Resistin, Elastase, and Lactoferrin as Potential Plasma Biomarkers of Pediatric Inflammatory Bowel Disease Based on Comprehensive Proteomic Screens.

Inflammatory bowel disease (IBD) is an immune-mediated chronic inflammation of the intestine, which can present in the form of ulcerative colitis (UC) or as Crohn's disease (CD). Biomarkers are needed for reliable diagnosis and disease monitoring in IBD, especially in pediatric patients. Plasma samples from a pediatric IBD cohort were interrogated using an aptamer-based screen of 1322 proteins. The elevated biomarkers identified using the aptamer screen were further validated by ELISA using an independent cohort of 76 pediatric plasma samples, drawn from 30 CD, 30 UC, and 16 healthy controls. Of the 1322 proteins screened in plasma from IBD patients, 129 proteins were significantly elevated when compared with healthy controls. Of these 15 proteins had a fold change greater than 2 and 28 proteins had a fold change >1.5. Neutrophil and extracellular vesicle signatures were detected among the elevated plasma biomarkers. When seven of these proteins were validated by ELISA, resistin was the only protein that was significantly higher in both UC and CD (p < 0.01), with receiver operating characteristic area under the curve value of 0.82 and 0.77, respectively, and the only protein that exhibited high sensitivity and specificity for both CD and UC. The next most discriminatory plasma proteins were elastase and lactoferrin, particularly for UC, with receiver operating characteristic area under the curve values of 0.74 and 0.69, respectively. We have identified circulating resistin, elastase, and lactoferrin as potential plasma biomarkers of IBD in pediatric patients using two independent diagnostic platforms and two independent patient cohorts.

Repositioning Glibenclamide in cardiac fibrosis by targeting TGF-ß1-pSmad2/3-NLRP3 cascade.

The proposed objective of this study is to attenuate cardiac fibrosis by inhibiting NLRP3 inflammasome and related genes in uninephrectomized-DOCA fed rat model. Cardiac fibrosis was induced in male Sprague Dawley rats by uninephrectomy and by subsequent administration of deoxycorticosterone acetate (DOCA) every 4th day till 28 days along with 1% NaCl in drinking water. Further, the animals in treatment groups were treated with Glibenclamide (10, 20 and 40 mg/kg) for 28 days which was selected based on docking study. Interim analysis was carried out on the 14th day to assess the hemodynamic parameters. On the 28th day, anthropometric, hemodynamic, biochemical and oxidative stress parameters, gene expression (TGF-ß1, pSmad 2/3, NLRP3, IL-1ß and MMP-9), ex vivo Langendorff studies and Masson's trichrome staining of heart was carried out. Results were interpreted using ANOVA followed by post hoc Bonferroni test. Glibenclamide treatment significantly reduced the increase in blood pressure. Furthermore, the ECG patterns of the treatment groups displayed a lower frequency of the slow repolarizing events seen in the model animals. Moreover, Glibenclamide treatment demonstrated normal LV function as evidenced by a significant decrease in LVEDP. Besides, this intervention improved the anthropometric parameters and less collagen deposition in Masson's trichrome staining. The cascade of TGF-ß1-pSmad2/3-NLRP3 was downregulated along with suppression of IL-1ß. Our study repositioned anti-diabetic drug Glibenclamide to treat cardiac fibrosis by inhibiting the TGF-ß1-pSmad2/3-NLRP3 cascade.

Highly Active and Dispersed Pd Nanoparticles Stabilized by Lacunary Phosphomolybdate: Synthesis, Characterization, and Liquid Phase Hydrogenation of Levulinic Acid to γ-Valerolactone.

In the current scenario, one of the crucial reaction conversions is the synthesis of renewable biofuels and value-added chemicals from the hydrogenation of biomass. Therefore, in the present work, we are proposing aqueous phase conversion of levulinic acid to γ-valerolactone via hydrogenation using formic acid as a sustainable green hydrogen source over a sustainable heterogeneous catalyst. The catalyst based on Pd nanoparticles stabilized by lacunary phosphomolybdate (PMo11Pd) was designed for the same and characterized by EDX, FT-IR, 31P NMR, powder XRD, XPS, TEM, HRTEM, and HAADF-STEM analyses. A detailed optimization study was done to achieve maximum conversion (95% conversion), using a very small amount of Pd (1.879 × 10-3 mmol) with notable TON (2585) at 200 °C in 6 h. The regenerated catalyst was found to be workable (reusable) up to three cycles without any change in activity. Also, a plausible reaction mechanism was proposed. The catalyst exhibits superior activity against reported catalysts.

A photo-responsive fluorescent amphiphile for target-specific and image-guided drug delivery applications.

Multifunctional drug delivery systems are the centerpiece of effective chemotherapeutic strategies. Herein, we report the synthesis of an acetazolamide-linked cyanine-3-based NIR-responsive fluorescent macrocyclic amphiphile that self-assembled into spherical nanostructures in the aqueous medium via a J-aggregation pattern. The amphiphile shows various favorable properties of lipids. The photocleavage of the strained dioxacycloundecine ring induces spherical to nanotubular self-assembly with concomitant release of an encapsulated anticancer drug, doxorubicin (Dox), in a controlled manner. The CA-IX targeted amphiphile also showed lower cytotoxicity, effective cellular uptake, and Dox delivery to the model carcinoma cells.

Increased galactose expression and enhanced clearance in patients with low von Willebrand factor.

Glycan determinants on von Willebrand factor (VWF) play critical roles in regulating its susceptibility to proteolysis and clearance. Abnormal glycosylation has been shown to cause von Willebrand disease (VWD) in a number of different mouse models. However, because of the significant technical challenges associated with accurate assessment of VWF glycan composition, the importance of carbohydrates in human VWD pathogenesis remains largely unexplored. To address this, we developed a novel lectin-binding panel to enable human VWF glycan characterization. This methodology was then used to study glycan expression in a cohort of 110 patients with low VWF compared with O blood group-matched healthy controls. Interestingly, significant interindividual heterogeneity in VWF glycan expression was seen in the healthy control population. This variation included terminal sialylation and ABO(H) blood group expression on VWF. Importantly, we also observed evidence of aberrant glycosylation in a subgroup of patients with low VWF. In particular, terminal α(2-6)-linked sialylation was reduced in patients with low VWF, with a secondary increase in galactose (Gal) exposure. Furthermore, an inverse correlation between Gal exposure and estimated VWF half-life was observed in those patients with enhanced VWF clearance. Together, these findings support the hypothesis that loss of terminal sialylation contributes to the pathophysiology underpinning low VWF in at least a subgroup of patients by promoting enhanced clearance. In addition, alterations in VWF carbohydrate expression are likely to contribute to quantitative and qualitative variations in VWF levels in the normal population. This trial was registered at www.clinicaltrials.gov as #NCT03167320.

Chiral Phosphotungstate Functionalized with (S)-1-Phenylethylamine: Synthesis, Characterization, and Asymmetric Epoxidation of Styrene.

In the present work, an attempt has been made to induce chirality in copper-substituted phosphotungstate (PW11Cu) by functionalization with (S)-(+)-1-phenylethylamine (S-PEA) via a ligand substitution approach. The formation of a N→Cu dative bond was confirmed by 13C NMR, while 1H NMR, circular dichroism spectroscopy and optical rotation studies confirmed the introduction of chirality to the Keggin structure. The synthesized material was used as the heterogeneous catalyst for the asymmetric epoxidation of styrene using various green oxidants to obtain high enantiomeric excess (ee), and the reaction with molecular oxygen was found to give the best ee. Regeneration studies were carried out, and the catalyst was found to be suitable for the same. A probable mechanism is also proposed. A comparison with other copper-based polyoxometalate catalysts clearly demonstrate the superiority and novelty of the present catalyst in terms of the reaction conditions as well as the obtained ee.

Cerebrovascular Accident and SARS-CoV-19 (COVID-19): A Systematic Review.

BACKGROUND: While the most common neurologic symptoms reported in patients affected by SARS-CoV-2 are headache, dizziness, myalgia, mental fog, and anosmia, there is a growing basis of published peer-reviewed cases reporting stroke in the setting of SARS-CoV-2 infection. The peer-reviewed literature suggests an increased risk of cerebrovascular accident (CVA) in the setting of COVID-19 infection. METHODS: We searched 3 databases (PubMed, MEDLINE, and CINAHL) with search terms COVID-19, novel coronavirus, stroke, and cerebrovascular accident. Case series and case studies presenting patients positive for both COVID-19 and CVA published from January 1 through September 1, 2020, were included. Data collection and analysis was completed and risk of bias assessed. RESULTS: The search identified 28 studies across 7 counties comprising 73 patients. Amongst patients hospitalized for COVID-19 infection and CVA, the average age was 60; the most common preexisting conditions were hypertension and diabetes mellitus, and those without preexisting conditions were significantly younger with an average age of 47. Amongst hospitalized patients with COVID-19 and CVA, there was a bimodal association with COVID-19 infection severity with majority of patients classified with mild or critical COVID-19 infection. DISCUSSION: The data suggest SARS-CoV-2 is a risk factor for developing stroke, particularly in patients with hypertension and diabetes. Furthermore, the younger average age of stroke in patients with SARS-CoV-2, particularly those patients with zero identifiable preexisting conditions, creates high suspicion that SARS-CoV-2 is an independent risk factor for development of stroke; however, this cannot yet be proven without comparable control population. The data suggest the risk of developing CVA in the setting of COVID-19 infection is not dependent upon severity of illness. Continued studies must be done to understand the epidemiologic factors of COVID-19 infection and stroke and the pathophysiology of the COVID-associated hypercoagulable state.

Social Media in Minimally Invasive Gynecologic Surgery: What Is #Trending on Instagram?

STUDY OBJECTIVE: Patients share and obtain healthcare-related information on social media platforms. We aim to evaluate the authorship and content of, as well as engagement with, gynecologic topics posted on Instagram. DESIGN: Qualitative and quantitative retrospective content analysis. SETTING: Instagram. PATIENTS: Not applicable. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: A query of endometriosis, adenomyosis, myomas, and hysterectomy yielded 237 hashtags. The top 10 and most recent 20 posts, as determined by Instagram's internal algorithm, were evaluated for 10 hashtags with the most posts. The most popular topic was endometriosis. Of the 300 posts evaluated, 97.3% were by authored by nonhealthcare individuals. The most common content for nonhealthcare authored posts was personal experience (30.67%). Educational content accounted for 4.6% posts and had the greatest average engagement by number of "likes;" 0 educational posts were authored by a healthcare provider. CONCLUSION: The majority of minimally invasive gynecologic surgery related Instagram posts are regarding endometriosis, are authored by patients, and discuss personal experience. Official healthcare presence was lacking.

Developmental Outcomes of Children Born with Neonatal Abstinence Syndrome (NAS): A Scoping Review.

AIMS: The purpose of this scoping review is to provide an overview of developmental outcomes of children diagnosed with neonatal abstinence syndrome (NAS). METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework was used to guide this scoping review. A comprehensive search of CINAHL, MEDLINE, EMBASE, Web of Science, and PsycINFO was conducted using search terms related to NAS and developmental areas. Full-text screening was completed for 30 articles, and eight studies were included in this review. RESULTS: Cognitive and language development, as well as school performance, social and motor domains, may be areas of concern in children with NAS. CONCLUSIONS: The developmental outcomes of infants with NAS cannot be firmly determined due to inconsistent results across reviewed studies. Future research investigating development across various ages is required for rending more appropriate intervention services to this high-risk population.

Benzylic Hydroperoxidation via Visible-Light-Induced Csp3-H Activation.

A highly efficient benzylic hydroperoxidation has been realized through a visible-light-induced Csp3-H activation. We believe that this reaction undergoes a direct HAT mechanism catalyzed by eosin Y. This approach features the use of a metal-free catalyst (eosin Y), an energy-economical light source (blue LED), and a sustainable oxidant (molecular oxygen). Primary, secondary, and tertiary hydroperoxides as well as silyl, benzyl, and acyl peroxides were successfully prepared with good yields and excellent functional group compatibility.

Multi-stimuli controlled release of a transmembrane chloride ion carrier from a sulfonium-linked procarrier.

In recent times, anion transporters have received substantial consideration due to their ability to disrupt the ionic equilibrium across membrane bilayers. While numerous Cl- ion transporters were developed for channelopathies, unfortunately, poor aqueous solubility precluded their bioapplicability. Herein, we demonstrate the development of a multi-stimuli activatable anion transport approach to induce regulated transport of Cl- ions across membranes under specific conditions. The sulfonium-based procarrier was initially inactive, but the transmembrane transport of Cl- ions was activated in the presence of stimuli such as glutathione (GSH), reactive oxygen species (ROS) and light. The release of the hydrophobic anionophore from the aqueous-soluble procarrier under specific conditions leads to the successful transport of Cl- ions. Under physiological conditions, these anion carriers follow an antiport exchange mechanism to transport Cl- ions across lipid bilayers. Such multi-stimuli activatable procarriers have great potential to combat various types of channelopathies, including cancer, cystic fibrosis, kidney stones, myotonia, and others.

Using fundraising incentives and point-of-purchase nutrition promotion to improve food choices among school families in restaurants: a pilot and feasibility study.

OBJECTIVE: To assess the feasibility and efficacy of in-restaurant interventions aiming to promote healthy choices via fundraising incentives benefiting school wellness programmes and point-of-purchase nutrition promotion. DESIGN: Twelve schools were randomly assigned to one of the two intervention periods: Fundraising Incentive (FI) donated funds for visiting the study restaurant and Fundraising-Healthy Eating Incentive (F-HEI) included FI with additional funds given when selecting a healthier item. Both conditions included point-of-purchase nutrition promotions. Families were recruited to attend their designated intervention and complete a survey. Feasibility was assessed based on recruitment and participation, implementation fidelity and intervention acceptability. Efficacy was assessed by comparing participant receipts between intervention periods and by comparing overall restaurant sales during intervention v. two no-intervention time frames. SETTING: Fast-casual restaurant in Southern California. PARTICIPANTS: Parents with children attending participating schools. RESULTS: Eighty-one families visited the restaurant during the intervention, with sixty-six completing surveys. All study activities were implemented successfully, but school family participation in the intervention was low (0·95 %). Among participants completing surveys, all indicated satisfaction with the programme. The percentage of healthier items ordered was significantly greater during both FI (χ2 = 5·97, P = 0·01) and F-HEI (χ2 = 8·84, P = 0·003) v. Comparison 2. Results were similar but did not reach statistical significance when comparing the interventions to Comparison 1. CONCLUSIONS: Results support potential efficacy of this programme, but more research is needed to inform feasibility. Fidelity and acceptability data supported feasibility, but participation rates were low in this initial study. Methods evaluating this intervention with a greater proportion of parents should be considered.

Recent insights into HSV infection and disease: results of wider genome analysis.

PURPOSE OF REVIEW: Technology to rapidly determine the partial or full genomic sequences of large viruses has developed rapidly in the last few years. Required sample sizes have diminished and sequencing of directly collected patient samples is now possible. Using banked samples from a number of clinical studies researchers have investigated how genomic variation may determine pathogenicity and answering important questions around the limits of vaccine therapy. RECENT FINDINGS: The natural variation in HSV-1 and HSV-2 geographically has been determined. Variation in the genes responsible for surface glycoproteins may explain the current limitations of therapy. Studies looking at genomic sequences for HSV-2 in subjects with recurrent disease and in those who took part in failed vaccine studies show that multiple HSV-2 strain infection is rare outside Africa and in those with immunodeficiency, whereas there is no evidence that vaccination drives viral evolution. Genome wide association studies have investigated rates of HSV shedding have failed to identify the link between subject genomic sequence and the severity. SUMMARY: These studies will help develop better diagnostics and vaccines that are likely to be more widely effective. The findings will help counsel patients. The factors determining HSV disease severity in individuals remain elusive.

Identification of PfENR inhibitors: A hybrid structure-based approach in conjunction with molecular dynamics simulations.

In the current study, we have constructed receptor-based pharmacophore models by exploiting the Plasmodium falciparum enoyl-acyl carrier protein reductase (PfENR) structural proteome. The derived models were subjected to a series of validation procedures to list the representative hypotheses that can be used for the screening of the Drug-like Diverse Database. A set of 739 molecules was retrieved and analyzed for the adsorption, distribution, metabolism, excretion and toxicity (ADMET) and drug-likeness attributes. The filtered drug-like molecules (64) were then subjected to molecular docking and HYDE assessment studies. The hybrid structure-based approach yielded 4 molecules, UKR1308259, ENA1096786, UKR403454, and ASI51224, as PfENR inhibitors. The stability of these inhibitors was assessed using molecular mechanics-generalized born surface area approach-based free binding energy calculations and molecular dynamics simulations. Molecular mechanics-generalized born surface area calculations and molecular dynamics simulations showed that UKR1308259, ENA1096786, and ASI51224 were more potent PfENR inhibitors. The rationale behind the current work was to identify orally available inhibitor molecules with diverse scaffolds that could serve as initial leads for the drug design against PfENR.

Promoting healthier children's meals at quick-service and full-service restaurants: Results from a pilot and feasibility study.

High-calorie restaurant foods contribute to childhood overweight. Increased consumer demand for healthier kids' meals may motivate the restaurant industry to provide additional healthy options. This study pilot-tested a combination of four strategies (toy incentive, placemats, server prompts, signage) designed to increase demand for healthier kids' meals, which were defined as those eligible for the National Restaurant Association's Kids LiveWell program. Relative sales of healthier kids' meals were examined before (n = 3473 total kids' meal orders) and during Month 1 (n = 3546 total kids' meal orders) and Month 2 of implementation (n = 3645 total kids' meal orders) of an 8-week intervention in two locations each of a quick-service (QSR) and full-service (FSR) restaurant chain. Convenience samples of children (n = 27) and their parents (n = 28) were surveyed regarding parent and child perceptions of intervention components. Findings regarding the effectiveness and feasibility of the intervention were mixed. At the FSRs, the relative percentage of monthly sales from healthier kids' meals increased from 5.0% of kids' meal orders at baseline to 8.3% during Month 1, ending at 6.4% during Month 2. At the QSRs, the relative percentage of monthly sales from healthier kids' entrees decreased from 27.5% at baseline to 25.2% during Month 1, ending at 25.9% during Month 2. Implementation quality tracking showed that consistent implementation of intervention components was a challenge; parent- and child-reported awareness of intervention components supported this finding. Future directions are discussed, aiming to build upon these findings and maximize the feasibility, effectiveness, and sustainability of efforts to promote healthier eating in restaurants.

Higher Levels of Caregiver Strain Perceived by Indian Mothers of Children and Young Adults with Cerebral Palsy Who have Limited Self-Mobility.

AIM: Describe and compare the caregiver strain experienced among Indian mothers of children and young adults with cerebral palsy (CP) living in low resource settings. METHODS: 62 consecutive children and young adults with spastic CP (mean age 6.0 ± 4.5, range 2-21) and their parents were recruited from an outpatient physiotherapy department for this cross-sectional study. Ability to walk was classified using the Gross Motor Function Classification System and mother's caregiver strain was measured using caregiver strain index (CSI). RESULTS: Mothers of children and young adults who have limited self-mobility perceived higher caregiver strain (mean CSI score 12.0 ± 1.3, p < 0.05) than mothers of children who can walk (mean CSI score 4.5 ± 3.0, p < 0.05). All 46 mothers of children and youth in GMFCS levels IV and V reported high levels of caregiver stress compared with only three of 16 mothers of children and youth who walk (levels I and II). CONCLUSIONS: Physiotherapists and occupational therapists serving children and youth with CP are encouraged to partner with families to identify goals for ease of caregiving, activity, and participation at home and in the community.

Mixed Messages: Ambiguous Penalty Information in Modified Restaurant Menu Items.

Restaurant menu items from six national or regional brands were modified to reduce fat, saturated fat, sodium and total calories. Twenty-four items were tested with a current recipe, and two modifications (small and moderate reductions) for 72 total products. Approximately 100 consumers tested each product for acceptability as well as for desired levels of tastes/flavor, amounts of key ingredients and texture/consistency using just-about-right (JAR) scales. Penalty analysis was conducted to assess the effects of non-JAR ratings on acceptability scores. Situations arose where JAR ratings and penalty analyses could yield different recommendations, including large groups with low penalties and small groups with high penalties. Opposing groups with moderate to high penalties on opposite sides of the same JAR scale were also seen. Strategies for dealing with these observances are discussed.

Cognitive Profile of C9orf72 in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

This review article focuses on the cognitive profile associated with the C9orf72 gene with GGGGCC (G4C2) hexanucleotide repeat expansions that is commonly found in both familial and sporadic forms of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) in order to aid clinicians in the screening process. In this growing clinical continuum between FTD and ALS, understanding and recognizing a neurocognitive profile is important for diagnosis. Key features of this profile include executive dysfunction with memory impairment and language deficits as the disease progresses. Behaviorally, patients are prone to disinhibition, apathy, and psychosis. With the discovery of this mutation, studies have begun to characterize the different phenotypes associated with this mutation in terms of epidemiology, clinical presentation, imaging, and pathology. Greater awareness and increased surveillance for this mutation will benefit patients and their families in terms of access to genetic counseling, research studies, and improved understanding of the disease process.

A Case of Lemierre-Like Syndrome in a Pediatric Patient.

Lemierre-like syndrome is a rare, systemic sequelae following a persistent oropharyngeal infection, leading to septic thrombophlebitis of the internal jugular vein (IJV). Lemierre syndrome is caused by the obligate anaerobic organism Fusobacterium necrophorum, innate to the oropharyngeal tract. Lemierre-like syndrome is due to infections caused by other organisms, including methicillin-resistant Staphylococcus aureus (MRSA). We are reporting a case of a five-month-old male who presented with one week of fever that was not alleviated by acetaminophen, bilateral otitis media, and left-sided cervical lymphadenopathy not alleviated with medical therapy. The patient's clinical course continued to deteriorate as he developed respiratory distress that progressed to acute respiratory failure requiring mechanical ventilation support. Extensive laboratory investigation ruled out the causes of primary and secondary immunodeficiencies. Blood cultures were positive for MRSA, and he was treated initially with vancomycin, then switched to linezolid per ENT recommendations, and ultimately needed daptomycin and ceftaroline therapy. A computed tomography (CT) scan of the neck and chest showed deep neck space infection, bilateral loculated pleural empyema, and mediastinitis. The patient required a decortication video-assisted thoracoscopic surgery (VATS), multiple drains, and a mediastinal washout to control the MRSA infection. This report emphasizes that the rapid progression and spread of septic thrombus can become detrimental to a patient's recovery and survival; therefore, it should be recognized early and treated promptly.

Sulfonium-Cross-Linked Hyaluronic Acid-Based Self-Healing Hydrogel: Stimuli-Responsive Drug Carrier with Inherent Antibacterial Activity to Counteract Antibiotic-Resistant Bacteria.

Augmentation of the activity of Food and Drug Administration-approved antibiotics by an adjuvant or antibiotic carrier is considered one of the promising strategies to fight against antibiotic-resistant bacteria. This study reports the development of sulfonium-cross-linked hyaluronic acid (HA)-based polymer (HA-SS-HA) as an inherent antimicrobial agent and antibiotic carrier. The HA-SS-HA polymer offers the potential for encapsulating various classes of antibiotics and accomplishing a stimuli-responsive release profile in the presence of hyaluronidase produced by bacterial cells within their extracellular environment. Systematic antibacterial studies reveal that the HA-SS-HA-encapsulated antibiotics (vancomycin, amoxicillin, and tetracycline) restore its activity against the antibiotic-resistant bacterial cells methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE), and Pseudomonas aeruginosa. The HA-SS-HA gel shows robust efficacy in eradicating the mature biofilm of Staphylococcus aureus (S. aureus). The membrane-disrupting activity reveals that HA-SS-HA can also counteract the antibiotic resistance mechanism of the bacterial cells. The in vivo studies reveal excellent wound-healing activity of HA-SS-HA in albino laboratory-bred (BALB/c) mice. The outcome of additional antibacterial studies reveals that antibiotics-encapsulated HA-SS-HA hydrogel can effectively combat Gram-negative, Gram-positive, and antibiotic-resistant bacterial strains. Therefore, revitalizing the activity of commercial antibiotics by HA-SS-HA can be considered a valuable and economically effective strategy to fight against antibiotic-resistant bacteria.