Evaluation of pulmonary and systemic toxicity following lung exposure to graphite nanoplates: a member of the graphene-based nanomaterial family

Background: Graphene, a monolayer of carbon, is an engineered nanomaterial (ENM) with physical and chemical properties that may offer application advantages over other carbonaceous ENMs, such as carbon nanotubes (CNT). The goal of this study was to comparatively assess pulmonary and systemic toxicity of graphite nanoplates, a member of the graphene-based nanomaterial family, with respect to nanoplate size. Methods: Three sizes of graphite nanoplates [20 μm lateral (Gr20), 5 μm lateral (Gr5), and \u3c2 \u3eμm lateral (Gr1)] ranging from 8–25 nm in thickness were characterized for difference in surface area, structure,, zeta potential, and agglomeration in dispersion medium, the vehicle for in vivo studies. Mice were exposed by pharyngeal aspiration to these 3 sizes of graphite nanoplates at doses of 4 or 40 μg/mouse, or to carbon black (CB) as a carbonaceous control material. At 4 h, 1 day, 7 days, 1 month, and 2 months post-exposure, bronchoalveolar lavage was performed to collect fluid and cells for analysis of lung injury and inflammation. Particle clearance, histopathology and gene expression in lung tissue were evaluated. In addition, protein levels and gene expression were measured in blood, heart, aorta and liver to assess systemic responses. Results: All Gr samples were found to be similarly composed of two graphite structures and agglomerated to varying degrees in DM in proportion to the lateral dimension. Surface area for Gr1 was approximately 7-fold greater than Gr5 and Gr20, but was less reactive reactive per m2 . At the low dose, none of the Gr materials induced toxicity. At the high dose, Gr20 and Gr5 exposure increased indices of lung inflammation and injury in lavage fluid and tissue gene expression to a greater degree and duration than Gr1 and CB. Gr5 and Gr20 showed no or minimal lung epithelial hypertrophy and hyperplasia, and no development of fibrosis by 2 months post-exposure. In addition, the aorta and liver inflammatory and acute phase genes were transiently elevated in Gr5 and Gr20, relative to Gr1. Conclusions: Pulmonary and systemic toxicity of graphite nanoplates may be dependent on lateral size and/or surface reactivity, with the graphite nanoplates \u3e 5 μm laterally inducing greater toxicity which peaked at the early time points post-exposure relative to the 1–2 μm graphite nanoplate

Genetic Diversity and Population Structure of the Secondary Symbiont of Tsetse Flies, Sodalis glossinidius, in Sleeping Sickness Foci in Cameroon

Human African trypanosomiasis remains a threat to the poorest people in Africa. The trypanosomes causing the disease are transmitted by tsetse flies. The drugs currently used are unsatisfactory: some are toxic and all are difficult to administer. Furthermore, drug resistance is increasing. Therefore, investigations for novel disease control strategies are urgently needed. Previous analyses showed the association between the presence of Glossina symbiont, Sodalis glossinidius, and the fly infection by trypanosomes in a south-western region in Cameroon: flies harbouring symbionts had a threefold higher probability of being infected by trypanosomes than flies devoid of symbionts. But the study also showed substantial differences in S. glossinidius and trypanosome infection rates between Glossina populations from two Cameroonian foci of sleeping sickness. We hypothesized that the geographical isolation of the two foci may have induced the independent evolution of each one, leading to the diversification of symbiont genotypes. Microsatellite markers were used and showed that genetic diversity structuring of S. glossinidius varies at different geographical scales with a low but significant differentiation between the Campo and Bipindi HAT foci. This encourages further work on interactions between S. glossinidius subpopulations and Glossina species that could favor tsetse fly infections by a given trypanosome species

Does sexual functioning improve with migraine improvements and/or weight loss?—A post hoc analysis in the Women's Health and Migraine (WHAM) trial

Summary Background Despite plausibility of migraine headaches contributing to impaired sexual function among women, data are inconsistent and point to obesity as a potential confounder. Prospective studies that assess the relative importance of migraine improvements and weight loss in relation to sexual function could help elucidate associations among migraine, obesity and female sexual dysfunction (FSD). Objective To evaluate sexual function changes and predictors of improvement after behavioural weight loss (BWL) intervention for migraine or migraine education (ME). Methods Women with migraine and overweight/obesity were randomized to 16 weeks of BWL (n = 54) or ME (n = 56). Participants completed a 4‐week smartphone headache diary and the Female Sexual Function Index (FSFI) at pre‐ and post‐treatment. A validated FSFI total cut‐off score defined FSD. We compared changes in FSFI scores and FSD rates between conditions and evaluated migraine improvements and weight loss as predictors of sexual functioning in the full sample. Results Among treatment completers (n = 85), 56 (65.9%) participants who reported sexual activity at pre‐ and post‐treatment were analysed. Migraine improvements were similar between conditions, whereas BWL had greater weight losses compared with ME. FSD rates did not change overall (48.2% to 44.6%, p = .66) or by condition (BWL: 56.0% to 40.0% vs. ME: 41.9% to 48.4%, p = .17). Similar patterns were observed for changes in FSFI total and subscale scores. Across conditions, larger weight losses predicted greater improvements in FSFI total and arousal subscale scores, whereas larger migraine headache frequency reductions predicted greater improvements in FSFI satisfaction subscale scores. Conclusion Sexual functioning did not improve with either BWL or ME despite migraine headache improvements in both conditions and weight loss after BWL. However, weight loss related to improvements in physiological components of the sexual response (i.e., arousal) and overall sexual functioning, whereas reduced headache frequency related to improved sexual satisfaction. Additional research with larger samples is needed

Deafness and retinal degeneration in a novel USH1C knock-in mouse model

Usher syndrome is the leading cause of combined deaf - blindness, but the molecular mechanisms underlying the auditory and visual impairment are poorly understood. Usher I is characterized by profound congenital hearing loss, vestibular dysfunction, and progressive retinitis pigmentosa beginning in early adolescence. Using the c.216G>A cryptic splice site mutation in Exon 3 of the USH1C gene found in Acadian Usher I patients in Louisiana, we constructed the first mouse model that develops both deafness and retinal degeneration. The same truncated mRNA transcript found in Usher 1C patients is found in the cochleae and retinas of these knock-in mice. Absent auditory-evoked brainstem responses indicated that the mutant mice are deaf at 1 month of age. Cochlear histology showed disorganized hair cell rows, abnormal bundles, and loss of both inner and outer hair cells in the middle turns and at the base. Retinal dysfunction as evident by an abnormal electroretinogram was seen as early as 1 month of age, with progressive loss of rod photoreceptors between 6 and 12 months of age. This knock-in mouse reproduces the dual sensory loss of human Usher I, providing a novel resource to study the disease mechanism and the development of therapies