Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1

PMCID: PMC3601088This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Multi-disciplinary Insights from the First European Forum on Visceral Myopathy 2022 Meeting

Visceral myopathy is a rare, life-threatening disease linked to identified genetic mutations in 60% of cases. Mostly due to the dearth of knowledge regarding its pathogenesis, effective treatments are lacking. The disease is most commonly diagnosed in children with recurrent or persistent disabling episodes of functional intestinal obstruction, which can be life threatening, often requiring long-term parenteral or specialized enteral nutritional support. Although these interventions are undisputedly life-saving as they allow affected individuals to avoid malnutrition and related complications, they also seriously compromise their quality of life and can carry the risk of sepsis and thrombosis. Animal models for visceral myopathy, which could be crucial for advancing the scientific knowledge of this condition, are scarce. Clearly, a collaborative network is needed to develop research plans to clarify genotype–phenotype correlations and unravel molecular mechanisms to provide targeted therapeutic strategies. This paper represents a summary report of the first ‘European Forum on Visceral Myopathy’. This forum was attended by an international interdisciplinary working group that met to better understand visceral myopathy and foster interaction among scientists actively involved in the field and clinicians who specialize in care of people with visceral myopathy. Graphical Abstract: [Figure not available: see fulltext.

Health Care Provider Knowledge and Practices Regarding Folic Acid, United States, 2002–2003

Objective: To assess health care providers (HCP) knowledge and practices regarding folic acid (FA) use for neural tube defect (NTD) prevention. Methods: Two identical surveys were conducted among 611 obstetricians/gynecologists (OB/GYNs) and family/general physicians (FAM/GENs) (2002), and 500 physician assistants (PAs), nurse practitioners (NPs), certified nurse midwives (CNMs), and registered nurses (2003) to ascertain knowledge and practices regarding FA. For analysis, T-tests, univariate and multivariate logistic regression modeling were used. Results: Universally, providers knew that FA prevents birth defects. Over 88% knew when a woman should start taking folic acid for the prevention of NTDs; and over 85% knew FA supplementation beyond what is available in the diet is necessary. However, only half knew that 50% of all pregnancies in the United States are unplanned. Women heard information about multivitamins or FA most often during well woman visits in obstetrical/gynecology (ob/gyn) practice settings (65%), and about 50% of the time during well woman visits in family/general (fam/gen) practice settings and 50% of the time at gynecology visits (both settings). Among all providers, 42% did not know the correct FA dosage (400 μg daily). HCPs taking multivitamins were more than twice as likely to recommend multivitamins to their patients (Odds Ratio [OR] 2.27 95%, Confidence Interval [CI] 1.75–2.94). HCPs with lower income clients (OR 1.49, CI 1.22–1.81) and HCPs with practices having more than 10% minorities (OR 1.46, CI 1.11–1.92) were more likely to recommend supplements. NPs in ob/gyn settings were most likely and FAM/GENs were least likely to recommend supplements (OR 3.06, CL 1.36–6.90 and OR 0.64, CL 0.45–0.90 respectively). Conclusions: Knowledge about birth defects and the necessity of supplemental FA was high. Increasing knowledge about unintended pregnancy rates and correct dosages of FA is needed. The strongest predictor for recommending the use of FA supplements was whether the provider took a multivitamin

Using Magnetically Responsive Tea Waste to Remove Lead in Waters under Environmentally Relevant Conditions

We report the use of a simple yet highly effective magnetite-waste tea composite to remove lead(II) (Pb[superscript 2+]) ions from water. Magnetite-waste tea composites were dispersed in four different types of water–deionized (DI), artificial rainwater, artificial groundwater and artificial freshwater–that mimic actual environmental conditions. The water samples had varying initial concentrations (0.16–5.55 ppm) of Pb[superscript 2+] ions and were mixed with the magnetite-waste tea composite for at least 24 hours to allow adsorption of the Pb[superscript 2+] ions to reach equilibrium. The magnetite-waste tea composites were stable in all the water samples for at least 3 months and could be easily removed from the aqueous media via the use of permanent magnets. We detected no significant leaching of iron (Fe) ions into the water from the magnetite-waste tea composites. The percentage of Pb adsorbed onto the magnetite-waste tea composite ranged from ~70% to 100%; the composites were as effective as activated carbon (AC) in removing the Pb[superscript 2+] ions from water, depending on the initial Pb concentration. Our prepared magnetite-waste tea composites show promise as a green, inexpensive and highly effective sorbent for removal of Pb in water under environmentally realistic conditions.SUTD-MIT International Design Center (Research Grant IDG11200105/IDD11200109)Singapore-MIT Allianc

Sustainable Sources of Biomass for Bioremediation of Heavy Metals in Waste Water Derived from Coal-Fired Power Generation

Biosorption of heavy metals using dried algal biomass has been extensively described but rarely implemented. We contend this is because available algal biomass is a valuable product with a ready market. Therefore, we considered an alternative and practical approach to algal bioremediation in which algae were cultured directly in the waste water stream. We cultured three species of algae with and without nutrient addition in water that was contaminated with heavy metals from an Ash Dam associated with coal-fired power generation and tested metal uptake and bioremediation potential. All species achieved high concentrations of heavy metals (to 8% dry mass). Two key elements, V and As, reached concentrations in the biomass of 1543 mg.kg−1 DW and 137 mg.kg−1 DW. Growth rates were reduced by more than half in neat Ash Dam water than when nutrients were supplied in excess. Growth rate and bioconcentration were positively correlated for most elements, but some elements (e.g. Cd, Zn) were concentrated more when growth rates were lower, indicating the potential to tailor bioremediation depending on the pollutant. The cosmopolitan nature of the macroalgae studied, and their ability to grow and concentrate a suite of heavy metals from industrial wastes, highlights a clear benefit in the practical application of waste water bioremediation

Body weight dissatisfaction and communication with parents among adolescents in 24 countries: international cross-sectional survey

BACKGROUND: Parents have significant influence on behaviors and perceptions surrounding eating, body image and weight in adolescents. The aim of this study was to examine the prevalence of body weight dissatisfaction, difficulty in communication with the parents and the relationship between communication with parents and adolescents' dissatisfaction with their body weight (dieting or perceived need to diet). METHODS: Survey data were collected from adolescents in 24 countries and regions in Europe, Canada, and the USA who participated in the cross-sectional 2001/2002 Health Behaviour of School-Aged Children (HBSC) study. The association between communication with parents and body weight dissatisfaction was examined using binary logistic regression analysis. RESULTS: Body weight dissatisfaction was highly prevalent and more common among girls than boys, among overweight than non-overweight, and among older adolescents than younger adolescents. Difficulty in talking to father was more common than difficulty in talking to mother in all countries and it was greater among girls than among boys and increased with age. Difficulties in talking to father were associated with weight dissatisfaction among both boys and girls in most countries. Difficulties in talking to mother were rarely associated with body weight dissatisfaction among boys while among girls this association was found in most countries. CONCLUSION: The findings suggest that enhanced parent communication might contribute in most countries to less body dissatisfaction in girls and better communication with the father can help avoiding body weight dissatisfaction in boys. Professionals working with adolescents and their families should help adolescents to have a healthy weight and positive body image and promote effective parent – adolescent communication.peerReviewe

Synergies, Strengths and Challenges: Findings on Community Capability from a Systematic Health Systems Research Literature Review

Background: Community capability is the combined influence of a community’s social systems and collective resources that can address community problems and broaden community opportunities. We frame it as consisting of three domains that together support community empowerment: what communities have; how communities act; and for whom communities act. We sought to further understand these domains through a secondary analysis of a previous systematic review on community participation in health systems interventions in low and middle income countries (LMICs). Methods: We searched for journal articles published between 2000 and 2012 related to the concepts of “community”, “capability/participation”, “health systems research” and “LMIC.” We identified 64 with rich accounts of community participation involving service delivery and governance in health systems research for thematic analysis following the three domains framing community capability. Results: When considering what communities have, articles reported external linkages as the most frequently gained resource, especially when partnerships resulted in more community power over the intervention. In contrast, financial assets were the least mentioned, despite their importance for sustainability. With how communities act, articles discussed challenges of ensuring inclusive participation and detailed strategies to improve inclusiveness. Very little was reported about strengthening community cohesiveness and collective efficacy despite their importance in community initiatives. When reviewing for whom communities act, the importance of strong local leadership was mentioned frequently, while conflict resolution strategies and skills were rarely discussed. Synergies were found across these elements of community capability, with tangible success in one area leading to positive changes in another. Access to information and opportunities to develop skills were crucial to community participation, critical thinking, problem solving and ownership. Although there are many quantitative scales measuring community capability, health systems research engaged with community participation has rarely made use of these tools or the concepts informing them. Overall, the amount of information related to elements of community capability reported by these articles was low and often of poor quality. Conclusions: Strengthening community capability is critical to ensuring that community participation leads to genuine empowerment. Our simpler framework to define community capability may help researchers better recognize, support and assess it

The Influence of cis-Regulatory Elements on DNA Methylation Fidelity

It is now established that, as compared to normal cells, the cancer cell genome has an overall inverse distribution of DNA methylation (“methylome”), i.e., predominant hypomethylation and localized hypermethylation, within “CpG islands” (CGIs). Moreover, although cancer cells have reduced methylation “fidelity” and genomic instability, accurate maintenance of aberrant methylomes that underlie malignant phenotypes remains necessary. However, the mechanism(s) of cancer methylome maintenance remains largely unknown. Here, we assessed CGI methylation patterns propagated over 1, 3, and 5 divisions of A2780 ovarian cancer cells, concurrent with exposure to the DNA cross-linking chemotherapeutic cisplatin, and observed cell generation-successive increases in total hyper- and hypo-methylated CGIs. Empirical Bayesian modeling revealed five distinct modes of methylation propagation: (1) heritable (i.e., unchanged) high- methylation (1186 probe loci in CGI microarray); (2) heritable (i.e., unchanged) low-methylation (286 loci); (3) stochastic hypermethylation (i.e., progressively increased, 243 loci); (4) stochastic hypomethylation (i.e., progressively decreased, 247 loci); and (5) considerable “random” methylation (582 loci). These results support a “stochastic model” of DNA methylation equilibrium deriving from the efficiency of two distinct processes, methylation maintenance and de novo methylation. A role for cis-regulatory elements in methylation fidelity was also demonstrated by highly significant (p<2.2×10−5) enrichment of transcription factor binding sites in CGI probe loci showing heritably high (118 elements) and low (47 elements) methylation, and also in loci demonstrating stochastic hyper-(30 elements) and hypo-(31 elements) methylation. Notably, loci having “random” methylation heritability displayed nearly no enrichment. These results demonstrate an influence of cis-regulatory elements on the nonrandom propagation of both strictly heritable and stochastically heritable CGIs

Complexities of Assessing the Disease Burden Attributable to Leishmaniasis

Among parasitic diseases, morbidity and mortality caused by leishmaniasis are surpassed only by malaria and lymphatic filariasis. However, estimation of the leishmaniasis disease burden is challenging, due to clinical and epidemiological diversity, marked geographic clustering, and lack of reliable data on incidence, duration, and impact of the various disease syndromes. Non-health effects such as impoverishment, disfigurement, and stigma add to the burden, and introduce further complexities. Leishmaniasis occurs globally, but has disproportionate impact in the Horn of Africa, South Asia and Brazil (for visceral leishmaniasis), and Latin America, Central Asia, and southwestern Asia (for cutaneous leishmaniasis). Disease characteristics and challenges for control are reviewed for each of these foci. We recommend review of reliable secondary data sources and collection of baseline active survey data to improve current disease burden estimates, plus the improvement or establishment of effective surveillance systems to monitor the impact of control efforts

Ocular Application of the Kinin B1 Receptor Antagonist LF22-0542 Inhibits Retinal Inflammation and Oxidative Stress in Streptozotocin-Diabetic Rats

Purpose: Kinin B1 receptor (B1R) is upregulated in retina of Streptozotocin (STZ)-diabetic rats and contributes to vasodilation of retinal microvessels and breakdown of the blood-retinal barrier. Systemic treatment with B 1R antagonists reversed the increased retinal plasma extravasation in STZ rats. The present study aims at determining whether ocular application of a water soluble B1R antagonist could reverse diabetes-induced retinal inflammation and oxidative stress. Methods: Wistar rats were made diabetic with STZ (65 mg/kg, i.p.) and 7 days later, they received one eye drop application of LF22-0542 (1 % in saline) twice a day for a 7 day-period. The impact was determined on retinal vascular permeability (Evans blue exudation), leukostasis (leukocyte infiltration using Fluorescein-isothiocyanate (FITC)-coupled Concanavalin A lectin), retinal mRNA levels (by qRT-PCR) of inflammatory (B1R, iNOS, COX-2, ICAM-1, VEGF-A, VEGF receptor type 2, IL-1b and HIF-1a) and anti-inflammatory (B2R, eNOS) markers and retinal level of superoxide anion (dihydroethidium staining). Results: Retinal plasma extravasation, leukostasis and mRNA levels of B 1R, iNOS, COX-2, VEGF receptor type 2, IL-1b and HIF-1a were significantly increased in diabetic retinae compared to control rats. All these abnormalities were reversed to control values in diabetic rats treated with LF22-0542. B1R antagonist also significantly inhibited the increased production of superoxide anion in diabetic retinae. Conclusion: B1R displays a pathological role in the early stage of diabetes by increasing oxidative stress and proinflammator