneous fat with connective tissue necrosis and muscle infiltrated by lymphocytes. These features are suggestive of infective myositis possibly due to melioidosis. Although the result of a culture taken from the muscle biopsy was negative, the patient's antibody titer was strongly positive for melioidosis. He did not show any other areas with infected foci. He was treated with intravenous meropenem for 2 weeks and responded well. He was discharged with trimethoprim-sulfamethoxazole for 6 months as a maintenance therapy., Conclusion: Melioidosis is commonly an undiagnosed disease that has a wide variety of clinical presentations. Myositis in melioidosis is uncommon, and careful evaluation is mandatory to avoid misdiagnosis of this treatable but fatal disease. The clinician should have a high index of clinical suspicion, and further clinical and epidemiological studies are needed to determine the true burden of the disease.

Oncolytic viruses (OVs) form a group of novel anticancer therapeutic agents which selectively infect and lyse cancer cells. Members of several viral families, including Picornaviridae , have been shown to have anticancer activity. Picornaviruses are small icosahedral non-enveloped, positive-sense, single-stranded RNA viruses infecting a wide range of hosts. They possess several advantages for development for cancer therapy: Their genomes do not integrate into host chromosomes, do not encode oncogenes, and are easily manipulated as cDNA. This review focuses on the picornaviruses investigated for anticancer potential and the mechanisms that underpin this specificity., Competing Interests: The authors declare no conflict of interest.

Recently, the use of oncolytic viruses in cancer therapy has become a realistic therapeutic option. Seneca Valley Virus (SVV) is a newly discovered picornavirus, which has earned a significant reputation as a potent oncolytic agent. Anthrax toxin receptor 1 (ANTXR1), one of the cellular receptors for the protective antigen secreted by Bacillus anthracis , has been identified as the high-affinity cellular receptor for SVV. Here, we report the structure of the SVV-ANTXR1 complex determined by single-particle cryo-electron microscopy analysis at near-atomic resolution. This is an example of a shared receptor structure between a mammalian virus and a bacterial toxin. Our structure shows that ANTXR1 decorates the outer surface of the SVV capsid and interacts with the surface-exposed BC loop and loop II of VP1, "the puff" of VP2 and "the knob" of VP3. Comparison of the receptor-bound capsid structure with the native capsid structure reveals that receptor binding induces minor conformational changes in SVV capsid structure, suggesting the role of ANTXR1 as an attachment receptor. Furthermore, our results demonstrate that the capsid footprint on the receptor is not conserved in anthrax toxin receptor 2 (ANTXR2), thereby providing a molecular mechanism for explaining the exquisite selectivity of SVV for ANTXR1., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Sepsis-associated encephalopathy manifesting as delirium is a common problem in critical care medicine. In this study, patients that had delirium due to sepsis had significant cognitive impairments at 12-18 months after hospital discharge when compared with controls and Cambridge Neuropsychological Automated Test Battery-standardized scores in spatial recognition memory, pattern recognition memory, and delayed-matching-to-sample tests but not other cognitive functions. A mouse model of S. pneumoniae pneumonia-induced sepsis, which modeled numerous aspects of the human sepsis-associated multiorgan dysfunction, including encephalopathy, also revealed similar deficits in spatial memory but not new task learning. Both humans and mice had large increases in chemokines for myeloid cell recruitment. Intravital imaging of the brains of septic mice revealed increased neutrophil and CCR2+ inflammatory monocyte recruitment (the latter being far more robust), accompanied by subtle microglial activation. Prevention of CCR2+ inflammatory monocyte recruitment, but not neutrophil recruitment, reduced microglial activation and other signs of neuroinflammation and prevented all signs of cognitive impairment after infection. Therefore, therapeutically targeting CCR2+ inflammatory monocytes at the time of sepsis may provide a novel neuroprotective clinical intervention to prevent the development of persistent cognitive impairments.

Seneca Valley virus (SVV), like some other members of the Picornaviridae , forms naturally occurring empty capsids, known as procapsids. Procapsids have the same antigenicity as full virions, so they present an interesting possibility for the formation of stable virus-like particles. Interestingly, although SVV is a livestock pathogen, it has also been found to preferentially infect tumor cells and is being explored for use as a therapeutic agent in the treatment of small-cell lung cancers. Here we used cryo-electron microscopy to investigate the procapsid structure and describe the transition of capsid protein VP0 to the cleaved forms of VP4 and VP2. We show that the SVV receptor binds the procapsid, as evidence of its native antigenicity. In comparing the procapsid structure to that of the full virion, we also show that a cage of RNA serves to stabilize the inside surface of the virus, thereby making it more acid stable. IMPORTANCE Viruses are extensively studied to help us understand infection and disease. One of the by-products of some virus infections are the naturally occurring empty virus capsids (containing no genome), termed procapsids, whose function remains unclear. Here we investigate the structure and formation of the procapsids of Seneca Valley virus, to better understand how they form, what causes them to form, how they behave, and how we can make use of them. One potential benefit of this work is the modification of the procapsid to develop it for targeted in vivo delivery of therapeutics or to make a stable vaccine against SVV, which could be of great interest to the agricultural industry., (Copyright © 2018 American Society for Microbiology.)

Amyloid fibrils are a class of insoluble protein nanofibers that are formed via the self-assembly of a wide range of peptides and proteins. They are increasingly exploited for a broad range of applications in bionanotechnology, such as biosensing and drug delivery, as nanowires, hydrogels, and thin films. Amyloid fibrils have been prepared from many proteins, but there has been no definitive characterization of amyloid fibrils from hemoglobin to date. Here, nanofiber formation was carried out under denaturing conditions using solutions of apo-hemoglobin extracted from bovine waste blood. A characteristic amyloid fibril morphology was confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM), with mean fibril dimensions of approximately 5 nm diameter and up to several microns in length. The thioflavin T assay confirmed the presence of β-sheet structures in apo-hemoglobin fibrils, and X-ray fiber diffraction showed the characteristic amyloid cross-β quaternary structure. Apo-hemoglobin nanofibers demonstrated high stability over a range of temperatures (-20 to 80 °C) and pHs (2-10), and were stable in the presence of organic solvents and trypsin, confirming their potential as nanomaterials with versatile applications. This study conclusively demonstrates the formation of amyloid fibrils from hemoglobin for the first time, and also introduces a cost-effective method for amyloid fibril manufacture using meat industry by-products.

Ten herbal teas (Acacia arabica, Aegle marmelos flower, A. marmelos root bark, Aerva lanata, Asteracantha longifolia, Cassia auriculata, Hemidesmus indicus, Hordeum vulgare, Phyllanthus emblica, Tinospora cordifolia) were fermented with the Kombucha 'tea fungus'. The pH values of the fermented beverages ranged from 4.0 to 6.0 by day 7, while the titratable acidity ranged from 2.5 to 5.0g/mL (P<0.05). Gallic acid had statistically significantly increased (P<0.05) in almost all the samples by day 7. The Oxygen radical absorbance capacity assay indicated 5 of the Kombucha beverages to have statistically significant increases (P<0.05) by day 7. The α-amylase inhibitory activities ranged from 52.5 to 67.2μg/mL in terms of IC50 values following fermentation, while the α-glucosidase inhibitory activities ranged from 95.2 to 196.1μg/mL. In conclusion, an enhancement of the antioxidant and starch hydrolase inhibitory potential of the herbal teas was observed by adding the tea fungus., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Eighteen edible plants were assessed for their antioxidant potential based on oxygen radical absorbance capacity (ORAC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, total phenolics, vitamin C content and various lipophilic antioxidants. The inhibitory activities of the plant extracts against the enzymatic activities of α-amylase and α-glucosidase were also evaluated., Results: The antioxidant and starch hydrolase activities of the plants varied widely across a single batch of analysis. The ORAC and DPPH radical scavenging EC50 values varied between 298 and 1984 Trolox equivalents g(-1) fresh weight and between 91 and 533 mg kg(-1) fresh weight, respectively. The total phenolics and vitamin C contents varied between 32 and 125 mg gallic acid equivalents g(-1) fresh weight and between 96 and 285 µg g(-1) fresh weight, respectively. All the plants contained neoxanthin, violaxanthin, and α- and β-carotene in varying amounts. Coccinia grandis, Asparagus racemosus, Costus speciosus, Amaranthus viridis and Annona muricata displayed the highest inhibitory activities against starch hydrolases. They were the most efficient against the breakdown of seven starches exposed to the two enzymes as well., Conclusions: Overall, the edible plants were observed to display a high antioxidant potential with starch hydrolase inhibitory properties, which were beneficial in their being recognized as functional food., (© 2014 Society of Chemical Industry.)

The total phenolics contents, total antioxidant capacity (TAC) and starch hydrolase inhibitory activity of the aqueous extracts of 10 edible plants and the stability of these parameters after the gastric and duodenal digestion in an in vitro model was investigated. The TAC was evaluated using the oxygen radical absorbance capacity (ORAC) assay, ferric reducing antioxidant power (FRAP) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH•) and 2, 2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+) radical scavenging assays. Characterization and quantification of five polyphenol compounds which were previously identified to be present in all the selected plants were carried out. None of the extracts showed a decrease in the total phenolics content or the ORAC and FRAP values following digestion. None of the quantified phenolic compounds had decreased during any of the digestion phases - an observation which was deemed as beneficial in terms of therapeutic properties. Overall, the parameters analyzed were relatively stable throughout the digestive process in all the extracts.

The antioxidant and starch hydrolase inhibitory activities of cardamom, cloves, coriander, cumin seeds, curry leaves, fenugreek, mustard seeds, nutmeg, sweet cumin, and star anise extracts were investigated in an in vitro model of digestion mimicking the gastric and duodenal conditions. The total phenolic contents in all spice extracts had statistically significantly (P < 0.05) increased following both gastric and duodenal digestion. This was also in correlation with the antioxidant assays quantifying the water-soluble antioxidant capacity of the extracts. The lipophilic Oxygen Radical Absorbance Capacity assay did not indicate a statistically significant change in the values during any of the digestion phases. Statistically significant (P < 0.05) reductions in the anthocyanin contents were observed during the digestion phases in contrast to the carotenoid contents. With the exception of the cumin seed extract, none of the spice extracts showed statistically significant changes in the initial starch hydrolase enzyme inhibitory values prior to gastric and duodenal digestion. In conclusion, this study was able to prove that the 10 spices were a significant source of total phenolics, antioxidant, and starch hydrolase inhibitory activities.

The Regional Child Survival Strategy (RCSS) was launched by the World Health Organization and United Nations Children's Fund in 2006. This initially involved the six highest mortality burden countries in the region (Cambodia, China, Laos PDR, Papua New Guinea, Philippines and Vietnam). This paper aimed to describe the experiences of countries in the region in adopting and implementing the RCSS, and to identify factors that promote and impede progress. Child mortality has fallen substantially since 1990, and the region as a whole is on track to achieve the Millennium Development Goal 4 (MDG-4) targets. Some countries have made slower progress and are struggling. There is an urgent need to support countries that have, until now, not been included in the RCSS, particularly smaller Pacific Island nations, and to provide greater support to the poorest countries if MDG-4 targets for the region are to be achieved., (© 2010 The Authors. Journal of Paediatrics and Child Health © 2010 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)