Combined effects of smoking and alcohol consumption on the risk of liver cancer according to metabolic syndrome: A nested case-control study in South Korea.

Tobacco and alcohol may interact to increase the risk of liver cancer, which might be modified by other risk factors. Their combined effects in the context of metabolic syndrome (MetS) remain unclear. Given the increasing prevalence of MetS, this nested case-control study was conducted to evaluate the combined effects of smoking and alcohol consumption on liver cancer risk with stratification by MetS. We included 15,352 liver cancer patients and 92,112 matched controls who attended the nationwide general health examination during 2009-2019, using a customized database (N = 5,545,835) from the Korean National Health Insurance Service. Liver cancer risk according to smoking and alcohol consumption was estimated using conditional multivariable logistic regression. Additive and multiplicative interactions between these two factors were assessed. Results showed that in men, dual current users were at a significantly higher risk of liver cancer compared with dual nonusers, adjusted odds ratio (aOR) = 1.61, 95% confidence interval: (1.50, 1.72). Interactions were detected between light-to-moderate alcohol consumption (0.1-28 g/day) and heavy smoking (>20 pack-years) on additive scale, relative excess risk due to interaction = 0.34 (0.16, 0.51), attributable proportion = 0.22 (0.11, 0.33), synergy index = 2.75 (1.85, 3.66), and multiplicative scale, aOR for the product term = 1.28 (1.11, 1.49). An additive interaction was also revealed between light-to-moderate drinking and light-to-moderate smoking in the MetS subgroup. In women, light-to-moderate drinking/nonsmoking was negatively associated with the risk in the non-MetS subgroup. In conclusion, a holistic health promotion program should target male dual users of tobacco cigarettes and alcohol, including light-to-moderate users, especially those with MetS.

Suicide mortality following the implementation of tobacco packaging and pricing policies in Korea: an interrupted time-series analysis.

BACKGROUND: To prevent tobacco use in Korea, the national quitline number was added to tobacco packages in December 2012, tobacco prices were raised by 80% in January 2015, and graphic health warning labels were placed on tobacco packages in December 2016. This study evaluated the association of these tobacco packaging and pricing policies with suicide mortality in Korea. METHODS: Monthly mortality from suicide was obtained from Cause-of-Death Statistics in Korea from December 2007 to December 2019. Interrupted time-series analysis was performed using segmented Poisson regression models. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated adjusted for suicide prevention strategies. RESULTS: Suicide mortality was 20 per 1,000,000 in December 2007 and showed a downward trend over the study period. After the implementation of tobacco packaging and pricing policies, suicide mortality immediately declined by - 0.09 percent points (95% CI = - 0.19 to 0.01; P > 0.05) for the national quitline number, - 0.22 percent points (95% CI = - 0.35 to - 0.09; P < 0.01) for tobacco prices, and - 0.30 percent points (95% CI = - 0.49 to - 0.11; P < 0.01) for graphic health warning labels. The corresponding RRs for these post-implementation changes compared with the pre-implementation level were 0.91 (95% CI = 0.83 to 1.00), 0.80 (95% CI = 0.70 to 0.91), and 0.74 (95% CI = 0.61 to 0.90), respectively. Significant associations between tobacco control policies and suicide mortality were observed even when stratified by sex and region. CONCLUSIONS: The findings of this study provide new evidence for an association between tobacco control policies and deaths by suicide. An array of effective tobacco control policies should be considered for prevention programs targeting suicide.

Molecular mapping of the broad bean wilt virus 2 resistance locus bwvr in Capsicum annuum using BSR-seq.

KEY MESSAGE: Bulked segregant RNA seq of pools of pepper accessions that are susceptible or resistant to Broad bean wilt virus 2 identifies a gene that might confer resistance to this devastating pathogen. The single-stranded positive-sense RNA virus Broad bean wilt virus 2 (BBWV2) causes substantial damage to pepper (Capsicum annuum) cultivation. Here, we describe mapping the BBWV2 resistance locus bwvr using a F7:8 recombinant inbred line (RIL) population constructed by crossing the BBWV2-resistant pepper accession 'SNU-C' with the susceptible pepper accession 'ECW30R.' All F1 plants infected with the BBWV2 strain PAP1 were susceptible to the virus, and the RIL population showed a 1:1 ratio of resistance to susceptibility, indicating that this trait is controlled by a single recessive gene. To map bwvr, we performed bulked segregant RNA-seq (BSR-seq). We sequenced pools of resistant and susceptible lines from the RILs and aligned the reads to the high-quality 'Dempsey' reference genome to identify variants between the pools. This analysis identified 519,887 variants and selected the region from 245.9-250.8 Mb of the Dempsey reference genome as the quantitative trait locus region for bwvr. To finely map bwvr, we used newly designed high-resolution melting (HRM) and Kompetitive allele specific PCR (KASP) markers based on variants obtained from the BSR-seq reads and the PepperSNP16K array. Comparative analysis identified 11 SNU-C-specific SNPs within the bwvr locus. Using markers derived from these variants, we mapped the candidate bwvr locus to the region from 246.833-246.949 kb. SNU-C-specific variants clustered near DEM.v1.00035533 within the bwvr locus. DEM.v1.00035533 encodes the nitrate transporter NPF1.2 and contains a SNP within its 5' untranslated region. The bwvr locus, which contains four genes including DEM.v1.00035533, could represent a valuable resource for global pepper breeding programs.

Predictors of Late Adverse Events in Patients with Surgically Treated Type I Aortic Dissection.

OBJECTIVE: Residual aortic dissection (AD) following DeBakey type I AD repair is associated with a high rate of adverse events that need additional intervention or surgery. This study aimed to identify clinical and early post-operative computed tomography (CT) imaging factors associated with adverse events in patients with type I AD after ascending aorta replacement. METHODS: This single centre, retrospective cohort study included consecutive patients with type I AD who underwent ascending aorta replacement from January 2011 to December 2017 and post-operative CT within three months. The primary outcome was AD related adverse events, defined as AD related death and re-operation due to aortic aneurysm or impending rupture. The location and size of the primary intimal tears, aortic diameter, and false lumen status were evaluated. Regression analyses were performed to identify factors associated with AD related adverse events. A decision tree model was used to classify patients as high or low risk. RESULTS: Of 103 participants (55.43 ± 13.94 years; 49.5% male), 24 (23.3%) experienced AD related adverse events. In multivariable Cox regression analysis, connective tissue disease (hazard ratio [HR] 15.33; p < .001), maximum aortic diameter ≥ 40 mm (HR 4.90; p < .001), and multiple (three or more) intimal tears (HR 7.12; p < .001) were associated with AD related adverse events. The three year cumulative survival free from AD related events was lower in the high risk group with aortic diameter ≥ 40 mm and multiple intimal tears (41.7% vs. 90.9%; p < .001). CONCLUSION: Early post-operative CT findings indicating a maximum aortic diameter ≥ 40 mm and multiple intimal tears may predict a higher risk of adverse events. These findings suggest the need for careful monitoring and more vigilant management approaches in these cases.

Prophylactic effect of pilocarpine on acute sialadenitis following radioactive iodine therapy in thyroid cancer patients.

Purpose: Our aim was to evaluate the effect of prophylactic pilocarpine on acute salivary symptoms after radioactive iodine (RAI) therapy in patients with differentiated thyroid cancer. Methods: We enrolled 88 patients (76 women and 12 men; mean age: 47 years; range: 20-74 years) with differentiated thyroid cancer who received RAI. Patients were divided into pilocarpine (51 patients) and control (37 patients) groups. Pilocarpine was given orally, at a dose of 5 mg three times a day, from 2 days before and 12 days after RAI therapy. Symptoms and signs of acute sialadenitis within 3 months of RAI therapy were recorded. Results: During the 3 months after RAI therapy, 13 of the 88 patients (14.7%) developed acute symptomatic sialadenitis (swelling or pain of salivary glands). Acute salivary symptoms were reported by 4 (7.8%) and 9 (24.3%) patients in the pilocarpine and control groups, respectively. Acute salivary symptoms were less frequent in the pilocarpine than control group (p = 0.04), but did not differ by age, sex, or RAI dose (p = 0.3357, p = 0.428, and p = 0.2792). Conclusions: Pilocarpine reduced the likelihood of acute sialadenitis after RAI therapy in patients with differentiated thyroid cancer.

Association between current cigarette prices and cessation behaviors among male adult smokers: findings from 2018 to 2020 ITC Vietnam surveys.

BACKGROUND: This study evaluated the impact of the tax increase in January 2019 on changes in intention to quit and the effect of cigarette prices on quit attempts and successful quitting among male cigarette smokers in Vietnam. METHODS: Data were derived from the ITC project in Vietnam, which included 1585 adult smokers at baseline (Wave 1, Aug-Oct 2018) followed up to waves 2 (Sep-Nov 2019) and 3 (Sep-Dec 2020). Generalized estimating equations regression was performed to estimate changes in the intention to quit. Multiple logistic regression analysis was used to evaluate the cigarette price of a cigarette pack in relation to quit attempts and successful quitting. RESULTS: The increase in cigarette tax in 2019 did not significantly increase the likelihood of the intention to quit. After the tax increase, 63.6% of participants who smoked made a quit attempt, and 27.6% successfully quit smoking in the follow-up waves. However, the price of a cigarette pack was not significantly associated with quit attempts and successful quitting. The study did not observe a significant impact of cigarette prices on quit attempts and successful quitting in all subgroups of household income. Factors associated with quit attempts included the number of cigarettes smoked and the intention to quit, while those associated with successful quitting included age, dual use of cigarettes and other tobacco products, and the intention to quit. CONCLUSION: Current cigarette prices were not associated with cessation behaviors even within the lowest household income group. Therefore, a sharp rise in cigarette tax is required to incentivize smokers to quit smoking.

Classification of IDH wild-type glioblastoma tumorspheres into low- and high-invasion groups based on their transcriptional program.

BACKGROUND: Glioblastoma (GBM), one of the most lethal tumors, exhibits a highly infiltrative phenotype. Here, we identified transcription factors (TFs) that collectively modulate invasion-related genes in GBM. METHODS: The invasiveness of tumorspheres (TSs) were quantified using collagen-based 3D invasion assays. TF activities were quantified by enrichment analysis using GBM transcriptome, and confirmed by cell-magnified analysis of proteome imaging. Invasion-associated TFs were knocked down using siRNA or shRNA, and TSs were orthotopically implanted into mice. RESULTS: After classifying 23 patient-derived GBM TSs into low- and high-invasion groups, we identified active TFs in each group-PCBP1 for low invasion, and STAT3 and SRF for high invasion. Knockdown of these TFs reversed the phenotype and invasion-associated-marker expression of GBM TSs. Notably, MRI revealed consistent patterns of invasiveness between TSs and the originating tumors, with an association between high invasiveness and poor prognosis. Compared to controls, mice implanted with STAT3- or SRF-downregulated GBM TSs showed reduced normal tissue infiltration and tumor growth, and prolonged survival, indicating a therapeutic response. CONCLUSIONS: Our integrative transcriptome analysis revealed three invasion-associated TFs in GBM. Based on the relationship among the transcriptional program, invasive phenotype, and prognosis, we suggest these TFs as potential targets for GBM therapy.

Exposure to Electronic Cigarette Advertisements and Use of Electronic Cigarettes: A Meta-analysis of Prospective Studies.

INTRODUCTION: Electronic cigarette (EC) advertisements remain unregulated and approach consumers in TV commercials, print ads, radio, and other forms of digital marketing. AIMS AND METHODS: This study aimed to assess whether exposure to EC advertisements is associated with the use of EC by using a meta-analysis of prospective studies. We searched PubMed, EMBASE, and Web of Science to locate eligible studies in November 2021. Pooled adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated using a random-effects meta-analysis. RESULTS: Out of 1635 articles searched from databases, we included seven prospective studies that met inclusion criteria in the final analysis. Four out of seven studies involved participants under 18 years of age. In the meta-analysis of all studies, exposure to EC advertisements was significantly associated with the increased use of ECs (aOR = 1.53, 95% CI 1.22 to 1.92; I2 = 60.1%). In the subgroup meta-analyses by source of advertisements, there was no significant association between exposure to EC advertisements on TV, radio, or billboards and the use of EC, while exposure to EC advertisements in retail stores and on Internet or social media significantly increased the use of EC. CONCLUSIONS: Exposure to EC advertisements was associated with the increased use of ECs, specifically in retail stores and on Internet or social media among adolescents and young adults. Because EC use could serve as a gateway to cigarette smoking in adolescents and young adults, more strict regulations and restrictions on EC advertisements are needed. IMPLICATIONS: Concurrent with the rise in electronic cigarette (EC) sales, advertising expenditures for ECs have been increased in the past decade, and there is controversy over the association between exposure to EC advertisements and the use of ECs. This meta-analysis of seven prospective studies showed that exposure to EC advertisements was significantly associated with the increased use of ECs, specifically in retail stores and on Internet or social media among adolescents and young adults. Because, EC use could serve as a gateway to cigarette smoking in adolescents and young adults, more strict regulations and restrictions on EC advertisements are needed.

Role of geographic characteristics in the spatial cluster detection of cancer: Evidence in South Korea, 1999-2013.

BACKGROUND: Identification of high-risk areas of cancer, referred to as spatial clusters, can inform targeted policies for cancer control. Although cancer cluster detection could be affected by various geographic characteristics including sociodemographic and environmental factors which impacts could also vary over time, studies accounting for such influence remain limited. This study aims to assess the role of geographic characteristics in the spatial cluster detection for lung and stomach cancer over an extended period. METHODS: We obtained sex-specific age-standardized incidence and mortality rates of lung and stomach cancer as well as geographic characteristics across 233 districts in South Korea for three five-year periods between 1999 and 2013. We classified geographic characteristics of each district into four categories: demography, socioeconomic status, behaviors, and physical environments. Specifically, we quantified physical environments using measures of greenness, concentrations of particulate matter and nitrogen dioxide, and air pollution emissions. Finally, we conducted cluster detection analyses using weighted normal spatial scan statistics with the residuals from multiple regression analyses performed with the four progressive sets of geographic attributes. RESULTS: We found that the size of clusters reduced as we progressively adjusted for geographic covariates. Among the four categories, physical environments had the greatest impact on the reduction or disappearance of clusters particularly for lung cancer consistently over time. Whereas older population affected a decrease of lung cancer clusters in the early period, the contribution of education was large in the recent period. The impact was less clear in stomach cancer than lung cancer. CONCLUSION: Our findings highlight the importance of geographic characteristics in explaining the existing cancer clusters and identifying new clusters, which jointly provides practical guidance to cancer control.

Cancer Risk According to Alcohol Consumption Trajectories: A Population-based Cohort Study of 2.8 Million Korean Men.

BACKGROUND: Alcohol drinking behaviors change temporally and can lead to changes in related cancer risks; previous studies have been unable to identify the association between the two using a single-measurement approach. Thus, this study aimed to investigate the association of drinking trajectories with the cancer risk in Korean men. METHODS: A trajectory analysis using group-based trajectory modeling was performed on 2,839,332 men using data on alcohol drinking levels collected thrice during the Korean National Health Insurance Service's general health screening program conducted between 2002 and 2007. Cox proportional hazards regression was performed to evaluate the associations between drinking trajectories and cancer incidence, after adjustments for age, income, body mass index, smoking status, physical activity, family history of cancer, and comorbidities. RESULTS: During 10.5 years of follow-up, 189,617 cancer cases were recorded. Six trajectories were determined: non-drinking, light, moderate, decreasing-heavy, increasing-heavy, and steady-heavy. Light-to-heavy alcohol consumption increased the risk for all cancers combined in a dose-dependent manner (adjusted hazard ratio [aHR] 1.03; 95% confidence interval [CI], 1.02-1.05 for light drinking, aHR 1.06; 95% CI 1.05-1.08 for moderate drinking, aHR 1.19; 95% CI, 1.16-1.22 for decreasing-heavy drinking, aHR 1.23; 95% CI, 1.20-1.26 for increasing-heavy drinking, and aHR 1.33; 95% CI, 1.29-1.38 for steady-heavy drinking [P-trend <0.001]). Light-to-heavy alcohol consumption was linked to lip, oral cavity, pharyngeal, esophageal, colorectal, laryngeal, stomach, and gallbladder and biliary tract cancer risks, while heavy alcohol consumption was associated with hepatic, pancreatic, and lung cancer risks. An inverse association was observed for thyroid cancer. The cancer risks were lower for decreasing-heavy drinkers, compared to steady-heavy drinkers. CONCLUSION: No safe drinking limits were identified for cancer risks; reduction in heavy intake had protective effects.

Effect of Tulobuterol Patch Versus Placebo on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomies: A Randomized Controlled Trial.

BACKGROUND: Perioperative respiratory adverse events are common in children. We aimed to evaluate the effect of the transdermal ß-2 agonist, tulobuterol, compared with that of placebo on the incidence of perioperative respiratory adverse events in pediatric patients undergoing tonsillectomy. METHODS: In this triple-blinded (patient, anesthesia provider, and outcome assessor) randomized controlled trial, 188 patients were randomly allocated to receive tulobuterol or a placebo. The tulobuterol groups received a tulobuterol patch (1 mg) masked with a bandage, whereas the placebo only received the bandage. The assigned bandage was applied to the patients 8 to 10 hours before the surgery. The primary outcome was the occurrence of any perioperative respiratory adverse events: oxygen desaturation <95%, airway obstruction, laryngospasm, bronchospasm, severe coughing, or stridor. The outcomes were evaluated using the average relative effect test, which estimates the effect of individual components of a composite outcome and then averages effects across components. RESULTS: A total of 88 and 94 patients who received tulobuterol and placebo, respectively, were analyzed. The incidence of any perioperative respiratory adverse event was lower with tulobuterol (n = 13/88; 14.7%) than that with the placebo (n = 40/94; 42.5%), with an estimated average relative risk (95% confidence interval) across components of 0.35 (0.20-0.60; P < .001). The symptoms of airway obstruction were lower with tulobuterol (n = 8/88; 9.0%) than that with the placebo (n = 32/94; 34.0%), with relative risk (95% CI) of 0.31 (0.17-0.56; P < .001). The occurrence of severe coughing was lower with tulobuterol (n = 1/88; 1.1%) than that with the placebo (n = 8/94; 8.5%), with relative risk (95% CI) of 0.15 (0.03-0.68; P = .014). CONCLUSIONS: In preschool children undergoing tonsillectomy, the preoperative application of a tulobuterol patch could decrease the occurrence of perioperative respiratory adverse events. Further studies are needed to elucidate the effect of the tulobuterol patch in a broad spectrum of pediatric anesthesia.

Effect of preoperative patient education and simulated mouth breathing training on opioid requirements in the post-anesthesia care unit after nasal surgery: a randomized controlled study.

BACKGROUND: A simulated education, prior to surgery about postoperative nasal stuffiness and ease of breathing through the mouth may help patients tolerate discomfort after nasal surgery. This study aimed to investigate the effect of preoperative simulated education on immediate postoperative opioid requirements in patients undergoing elective nasal surgery. METHODS: This randomized controlled trial of 110 patients undergoing nasal surgery randomly allocated patients into either a control (group C) or an education group (group E). One day before surgery, patients in group E were intensively trained to breathe through the mouth by using a nasal clip, with informative explanations about inevitable nasal obstruction and discomfort following surgery. Patients in group C were provided with routine preoperative information. Total intravenous anesthesia (TIVA) with propofol and remifentanil was used for anesthesia. No further opioid was used for analgesia intraoperatively. The primary outcome was index opioid (fentanyl) requirements at the post-anesthesia recovery unit (PACU). Secondary outcomes were emergence agitation, pain scores at the PACU, and postoperative recovery using the Quality of Recovery-15 (QoR15-K). RESULTS: The rate of opioid use in the PACU was 51.0% in the group E and 39.6% in the group C (p = 0.242). Additional request for analgesics other than index opioid was not different between the groups. Emergence agitation, postoperative pain severity, and QoR15-K scores were comparable between the groups. CONCLUSION: Preoperative education with simulated mouth breathing in patients undergoing nasal surgery did not reduce opioid requirements. TRIAL REGISTRATION: KCT0006264; 16/09/2021; Clinical Research Information Services ( https://cris.nih.go.kr ).

Anti-Periodontitis Effects of Dendropanax morbiferus H.Lév Leaf Extract on Ligature-Induced Periodontitis in Rats.

Periodontitis is caused by pathogens in the oral cavity. It is a chronic infectious disease that causes symptoms including gingival bleeding and tooth loss resulting from the destruction of periodontal tissues coupled with inflammation. Dendropanax morbiferus H.Lév (DM) is a natural product that exhibits various biological activities with few side effects. In this study, the potential of DM leaf hot-water extracts (DMWE) as a treatment for periodontitis was determined and its anti-oxidant and anti-inflammatory effects were evaluated. Compounds in DMWE were identified by high-performance liquid chromatography (HPLC) and nitric oxide (NO) and prostaglandin E2 (PGE2) production was measured in RAW 264.7 cells. We measured the gingival index and gingival sulcus depth, and micro-CT was performed in vivo using a ligature-induced periodontitis rat model, which is similar to human periodontitis. The DMWE-treated group exhibited a decrease in cytokine concentration and relieved the gingival index and gingival sulcus depth compared with the periodontitis-induced control group. In addition, micro-CT and histological analysis revealed that DMWE exhibited anti-inflammatory effects and improved alveolar bone loss in periodontitis-induced rats. These findings suggest that DMWE has excellent anti-oxidant and anti-inflammatory effects that protect and prevent periodontal tissue damage and tooth loss caused by the inflammatory response.

Etomoxir, a carnitine palmitoyltransferase 1 inhibitor, combined with temozolomide reduces stemness and invasiveness in patient-derived glioblastoma tumorspheres.

INTRODUCTION: The importance of fatty acid oxidation (FAO) in the bioenergetics of glioblastoma (GBM) is being realized. Etomoxir (ETO), a carnitine palmitoyltransferase 1 (CPT1) inhibitor exerts cytotoxic effects in GBM, which involve interrupting the FAO pathway. We hypothesized that FAO inhibition could affect the outcomes of current standard temozolomide (TMZ) chemotherapy against GBM. METHODS: The FAO-related gene expression was compared between GBM and the tumor-free cortex. Using four different GBM tumorspheres (TSs), the effects of ETO and/or TMZ was analyzed on cell viability, tricarboxylate (TCA) cycle intermediates and adenosine triphosphate (ATP) production to assess metabolic changes. Alterations in tumor stemness, invasiveness, and associated transcriptional changes were also measured. Mouse orthotopic xenograft model was used to elucidate the combinatory effect of TMZ and ETO. RESULTS: GBM tissues exhibited overexpression of FAO-related genes, especially CPT1A, compared to the tumor-free cortex. The combined use of ETO and TMZ further inhibited TCA cycle and ATP production than single uses. This combination treatment showed superior suppression effects compared to treatment with individual agents on the viability, stemness, and invasiveness of GBM TSs, as well as better downregulation of FAO-related gene expression. The results of in vivo study showed prolonged survival outcomes in the combination treatment group. CONCLUSION: ETO, an FAO inhibitor, causes a lethal energy reduction in the GBM TSs. When used in combination with TMZ, ETO effectively reduces GBM cell stemness and invasiveness and further improves survival. These results suggest a potential novel treatment option for GBM.

A novel biguanide (IM1761065) inhibits bioenergetics of glioblastoma tumorspheres.

PURPOSE: Glioblastoma (GBM) is a rapidly growing tumor in the central nervous system with altered metabolism. Depleting the bioenergetics of tumors with biguanides have been suggested as an effective therapeutic approach for treating GBMs. The purpose of this study was to determine the effects of IM1761065, a novel biguanide with improved pharmacokinetics, on GBM-tumorspheres (TSs). METHODS: The biological activities of IM1761065 on GBM-TSs, including their effects on viability, ATP levels, cell cycle, stemness, invasive properties, and transcriptomes were examined. The in vivo efficacy of IM1761065 was tested in a mouse orthotopic xenograft model. RESULTS: IM1761065 decreased the viability and ATP levels of GBM-TSs in a dose-dependent manner, and reduced basal and spare respiratory capacity in patient-derived GBM-TS, as measured by the oxygen consumption rate. Sphere formation, expression of stemness-related proteins, and invasive capacity of GBM-TSs were also significantly suppressed by IM1761065. A gene-ontology comparison of IM1761065-treated groups showed that the expression levels of stemness-related, epithelial mesenchymal transition-related, and mitochondrial complex I genes were also significantly downregulated by IM1761065. An orthotopic xenograft mouse model showed decreased bioluminescence in IM1761065-treated cell-injected mice at 5 weeks. IM1761065-treated group showed longer survival than the control group (P = 0.0289, log-rank test). CONCLUSION: IM1761065 is a potent inhibitor of oxidative phosphorylation. The inhibitory effect of IM1761065 on the bioenergetics of GBM-TS suggests that this novel compound could be used as a new drug for the treatment of GBM.

Dual inhibition of CPT1A and G6PD suppresses glioblastoma tumorspheres.

PURPOSE: Limited treatment options are currently available for glioblastoma (GBM), an extremely lethal type of brain cancer. For a variety of tumor types, bioenergetic deprivation through inhibition of cancer-specific metabolic pathways has proven to be an effective therapeutic strategy. Here, we evaluated the therapeutic effects and underlying mechanisms of dual inhibition of carnitine palmitoyltransferase 1A (CPT1A) and glucose-6-phosphate dehydrogenase (G6PD) critical for fatty acid oxidation (FAO) and the pentose phosphate pathway (PPP), respectively, against GBM tumorspheres (TSs). METHODS: Therapeutic efficacy against GBM TSs was determined by assessing cell viability, neurosphere formation, and 3D invasion. Liquid chromatography-mass spectrometry (LC-MS) and RNA sequencing were employed for metabolite and gene expression profiling, respectively. Anticancer efficacy in vivo was examined using an orthotopic xenograft model. RESULTS: CPT1A and G6PD were highly expressed in GBM tumor tissues. Notably, siRNA-mediated knockdown of both genes led to reduced viability, ATP levels, and expression of genes associated with stemness and invasiveness. Similar results were obtained upon combined treatment with etomoxir and dehydroepiandrosterone (DHEA). Transcriptome analyses further confirmed these results. Data from LC-MS analysis showed that this treatment regimen induced a considerable reduction in the levels of metabolites associated with the TCA cycle and PPP. Additionally, the combination of etomoxir and DHEA inhibited tumor growth and extended survival in orthotopic xenograft model mice. CONCLUSION: Our collective findings support the utility of dual suppression of CPT1A and G6PD with selective inhibitors, etomoxir and DHEA, as an efficacious therapeutic approach for GBM.

Perceptions of Heated Tobacco Products (HTPs) and Intention to Quit Among Adult Tobacco Users in Korea.

BACKGROUND: The popularity of heated tobacco products (HTPs) has been growing globally but, limited information exists on tobacco use behaviors and its impact on tobacco control. This study investigates awareness and perception of HTPs among tobacco users and whether perceptions of HTPs are associated with HTP use and intention to quit. METHODS: We invited 2,000 tobacco users aged 19-65 years with countrywide representation to an online survey in November 2018. Information on general characteristics, tobacco use behaviors, awareness and perception of HTPs, and intention to quit were gathered. Multinomial logistic regression analysis and ANCOVA were used for estimation of association and comparison. RESULTS: Among all tobacco users, 36.8% were classified as ever users, whereas 28.3% had used HTPs in the past 30 days, which was higher than expected. Users of liquid-based e-cigarettes (odds ratio [OR] 1.578; 95% confidence interval [CI], 1.210-2.056) and poly-product users (OR 2.029; 95% CI, 1.121-3.671) showed higher intention to quit within 1 month when compared to users of conventional cigarettes (CCs), whereas HTP users and dual product users did not. HTP users rated HTPs more favorably than CCs in terms of smoke, smell, harm, aid in quitting, design, and price than users of other products did (P-value < 0.001). CONCLUSION: We find that positive perception of HTPs following strategic marketing from tobacco companies could have contributed to a greater increase in HTP use than expected in Korea. However, HTPs might not be considered substitutes for CCs for quitting tobacco use because a significant proportion of dual product users reported a lower intention to quit.

Bringing Assessment-to-Instruction (A2i) Technology to Scale: Exploring the Process from Development to Implementation.

Bringing effective, research-based literacy interventions into the classroom is challenging, especially given the cultural and linguistic diversity of today's classrooms. We examined the promise of Assessment-to-Instruction (A2i) technology redesigned to be used at scale to support teachers' implementation of the individualized student instruction (ISI) intervention from kindergarten through third grade. In seven randomized controlled trials, A2i and ISI have demonstrated efficacy. However, the research version of A2i was not scalable. In order to bring A2i to scale in schools serving linguistically diverse students, we carried out the current study across two phases. This study represents both an exploration of what it takes to bring an educational intervention to scale (Phase 1) and a quasi-experiment on the literacy outcomes of learners whose teachers used the technology (Phase 2). We integrated assessments of vocabulary, word decoding, and reading comprehension; revised the A2i algorithms to account for the constellation of skills English learners (ELs) bring to the classroom; updated the user interfaces and added new graphic features; and improved bandwidth and stability of the technology. Findings were mixed, including several non-significant results, a marginally significant intent-to-treat effect on word reading in kindergarten and first grade for English monolingual students and ELs, and one significant interaction effect, which suggested ELs and students with less developed reading skills in second and third grade benefitted most from the intervention. With some caution, we conclude that A2i demonstrates potential to be used at scale and promise of effectiveness for improving code-focused skills for diverse learners.

The relationship among home language use, parental beliefs, and Spanish-speaking children's vocabulary.

This study investigated the relationship among home language use, parents' beliefs about dual language development, and Spanish-speaking children's vocabulary knowledge. Parents (n = 162) completed a questionnaire about their home language use and beliefs about dual language development, and elementary-age children (N = 190)-Kindergarten (M age = 5.71, SD = .56), second grade (M age = 7.52, SD = .31), and fourth grade (M age = 9.35, SD = .45)-completed conceptually-scored vocabulary assessments. Principal component analyses revealed that Spanish-speaking parents' beliefs about dual language development are heterogeneous. Further, parents' beliefs can be characterized differently according to their children's English proficiency designations and grade levels. Structural equation modeling analyses revealed that the Bilingual Facility parental belief factor was associated with home language use practices, which in turn were associated with children's vocabulary. However, this association only applied to limited English proficient students and their parents. These results underscore the importance of attending to Spanish-speaking parents' beliefs, as they appear to relate to home language use practices and, importantly, they also relate to their children's vocabulary achievement.

Prefrontal White Matter Abnormalities Associated With Pain Catastrophizing in Patients With Complex Regional Pain Syndrome.

OBJECTIVE: To investigate altered prefrontal white matter integrity in complex regional pain syndrome (CRPS) and its relation with the degree of pain catastrophizing. DESIGN: Cross-sectional study. SETTING: University hospital. PARTICIPANTS: Twenty-one CRPS patients and 49 patients without CRPS (N=70). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The fractional anisotropy values within the prefrontal regions reflecting the structural integrity of white matter were measured in CRPS patients and patients without CRPS using diffusion tensor imaging. The degree of pain catastrophizing was also evaluated in CRPS patients. RESULTS: The structural integrity of the prefrontal white matter was lower in CRPS patients than in patients without CRPS (P=.03). In addition, lower structural integrity in the prefrontal cortex was correlated with a higher degree of pain catastrophizing among CRPS patients (r= -0.54, P=.01). CONCLUSIONS: Our findings suggest that pain catastrophizing, which is frequently reported in patients with CRPS, may be associated with the dysfunction of the prefrontal white matter.