Abstract Background It has been well recognized that toxicity of fine ambient air particulate matter (PM 2.5 ) may depend on its chemical constituents, including components such as soluble metals that may theoretically exert distinctive effects. We have recently demonstrated an important effect of PM 2.5 on metabolic function. Since transition metals, such as nickel (Ni), represent an important component of exposure in certain environments, and may significantly influence the toxicity of inhalational exposure, we investigated the effects of Ni as a variable component of ambient PM 2.5 exposure. Methods Male ApoE knockout mice were exposed to filtered air (FA), fine-sized nickel sulfate particles alone (Ni) at 0.44 μ g/m 3 , concentrated ambient air PM 2.5 (CAPs) at a mean of 70 μ g/m 3 , or CAPs+Ni in Tuxedo, NY, 6 hours/day, 5 days/week, for 3 months. Results Exposure to Ni, irrespective of co-exposure to CAPs, resulted in body weight gain, while exposure to CAPs+Ni significantly enhanced fasting glucose and worsened insulin resistance measures (HOMA-IR), when compared with exposure to CAPs alone. CAPs+Ni exposure induced a significant decrease in phosphorylation of AMP-activated protein kinase (AMPK) α. Exposure to Ni or CAPs+Ni significantly induced microcirculatory dysfunction and increased monocytic cell infiltration into lung and adipose, and decreased uncoupling protein 1 expression at gene and protein levels and several brown adipocyte-specific genes in adipose tissue. Conclusions Ni exposure has effects on metabolic and inflammatory parameters that are comparable to that of CAPs. Additionally, Ni synergistically exacerbates CAPs-induced adverse effects on some of, but not all of, these parameters, that may be mediated via the AMPK signaling pathway. These findings have important implications for inhaled transition metal toxicity that may exert synergistic effects with other PM 2.5 components.
This paper reviews toxicological literature pertaining to coal combustion products (CCPs) inhalation and presents case studies on the inhalation of CCPs from the Kingston Fossil Plant area and from the Colbert Fossil Plant CCP landfill site. While most research regarding coal plant emissions focuses on fly ash, this article takes a holistic approach to examining not only emitted particulate matter such as fly ash, but also the theoretical calculated doses of landfilled CCPs. Furthermore, these doses are compared to in vitro and in vivo studies in order to highlight differences between laboratory-based studies and to emphasize the difficulty in extrapolating effects from inhalation exposures. In both case studies, fugitive emissions from the Kingston ash spill or the Colbert CCP-handling operations did not exceed any national ambient air quality standards or reference concentrations for individual components. Adverse effects such as mild pulmonary inflammation noted in the reviewed literature were in response to doses much higher than would be likely to occur in humans exposed to landfilled CCPs. We conclude that the doses for fugitive emissions calculated herein do not appear to be high enough to elicit a measurable adverse response in humans.
In addition to being the single greatest known environmental cause of cancer, cigarette smoke (CS) is also a major contributor to heart disease. We reported previously that 1) inhalation of either mainstream or sidestream CS promotes aortic arteriosclerotic plaque development; 2) 1,3 butadiene, a vapor-phase component of CS, promotes plaque development at 20 ppm, which at the time was only 2 times higher than the threshold limit value; and 3) individual tar fraction carcinogens in CS, including polynuclear aromatic hydrocarbons (PAHs) and nitrosamines, either do not promote plaque development or do so only at high concentrations. These results suggested that the tar fraction is not the primary source of plaque-promoting agents in CS. We asked whether repeated exposure to the tar fraction of CS, collected in a cold trap (TAR), promotes plaque development in an avian model of arteriosclerosis. Acetone extracts of mainstream CS tar from burning, unfiltered reference cigarettes were solubilized in dimethyl sulfoxide (DMSO) and injected weekly into cockerels for 16 weeks (25 mg/kg/week). Positive controls were injected weekly with the synthetic PAH carcinogen, 7,12 dimethylbenz(a)anthracene (DMBA) dissolved in DMSO and negative controls were injected with DMSO. Plaque location and prevalence did not differ from group to group. Morphometric analysis of plaque cross-sectional areas showed that plaque sizes, which are log-normally distributed, were significantly larger in the DMBA cockerels compared to both the TAR and DMSO groups. There were no significant differences in plaque size between DMSO and TAR cockerels. The results reported here, combined with other recent findings, support the conclusion that the primary arteriosclerotic plaque-promoting components of CS are in the vapor phase.
INTRODUCTION: Management of dystonia using Deep Brain Stimulation (DBS) is a well-established therapeutic approach. However, optimal DBS target sites in patients with cervical (focal) versus generalized dystonia are thought to diverge and be specific for particular connections (Horn 2022). DBS devices equipped with capabilities such as directionality and Multiple Independent Current Control (MICC) may offer potential for improved clinical outcomes. METHODS: This is a sub-analysis of patients with focal (cervical) dystonia only or cervical dystonia in the context of segmental or generalized dystonia assessed as part of a prospective, multicenter, international dystonia registry (NCT02686125). All patients receive an MICC-based, directional DBS system (Vercise, Boston Scientific). Patients are followed up to 3-years (post-implant). Several study assessments are being collected to evaluate their dystonia symptoms (e.g., TWSTRS), quality of life, and overall satisfaction. Adverse Events are also collected. RESULTS: A total of 43-patients (mean age 56.9-years, 58% females) with focal (cervical) dystonia only and 83 patients (mean 41.95-years, 61% females) with cervical dystonia in context of segmental or generalized dystonia have been evaluated. Both groups reported significant improvement in overall TWSTRS scores – however the extent varied. In the cervical-only cohort, a 19.9-point improvement was noted at 6-months (n = 25) and sustained up to 1-year (23.2-point improvement, n = 20). In those with cervical dystonia within frame of segmental or generalized dystonia, a 9.7-point and 7.3-point improvement in overall TWSTRS scores was noted at 6- (n = 50) and 12-months (n = 38), respectively. Updated data will be reported. CONCLUSIONS: This registry represents the first comprehensive, large-scale collection of real-world outcomes associated with dystonia patients implanted with a directional DBS system capable of MICC. Preliminary results demonstrate significant improvement in patients with cervical dystonia (alone or in context of segmental or generalized dystonia) following DBS.
Traumatic injuries to the thumb are frequently associated with mutilation of one or more of the remaining digits. The most common digital injuries associated with thumb loss are partial or complete amputation of the index finger or index and long fingers. Occasionally, satisfactory index finger function will be preserved with damage or amputation of the middle or ring fingers, making them the best candidates for transposition. Although pollicization of the index finger has received considerable attention in the literature, pollicization of injured middle and ring finger remnants has not. Transposition of these comparatively useless digital stumps, which may be sacrificed without significant functional deficit to the rest of the hand, may be advantageously performed to create a well-functioning thumb. This procedure facilitates the conversion of a useless, mutilated hand into a well-functioning one in a single operation. We present our experience with pollicization of middle and ring finger remnants in four patients including indications, technique, and functional outcome.
