Electronic cigarettes (e-cigarettes) may help cigarette smokers quit smoking, yet they may also facilitate cigarette smoking for never-smokers. We quantify the balance of health benefits and harms ...associated with e-cigarette use at the population level.
Monte Carlo stochastic simulation model. Model parameters were drawn from census counts, national health and tobacco use surveys, and published literature. We calculate the expected years of life gained or lost from the impact of e-cigarette use on smoking cessation among current smokers and transition to long-term cigarette smoking among never smokers for the 2014 US population cohort.
The model estimated that 2,070 additional current cigarette smoking adults aged 25-69 (95% CI: -42,900 to 46,200) would quit smoking in 2015 and remain continually abstinent from smoking for ≥7 years through the use of e-cigarettes in 2014. The model also estimated 168,000 additional never-cigarette smoking adolescents aged 12-17 and young adults aged 18-29 (95% CI: 114,000 to 229,000), would initiate cigarette smoking in 2015 and eventually become daily cigarette smokers at age 35-39 through the use of e-cigarettes in 2014. Overall, the model estimated that e-cigarette use in 2014 would lead to 1,510,000 years of life lost (95% CI: 920,000 to 2,160,000), assuming an optimistic 95% relative harm reduction of e-cigarette use compared to cigarette smoking. As the relative harm reduction decreased, the model estimated a greater number of years of life lost. For example, the model estimated-1,550,000 years of life lost (95% CI: -2,200,000 to -980,000) assuming an approximately 75% relative harm reduction and -1,600,000 years of life lost (95% CI: -2,290,000 to -1,030,000) assuming an approximately 50% relative harm reduction.
Based on the existing scientific evidence related to e-cigarettes and optimistic assumptions about the relative harm of e-cigarette use compared to cigarette smoking, e-cigarette use currently represents more population-level harm than benefit. Effective national, state, and local efforts are needed to reduce e-cigarette use among youth and young adults if e-cigarettes are to confer a net population-level benefit in the future.
Besides smoking, lung cancer can be caused by other factors, including heavy metals such as cadmium, nickel, arsenic, beryllium and hexavalent chromium Cr(VI), which is used in multiple settings, ...resulting in widespread environmental and occupational exposures as well as heavy use. The mechanism by which Cr(VI) causes lung cancer is not completely understood. Currently, it is admitted chromosome instability is a key process in the mechanism of Cr(VI)-induced cancer, and previous studies have suggested Cr(VI) impacts the lung tissue in mice by triggering tissue damage and inflammation. However, the mechanism underlying Cr(VI)-induced inflammation and its exact role in lung cancer are unclear. Therefore, this review aimed to systematically examine previous studies assessing Cr(VI)-induced inflammation and to summarize the major inflammatory pathways involved in Cr(VI)-induced inflammation. In cell culture studies, COX2, VEGF, JAK-STAT, leukotriene B4 (LTB4), MAPK, NF-ҡB and Nrf2 signaling pathways were consistently upregulated by Cr(VI), clearly demonstrating that these pathways are involved in Cr(VI)-induced inflammation. In addition, Akt signaling was also shown to contribute to Cr(VI)-induced inflammation, although discrepant findings were reported. Few mechanistic studies were performed in animal models, in which Cr(VI) upregulated oxidative pathways, NF-kB signaling and the MAPK pathway in the lung tissue. Similar to cell culture studies, opposite effects of Cr(VI) on Akt signaling were reported. This work provides insights into the mechanisms by which Cr(VI) induces lung inflammation. However, discrepant findings and other major issues in study design, both in cell and animal models, suggest that further studies are required to unveil the mechanism of Cr(VI)-induced inflammation and its role in lung cancer.
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•Cr(VI) causes lung inflammation as shown in cell culture, animal and human studies.•Cr(VI) regulates many inflammatory pathways, e.g., JAK-STAT, MAPK, NF-ҡB and Akt.•Opposite effects of Cr(VI) on Akt signaling were reported in cell and animal models.
Images are a core component of aphasia assessment and intervention that require significant resources to produce or source. Text-to-image generation is an Artificial Intelligence (AI) technology that ...has recently made significant advances and could be a source of low-cost, highly customizable images. The aim of this study was to explore the potential of AI image generation for use in aphasia by examining its efficiency and cost during generation of typical images.
Two hundred targets (80 nouns, 80 verbs, and 40 sentences) were selected at random from existing aphasia assessments and treatment software. A widely known image generator, DALL-E 2, was given text prompts for each target. The success rate, number of prompts required, and costs were summarized across target categories (noun/verb/sentence) and compared to frequency and imageability.
Of 200 targets, 189 (94.5%) successfully conveyed the key concept. The process took a mean of 2.3 min per target at a cost of $0.31 in U.S. dollars each. However, there were aesthetic flaws in many successful images that could impact their utility. Noun images were generated with the highest efficiency and accuracy, followed by verbs, while sentences were more challenging, particularly those with unusual scenes. Patterns of flaws and errors in image generation are discussed.
The ability to rapidly generate low-cost, high-quality images using AI is likely to be a major contribution to aphasia assessment and treatment going forward, particularly as advances in this technology continue.
Hexavalent chromium Cr(VI) is a known human lung carcinogen with widespread exposure in environmental and occupational settings. Despite well-known cancer risks, the molecular mechanisms of ...Cr(VI)-induced carcinogenesis are not well understood, but a major driver of Cr(VI) carcinogenesis is chromosome instability. Previously, we reported Cr(VI) induced numerical chromosome instability, premature centriole disengagement, centrosome amplification, premature centromere division, and spindle assembly checkpoint bypass. A key regulator of these events is securin, which acts by regulating the cleavage ability of separase. Thus, in this study we investigated securin disruption by Cr(VI) exposure. We exposed human lung cells to a particulate Cr(VI) compound, zinc chromate, for acute (24 h) and prolonged (120 h) time points. We found prolonged Cr(VI) exposure caused marked decrease in securin levels and function. After prolonged exposure at the highest concentration, securin protein levels were decreased to 15.3% of control cells, while securin mRNA quantification was 7.9% relative to control cells. Additionally, loss of securin function led to increased separase activity manifested as enhanced cleavage of separase substrates; separase, kendrin, and SCC1. These data show securin is targeted by prolonged Cr(VI) exposure in human lung cells. Thus, a new mechanistic model for Cr(VI)-induced carcinogenesis emerges with centrosome and centromere disruption as key components of numerical chromosome instability, a key driver in Cr(VI) carcinogenesis.
To make projections of cigarette consumption that incorporate state-specific trends in smoking behaviors, assess the potential for states to reach an ideal target, and identify State-specific targets ...for cigarette consumption.
We used 70 years (1950-2020) of annual state-specific estimates of per capita cigarette consumption (expressed as packs per capita or "ppc") from the Tax Burden on Tobacco reports (N = 3550). We summarized trends within each state by linear regression models and the variation in rates across states by the Gini coefficient. Autoregressive Integrated Moving Average (ARIMA) models were used to make state-specific forecasts of ppc from 2021 through 2035.
Since 1980, the average rate of decline in US per capita cigarette consumption was 3.3% per year, but rates of decline varied considerably across US states (SD = 1.1% per year). The Gini coefficient showed growing inequity in cigarette consumption across US states. After reaching its lowest level in 1984 (Gini = 0.09), the Gini coefficient began increasing by 2.8% (95% CI: 2.5%, 3.1%) per year from 1985 to 2020 and is projected to continue to increase by 48.1% (95% PI = 35.3%, 64.2%) from 2020 to 2035 (Gini = 0.35; 95% PI: 0.32, 0.39). Forecasts from ARIMA models suggested that only 12 states have a realistic chance (≥50%) of reaching very low levels of per capita cigarette consumption (≤13 ppc) by 2035, but that all US states have opportunity to make some progress.
While ideal targets may be out of reach for most US states within the next decade, every US state has the potential to lower its per capita cigarette consumption, and our identification of more realistic targets may provide a helpful incentive.
A key hypothesis for how hexavalent chromium Cr(VI) causes cancer is that it drives chromosome instability (CIN), which leads to neoplastic transformation. Studies show chronic Cr(VI) can affect DNA ...repair and induce centrosome amplification, which can lead to structural and numerical CIN. However, no studies have considered whether these outcomes are transient or permanent. In this study, we exposed human lung cells to particulate Cr(VI) for three sequential 24-hour periods, each separated by about a month. After each treatment, cells were seeded at colony-forming density, cloned, expanded, and retreated, creating three generations of clonal cell lines. Each generation of clones was tested for chromium sensitivity, chromosome complement, DNA repair capacity, centrosome amplification, and the ability to grow in soft agar. After the first treatment, Cr(VI)-treated clones exhibited a normal chromosome complement, but some clones showed a repair-deficient phenotype and amplified centrosomes. After the second exposure, more than half of the treated clones acquired an abnormal karyotype including numerical and structural alterations, with many exhibiting deficient DNA double-strand break repair and amplified centrosomes. The third treatment produced new abnormal clones, with previously abnormal clones acquiring additional abnormalities and most clones exhibiting repair deficiency. CIN, repair deficiency, and amplified centrosomes were all permanent and heritable phenotypes of repeated Cr(VI) exposure. These outcomes support the hypothesis that CIN is a key mechanism of Cr(VI)-induced carcinogenesis.
Chromium, a major public health concern and human lung carcinogen, causes fundamental changes in chromosomes and DNA repair in human lung cells.
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Hexavalent chromium Cr(VI) is a well-known and widespread environmental contaminant associated with a variety of adverse health effects, in particular lung cancer. The primary route of exposure in ...humans is through inhalation. Particulate forms of Cr(VI) are the most potent but in vivo studies are difficult. Intratracheal instillation requires highly trained surgical procedures which also limits the number of repeated exposures possible and thus requires high doses. Inhalation studies can deliver lower more chronic doses but are expensive and generate dangerous aerosols. We evaluated an oropharyngeal aspiration exposure route for zinc chromate particles in Wistar rats. Animals were treated once per week for 90 days. We found chromium accumulated in the lungs, blood, and reproductive tissues of all treated animals. Additionally, we found inflammatory indicators in the lung were elevated and circulating lymphocytes had increased chromosomal damage. These results show oropharyngeal aspiration provides a practicable exposure route for chronic and sub-chronic exposures of Cr(VI) particles.
•Oropharyngeal aspiration of zinc chromate particles leads to increased chromium levels in multiple tissues.•Sub-chronic exposure of zinc chromate particles in rats increased macrophage infiltration in the lungs.•Sub-chronic exposure of zinc chromate particles in rats increased chromosome instability in lymphocytes.
Aphasia is a debilitating chronic acquired language disorder that impacts heavily on a person's life. Behavioural treatments aim to remediate language processing skills or to enhance communication ...between the person with aphasia and others, and a number of different treatments are efficacious. However, it is unclear how much of a particular treatment a person needs in order to optimise recovery of language and communication skills following stroke.
Systematic search for and meta-analysis of experimental studies that directly compared different amounts of the same behavioural aphasia treatment, following PRISMA guidelines.
Treatment dose research in aphasia is an emerging area. Just six studies comparing different doses of the same intervention met all criteria for inclusion. Evidence from these studies was synthesised and meta-analysed, where possible. Meta-analyses were inconclusive due to limited data; however, there are indications that suggest increased dose may confer greater improvement on language and communication measures, but with diminishing returns over time. Aphasia severity and chronicity may affect dose-response relationships.
There is currently insufficient evidence to determine the effect of dose on treatment response. A dedicated and coordinated research agenda is required to systematically explore dose-response relationships in post-stroke aphasia interventions.
A video abstract is available in the
Supplementary Material
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Implications for rehabilitation
The investigation of the effect of dose on treatment outcomes in post-stroke aphasia is an emerging research area with few studies reporting comparison of different amounts of the same intervention.
In the acute phase of recovery following stroke, higher doses of treatment provided over short periods may not be preferable, tolerable, or superior to lower doses of the same treatment.
In the chronic phase, providing additional blocks of treatment may confer additional benefit for some people with aphasia but with diminishing returns.
People with chronic aphasia can achieve and maintain significant gains in picture naming after a relatively brief period of high-dose treatment.
OBJECTIVE Meningiomas are the most common primary tumor of the central nervous system. Complete resection can be curative, but intraoperative identification of dural tails and tumor remnants poses a ...clinical challenge. Given data from preclinical studies and previous clinical trials, the authors propose a novel method of localizing tumor tissue and identifying residual disease at the margins via preoperative systemic injection of a near-infrared (NIR) fluorescent contrast dye. This technique, what the authors call "second-window indocyanine green" (ICG), relies on the visualization of ICG approximately 24 hours after intravenous injection. METHODS Eighteen patients were prospectively identified and received 5 mg/kg of second-window ICG the day prior to surgery. An NIR camera was used to localize the tumor prior to resection and to inspect the margins following standard resection. The signal to background ratio (SBR) of the tumor to the normal brain parenchyma was measured in triplicate. Gross tumor and margin specimens were qualitatively reported with respect to fluorescence. Neuropathological diagnosis served as the reference gold standard to calculate the sensitivity and specificity of the imaging technique. RESULTS Eighteen patients harbored 15 WHO Grade I and 3 WHO Grade II meningiomas. Near-infrared visualization during surgery ranged from 18 to 28 hours (mean 23 hours) following second-window ICG infusion. Fourteen of the 18 tumors demonstrated a markedly elevated SBR of 5.6 ± 1.7 as compared with adjacent brain parenchyma. Four of the 18 patients showed an inverse pattern of NIR signal, that is, stronger in the adjacent normal brain than in the tumor (SBR 0.31 ± 0.1). The best predictor of inversion was time from injection, as the patients who were imaged earlier were more likely to demonstrate an appropriate SBR. The second-window ICG technique demonstrated a sensitivity of 96.4%, specificity of 38.9%, positive predictive value of 71.1%, and a negative predictive value of 87.5% for tumor. CONCLUSIONS Systemic injection of NIR second-window ICG the day before surgery can be used to visualize meningiomas intraoperatively. Intraoperative NIR imaging provides higher sensitivity in identifying meningiomas than the unassisted eye. In this study, 14 of the 18 patients with meningioma demonstrated a strong SBR compared with adjacent brain. In the future, reducing the time interval from dye injection to intraoperative imaging may improve fluorescence at the margins, though this approach requires further investigation. Clinical trial registration no.: NCT02280954 ( clincialtrials.gov ).
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