Usage of nanoparticles with their potential toxicity assessment and regulatory guidelines

In recent times engineered nanoparticles have been receiving much attention from researchers due to their extensive use in a variety of chemical, biological, and industrial areas. Their physiochemical properties have led to a number of uses in commercial products. Considering their broad applications, with increasing human contact the risks of exposure are also increasing. In vivo toxicity experiments involving administering nanoparticles to living organisms have shown their adverse effects on organ development and reproduction. Nanoparticles can be considerably more toxic than the large-sized particles since they can move relatively freely compared to bulkier molecules. Henceforth, it is our duty to assess the harmful health consequences associated with human exposure to nanoparticles in order to improve safe production and use. We will review the current applications of nanoparticles, and issues related to their toxicity. We will focus on safety regulations, risk assessment and regulatory guidelines of nanoparticles. The validation and standardization of nanotoxicity tests will further promote safe applications of nanotechnology in our daily lives.     

Antibody-Secreting Cell Responses after Vibrio cholerae O1 Infection and Oral Cholera Vaccination in Adults in Bangladesh

Infection with Vibrio cholerae and oral cholera vaccines (OCVs) induce transient circulating plasmablast responses that peak within approximately 7 days after infection or vaccination. We previously demonstrated that plasmablast responses strongly correlate with subsequent levels of V. cholerae-specific duodenal antibodies up to 6 months after V. cholerae infection. Hence, plasmablast responses provide an early window into the immunologic memory at the mucosal surface. In this study, we characterized plasmablast responses following V. cholerae infection using a flow cytometrically defined population and compared V. cholerae-specific responses in adult patients with V. cholerae O1 infection and vaccinees who received the OCV Dukoral (Crucell Vaccines Canada). Among flow cytometrically sorted populations of gut-homing plasmablasts, almost 50% of the cells recognized either cholera toxin B subunit (CtxB) or V. cholerae O1 lipopolysaccharide (LPS). Using a traditional enzyme-linked immunosorbent spot assay (ELISPOT), we found that infection with V. cholerae O1 and OCVs induce similar responses to the protein antigen CtxB, but responses to LPS were diminished after OCV compared to those after natural V. cholerae infection. A second dose of OCV on day 14 failed to boost circulating V. cholerae-specific plasmablast responses in Bangladeshi adults. Our results differ from those in studies from areas where cholera is not endemic, in which a second vaccination on day 14 significantly boosts plasmablast responses. Given these results, it is likely that the optimal boosting strategies for OCVs differ significantly between areas where V. cholerae infection is endemic and those where it is not.     

Antioxidative Potential of Duranta Repens (Linn.) Fruits Against H2O2 Induced Cell Death In Vitro

The effects of Duranta repens fruits were investigated on H₂O₂ induced oxidative cell death to evaluate its antioxidative potential in vitro. HEK293T cells were treated with different concentrations [0–1000 µg/ ml] of ethanol extract (E-Ex) and methanol extract (M-Ex) of D. repens for 24h, and then treated with 100 µM H₂O₂ for 24h. Cell viability, antioxidant parameters of cells, and antioxidant constituents of the extracts were determined. Treatment with limited dose of E-Ex or M-Ex increased the survival rate of H₂O₂-treated HEK293T cells, however the extra-high dose showed growth inhibitory effect. Treatment with E-Ex or M-Ex protected cellular lipid per-oxidation. In vitro analyses showed the 2,2-diphenyl-1-picrylhydrazyl and H₂O₂ scavenging activities as well as reducing potential of the extracts. We report here that the limited dose of E-Ex and M-Ex possess antioxidative potential, which can protect H₂O₂-induced oxidative cell damage.     

Genomic Analysis Reveals Distinct Subtypes in Two Rare Cases of Primary Ovarian Lymphoma

Primary (localized) non-Hodgkin lymphoma (NHL) of the ovary is extremely rare; only a few cases have been reported in the literature. We report two cases of primary ovarian lymphoma (POL), one involving bilateral ovaries in a 15-year-old girl and other involving one ovary in a 5-year-old girl. This report describes detailed clinical, histopathological, and imaging findings, along with the review of literature of primary diffuse large B-cell lymphoma (DLBCL) arising from an ovary. In addition, we describe findings of targeted capture panel sequencing on both tumors and identify the major genetic mutations that are recurrently mutated in pan-cancers. Compared to the genomic mutation features of major subtypes of DLBCL, we distinguish that each POL belongs to distinctive subtypes, GCB (germinal center B-cell subtype) DLBCL and ABC (activated B-cell subtype) DLBCL, respectively. The findings from the genomic analysis may help to understand the pathogenesis of POL and to guide potential targeted therapy in the future.     

RAGE: a new frontier in chronic airways disease

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous inflammatory disorders of the respiratory tract characterized by airflow obstruction. It is now clear that the environmental factors that drive airway pathology in asthma and COPD, including allergens, viruses, ozone and cigarette smoke, activate innate immune receptors known as pattern-recognition receptors, either directly or indirectly by causing the release of endogenous ligands. Thus, there is now intense research activity focused around understanding the mechanisms by which pattern-recognition receptors sustain the airway inflammatory response, and how these mechanisms might be targeted therapeutically. One pattern-recognition receptor that has recently come to attention in chronic airways disease is the receptor for advanced glycation end products (RAGE). RAGE is a member of the immunoglobulin superfamily of cell surface receptors that recognizes pathogen- and host-derived endogenous ligands to initiate the immune response to tissue injury, infection and inflammation. Although the role of RAGE in lung physiology and pathophysiology is not well understood, recent genome-wide association studies have linked RAGE gene polymorphisms with airflow obstruction. In addition, accumulating data from animal and clinical investigations reveal increased expression of RAGE and its ligands, together with reduced expression of soluble RAGE, an endogenous inhibitor of RAGE signalling, in chronic airways disease. In this review, we discuss recent studies of the ligand–RAGE axis in asthma and COPD, highlight important areas for future research and discuss how this axis might potentially be harnessed for therapeutic benefit in these conditions.     

Can T1w/T2w ratio be used as a myelin‐specific measure in subcortical structures? Comparisons between FSE‐based T1w/T2w ratios,GRASE‐based T1w/T2w ratios and multi‐echo GRASE‐based myelin water fractions

Given the growing popularity of T₁‐weighted/T₂‐weighted (T₁w/T₂w) ratio measurements, the objective of the current study was to evaluate the concordance between T₁w/T₂w ratios obtained using conventional fast spin echo (FSE) versus combined gradient and spin echo (GRASE) sequences for T₂w image acquisition, and to compare the resulting T₁w/T₂w ratios with histologically validated myelin water fraction (MWF) measurements in several subcortical brain structures. In order to compare these measurements across a relatively wide range of myelin concentrations, whole‐brain T₁w magnetization prepared rapid acquisition gradient echo (MPRAGE), T₂w FSE and three‐dimensional multi‐echo GRASE data were acquired from 10 participants with multiple sclerosis at 3 T. Then, after high‐dimensional, non‐linear warping, region of interest (ROI) analyses were performed to compare T₁w/T₂w ratios and MWF estimates (across participants and brain regions) in 11 bilateral white matter (WM) and four bilateral subcortical grey matter (SGM) structures extracted from the JHU_MNI_SS ‘Eve’ atlas. Although the GRASE sequence systematically underestimated T₁w/T₂w values compared to the FSE sequence (revealed by Bland–Altman and mountain plots), linear regressions across participants and ROIs revealed consistently high correlations between the two methods (r² = 0.62 for all ROIs, r² = 0.62 for WM structures and r² = 0.73 for SGM structures). However, correlations between either FSE‐based or GRASE‐based T₁w/T₂w ratios and MWFs were extremely low in WM structures (FSE‐based, r² = 0.000020; GRASE‐based, r² = 0.0014), low across all ROIs (FSE‐based, r² = 0.053; GRASE‐based, r² = 0.029) and moderate in SGM structures (FSE‐based, r² = 0.20; GRASE‐based, r² = 0.17). Overall, our findings indicated a high degree of correlation (but not equivalence) between FSE‐based and GRASE‐based T₁w/T₂w ratios, and low correlations between T₁w/T₂w ratios and MWFs. This suggests that the two T₁w/T₂w ratio approaches measure similar facets of subcortical tissue microstructure, whereas T₁w/T₂w ratios and MWFs appear to be sensitized to different microstructural properties. On this basis, we conclude that multi‐echo GRASE sequences can be used in future studies to efficiently elucidate both general (T₁w/T₂w ratio) and myelin‐specific (MWF) tissue characteristics.     

Prevalence and Correlates of Smoking among Low-Income Adults Residing in New York City Public Housing Developments—2015

To guide targeted cessation and prevention programming, this study assessed smoking prevalence and described sociodemographic, health, and healthcare use characteristics of adult smokers in public housing. Self-reported data were analyzed from a random sample of 1664 residents aged 35 and older in ten New York City public housing developments in East/Central Harlem. Smoking prevalence was 20.8%. Weighted log-binomial models identified to be having Medicaid, not having a personal doctor, and using health clinics for routine care were positively associated with smoking. Smokers without a personal doctor were less likely to receive provider quit advice. While most smokers in these public housing developments had health insurance, a personal doctor, and received provider cessation advice in the last year (72.4%), persistently high smoking rates suggest that such cessation advice may be insufficient. Efforts to eliminate differences in tobacco use should consider place-based smoking cessation interventions that extend cessation support beyond clinical settings.