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Abstract Background Prior research has linked e-cigarette use with chronic obstructive pulmonary disease (COPD). We examined the relationship between e-cigarette use and COPD prevalence in older adults with varying cigarette use status. Methods Data from the 2020 National Health Interview Survey were used to estimate the association between each of 9 exposure categories based on cigarette use (never, former, current) and e-cigarette use (never, former, current), with respondent-reported physician-diagnosed COPD prevalence in individuals 40 years and older (N = 22,997). Weighted multivariable analysis accounted for cigarette pack years, age of cigarette smoking onset, race, income-to-poverty ratio, rurality, gender, age, and medical comorbidities. Sensitivity of results was tested in 3 separate models with addition of years since quit cigarettes, smoking intensity and duration. Results 39.7% of individuals reported ever smoking cigarettes and 10.2% reported ever using e-cigarettes. Among individuals with ever e-cigarette use, 88.5% also reported current or former cigarette smoking. The weighted prevalence of COPD was 7.2%; Among those who reported former cigarette smoking, the highest risk of COPD prevalence compared to never cigarette/never e-cigarette use was in those currently using e-cigarettes (adjusted risk ratio (ARR) 2.82, 95% confidence interval (CI) [1.5, 5.3]). The ARR for former cigarette/current e-cigarette use was significantly larger than the ARR for former cigarette/never e-cigarette use (p

Introduction Cigarette smoking and smoking-related lung disease are more common in rural (vs urban) areas of the United States (US). This study examined relationships between geographical location, cigarette risk perceptions, and current smoking among older adults who are at greatest risk of developing smoking-related lung disease. Methods The study was a secondary data analysis of 12126 respondents aged ≥40 years from Wave 5 of the Population Assessment of Tobacco and Health Study. Weighted descriptive statistics and Poisson regressions assessed current smoking (vs never or former) as a function of geographical location in a stepwise fashion, first unadjusted, then adjusting for sociodemographic characteristics, and finally for both sociodemographic characteristics and cigarette risk perceptions (4-item scale), in three separate models. Sensitivity analyses examined whether individual risk perceptions items had a greater impact on the association between geographical location and current smoking. Results Current smoking was more common among rural (20.6%) than urban (17.6%) residents. The risk ratio (RR) for rural (vs urban) residence on current smoking decreased from 1.17 (95% CI: 1.03–1.32) to 1.14 (95% CI: 1.01–1.29) to 1.08 (95% CI: 0.96–1.21) across the stepwise models. Lower cigarette risk perceptions confounded the rural-current smoking association and was an independent risk factor for smoking (adjusted RR, ARR=2.15; 95% CI: 1.94– 2.18). In sensitivity analyses, believing that cigarettes are very or extremely (vs somewhat, slightly, or not at all) harmful to health and agreeing (vs not agreeing) that secondhand smoke causes lung disease in people who do not smoke, confounded the rural-current smoking association whereas beliefs about smoking causing lung cancer or lung disease in people who smoke did not. Conclusions Lower cigarette risk perceptions among rural residents confounded the positive association between rural residence and current smoking. Results from sensitivity analyses highlight potential targets for communication campaigns aimed at promoting more accurate perceptions of the harmful health consequences of cigarette smoking.

Abstract Objective Assess the efficacy of single and multiple intra-articular injections of autologous adipose-derived stem cells (ASCs) and adipose-derived stromal vascular fraction (ADSVF) for the treatment of knee osteoarthritis (OA). Methods We conducted a thorough and systematic search of several databases, including PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, to identify relevant studies. The included studies were randomized controlled trials (RCTs) that involved single or multiple intra-articular injections of autologous ASCs or ADSVF for the treatment of patients with knee osteoarthritis, without any additional treatment, and compared to either placebo or hyaluronic acid. Results A total of seven RCTs were analyzed in this study. The results of the meta-analysis show that compared to the control group, both single and multiple intra-articular injections of ASCs or ADSVF demonstrated superior pain relief in the short term (Z = 3.10; P

This study examined associations between established cigar use and prevalence and incidence of cardiovascular diseases (CVD; congestive heart failure, stroke, or heart attack/needed bypass surgery) among U.S. adults, 40 years or older. Using Waves 1–5 (2013–2019) of the Population Assessment of Tobacco and Health (PATH) Study, incidence (Nindividuals (Nind) = 6,692; Nobservations (Nobs) = 23,738) and prevalence (Nind = 7,819; Nobs = 33,952) of CVD outcomes were examined using weighted generalized estimating equations (WGEEs) among adults who were exclusive current/former established cigar smokers (ever cigar smokers who have smoked fairly regularly), exclusive current/former established cigarette smokers (lifetime smokers of 100 or more cigarettes), dual current/former established cigarette and cigar smokers compared with never smokers of cigars or cigarettes, adjusting for covariates. The population-averaged incidence of CVD from one wave to next among exclusive current/former established cigar smokers during a six-year period based on WGEEs was low (overall average rate of 3.0 %; 95 % CI: 1.2, 7.0). Compared with never users, exclusive current/former established cigar smokers (OR = 1.67, 95 % CI: 1.11, 2.51) and exclusive current/former established cigarette smokers (OR = 2.12, 95 % CI: 1.45, 3.09) were more likely to have any CVD outcome in unadjusted analyses. When adjusted for covariates, only exclusive current/former established cigarette use was associated with CVD outcomes (AOR = 1.60, CI: 1.07, 2.40). Results suggest that exclusive established use of cigars or duration of exclusive cigar use was not associated with lifetime CVD prevalence compared with never cigar or cigarette smokers, which is important in understanding health outcomes in cigar users.

The quality of ocular fundus photographs can affect the accuracy of the morphologic assessment of the optic nerve head (ONH), either by humans or by deep learning systems (DLS). In order to automatically identify ONH photographs of optimal quality, we have developed, trained, and tested a DLS, using an international, multicentre, multi-ethnic dataset of 5015 ocular fundus photographs from 31 centres in 20 countries participating to the Brain and Optic Nerve Study with Artificial Intelligence (BONSAI). The reference standard in image quality was established by three experts who independently classified photographs as of “good”, “borderline”, or “poor” quality. The DLS was trained on 4208 fundus photographs and tested on an independent external dataset of 807 photographs, using a multi-class model, evaluated with a one-vs-rest classification strategy. In the external-testing dataset, the DLS could identify with excellent performance “good” quality photographs (AUC = 0.93 (95% CI, 0.91–0.95), accuracy = 91.4% (95% CI, 90.0–92.9%), sensitivity = 93.8% (95% CI, 92.5–95.2%), specificity = 75.9% (95% CI, 69.7–82.1%) and “poor” quality photographs (AUC = 1.00 (95% CI, 0.99–1.00), accuracy = 99.1% (95% CI, 98.6–99.6%), sensitivity = 81.5% (95% CI, 70.6–93.8%), specificity = 99.7% (95% CI, 99.6–100.0%). “Borderline” quality images were also accurately classified (AUC = 0.90 (95% CI, 0.88–0.93), accuracy = 90.6% (95% CI, 89.1–92.2%), sensitivity = 65.4% (95% CI, 56.6–72.9%), specificity = 93.4% (95% CI, 92.1–94.8%). The overall accuracy to distinguish among the three classes was 90.6% (95% CI, 89.1–92.1%), suggesting that this DLS could select optimal quality fundus photographs in patients with neuro-ophthalmic and neurological disorders affecting the ONH.

Background: Neuronal apoptosis is a major contributor to Alzheimer’s disease (AD). Periodontitis is a significant risk factor for AD. The periodontal pathogens Porphyromonas gingivalis and Treponema denticola have been shown to initiate the hallmark pathologies and behavioral symptoms of AD. Studies have found that T. denticola infection induced Tau hyperphosphorylation and amyloid β accumulation in the hippocampi of mice. Aβ accumulation is closely associated with neuronal apoptosis. However, the roles of T. denticola in neuronal apoptosis remain unclear and its roles in AD pathology need further study. Objective: This study aimed to investigate whether oral infection with T. denticola induced alveolar bone loss and neuronal apoptosis in mice. Methods: C57BL/6 mice were orally administered with T. denticola, Micro-CT was employed to assess the alveolar bone resorption. Western blotting, quantitative PCR, and TUNEL staining were utilized to detect the apoptosis-associated changes in mouse hippocampi. N2a were co-cultured with T. denticola to verify in vivo results. Results: Mice infected with T. denticola exhibited more alveolar bone loss compared with the control mice. T. denticola oral infection induced neuronal apoptosis in hippocampi of mice. Consistent results of the apoptosis-associated protein expression were observed in N2a cells treated with T. denticola and Aβ1–42 in vitro. However, the Aβ inhibitor reversed these results, suggesting that Aβ1–42 mediates T. denticola infection-induced neuronal apoptosis. Conclusions: This study found that oral infected T. denticola caused alveolar bone loss, and induced neuronal apoptosis by promoting Aβ accumulation in mice, providing evidence for the link between periodontitis and AD.

Summary: We identified a plasma signature of 11 C14 to C26 ceramides and 1 C16 dihydroceramide predictive of major adverse cardiovascular events in patients with acute myocardial infarction (AMI). Among patients undergoing coronary artery bypass surgery, those with recent AMI, compared with those without recent AMI, showed a significant increase in 5 of the signature’s 12 ceramides in plasma but not simultaneously-biopsied aortic tissue. In contrast, a rat AMI model, compared with sham control, showed a significant increase in myocardial concentrations of all 12 ceramides and up-regulation of 3 ceramide-producing enzymes, suggesting ischemic myocardium as a possible source of this ceramide signature. Key Words: acute coronary syndrome, ceramides, dihydroceramides, major adverse cardiovascular and cerebrovascular events, prognosis, risk prediction

Abstract Background High-grade serous ovarian carcinoma (HG-SOC) is the dominant tumor histologic type in epithelial ovarian cancers, exhibiting highly aberrant microRNA expression profiles and diverse pathways that collectively determine the disease aggressiveness and clinical outcomes. However, the functional relationships between microRNAs, the common pathways controlled by the microRNAs and their prognostic and therapeutic significance remain poorly understood. Methods We investigated the gene expression patterns of microRNAs in the tumors of 582 HG-SOC patients to identify prognosis signatures and pathways controlled by tumor miRNAs. We developed a variable selection and prognostic method, which performs a robust selection of small-sized subsets of the predictive features (e.g., expressed microRNAs) that collectively serves as the biomarkers of cancer risk and progression stratification system, interconnecting these features with common cancer-related pathways. Results Across different cohorts, our meta-analysis revealed two robust and unbiased miRNA-based prognostic classifiers. Each classifier reproducibly discriminates HG-SOC patients into high-confidence low-, intermediate- or high-prognostic risk subgroups with essentially different 5-year overall survival rates of 51.6-85%, 20-38.1%, and 0-10%, respectively. Significant correlations of the risk subgroup’s stratification with chemotherapy treatment response were observed. We predicted specific target genes involved in nine cancer-related and two oocyte maturation pathways (neurotrophin and progesterone-mediated oocyte maturation), where each gene can be controlled by more than one miRNA species of the distinct miRNA HG-SOC prognostic classifiers. Conclusions We identified robust and reproducible miRNA-based prognostic subsets of the of HG-SOC classifiers. The miRNAs of these classifiers could control nine oncogenic and two developmental pathways, highlighting common underlying pathologic mechanisms and perspective targets for the further development of a personalized prognosis assay(s) and the development of miRNA-interconnected pathway-centric and multi-agent therapeutic intervention.