Changes in Smoking Habits and Behaviors Following the Introduction and Spread of Heated Tobacco Products in Japan and Its Effect on FEV1 Decline: A Longitudinal Cohort Study

BackgroundHeated tobacco product (HTP) use in Japan has rapidly increased. Despite this rapid spread, little is known about the health effects of HTP use. We conducted a longitudinal cohort study to investigate the change in smoking habits following the spread of HTP use and its effect on forced expiratory volume in 1 second (FEV₁) decline.MethodsParticipants consisted of a resident population (n = 2,612; mean age, 67.7 years) with FEV₁ measurement in 2012–2014 and 2018–2019, and a worksite population (n = 722; mean age 49.3 years) without FEV₁ data. Participants were categorized as combustible cigarette-only smokers, HTP-only users, dual users, past smokers, and never smokers. The association between smoking group and the change in smoking consumption over a mean 5.6 years was examined. Differences in annual FEV₁ change between smoking groups were examined in the resident population.ResultsPrevalence of HTP-only and dual users in 2018–2019 was 0.8% and 0.6% in the resident population, and 5.0% and 1.9% in the worksite population, respectively. The overall number of tobacco products smoked/used increased in dual users compared to baseline, but not in others. Annual FEV₁ decline in dual users tended to be greater than that in cigarette-only smokers (16; 95% confidence interval, −34 to 2 mL/year after full adjustment). Participants switching to HTP-only use 1.7 years before had a similar FEV₁ decline as cigarette-only smokers.ConclusionsHTP use, including dual use, is prevalent even in a rural region of Japan. Dual users appear to smoke/use tobacco products more and have a greater FEV₁ decline. Tobacco policy should consider dual use as high-risk.Key words: heated tobacco products, electronic nicotine delivery devices, prevention, smoking caused disease     

Merits and Demerits of Operative Procedure to the Trachea in Patients with Differentiated Thyroid Cancer

Local radical thyroidectomy, including cervical lymph node dissection and combined circumferential resection of the trachea, has been performed over the past 20 years in 31 patients with differentiated cancer invading the trachea. The 5- and 10-year survival rates for these patients were 77.4% and 66.7%, respectively. In 19 of the 31 (61%) cases the recurrent nerve was resected because of direct cancer invasion. Bilateral recurrent nerve palsy occurred in 12 patients, 3 of whom were managed postoperatively using a T-shaped tube for preservation of the larynx. Hoarseness remained in 21 patients. In two patients with recurrent cancer invasion of the larynx, partial laryngectomy and hemilaryngectomy were performed, and reconstruction was done using ear cartilage without postoperative dyspnea or dysphagia. Parathyroid function is an important factor in regard to the quality of life of patients. In 22 patients at least one of the parathyroids was preserved. Postoperative calcium administration was necessary in 14 patients. Our long-term observations indicate that local radical thyroidectomy with combined resection of the trachea can serve as a useful treatment for advanced differentiated cancer invading the airway.     

Longitudinal evaluation of local muscle conditions in a rat model of gastrocnemius muscle injury using an in vivo imaging system

This study aimed to evaluate the time course of local changes during the acute phase of gastrocnemius muscle strain, in a rat model, using an in vivo imaging system. Thirty‐eight, 8‐week‐old Sprague‐Dawley male rats were used in our study. Experimental injury of the right gastrocnemius muscle was achieved using the drop‐mass method. After inducing muscle injury, a liposomally formulated indocyanine green derivative (LP‐iDOPE, 7 mg/kg) was injected intraperitoneally. We evaluated the muscle injuries using in vivo imaging, histological examinations, and enzyme‐linked immunosorbent assays. The fluorescence peaked approximately 18 h after the injury, and decreased thereafter. Histological examinations revealed that repair of the injured tissue occurred between 18 and 24 h after injury. Quantitative analyses for various cytokines demonstrated significant elevations of interleukin‐6 and tumor necrosis factor‐α at 3 and 18 h post‐injury, respectively. The time course of fluorescence intensity, measured using in vivo imaging, demonstrated that the changes in cytokine levels and histopathologic characteristics were consistent. Specifically, these changes reached peaked 18 h post‐injury, followed by trends toward recovery. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1034–1038, 2015.     

Multivessel coronary revascularization with bilateral internal thoracic artery grafts

Sixteen patients underwent coronary revascularization with bilateral internal thoracic artery (ITA) grafts between 1988 and 1989 at the Okayama University Hospital. A total 39 coronary grafts were performed, being an average of 2.4 grafts per patient. Each patient received bilateral ITA grafts, and in 5 patients an additional 7 grafts were constructed with 5 autologous veins and 2 gastroepiloic arteries. The right ITA was grafted as a free graft in 4 patients. The ITA graft patency rate was 96.8 per cent (31/32) at the time of hospital discharge. The postoperative morbidity included one reoperation for bleeding and one myocardial infarction. Coronary artery bypass grafting with bilateral ITA grafts can be safely performed and its application facilitates complete revascularization with arterial grafts.     

Effect of sound intensity on tonotopic fMRI maps in the unanesthetized monkey

The monkey's auditory cortex includes a core region on the supratemporal plane (STP) made up of the tonotopically organized areas A1, R, and RT, together with a surrounding belt and a lateral parabelt region. The functional studies that yielded the tonotopic maps and corroborated the anatomical division into core, belt, and parabelt typically used low-amplitude pure tones that were often restricted to threshold-level intensities. Here we used functional magnetic resonance imaging in awake rhesus monkeys to determine whether, and if so how, the tonotopic maps and the pattern of activation in core, belt, and parabelt are affected by systematic changes in sound intensity. Blood oxygenation level-dependent (BOLD) responses to groups of low- and high-frequency pure tones 3–4 octaves apart were measured at multiple sound intensity levels. The results revealed tonotopic maps in the auditory core that reversed at the putative areal boundaries between A1 and R and between R and RT. Although these reversals of the tonotopic representations were present at all intensity levels, the lateral spread of activation depended on sound amplitude, with increasing recruitment of the adjacent belt areas as the intensities increased. Tonotopic organization along the STP was also evident in frequency-specific deactivation (i.e. “negative BOLD”), an effect that was intensity-specific as well. Regions of positive and negative BOLD were spatially interleaved, possibly reflecting lateral inhibition of high-frequency areas during activation of adjacent low-frequency areas, and vice versa. These results, which demonstrate the strong influence of tonal amplitude on activation levels, identify sound intensity as an important adjunct parameter for mapping the functional architecture of auditory cortex.     

Enhanced Antitumor Efficacy of Vasculostatin (Vstat120) Expressing Oncolytic HSV-1

Oncolytic viral (OV) therapy is a promising therapeutic modality for brain tumors. Vasculostatin (Vstat120) is the cleaved and secreted extracellular fragment of brain-specific angiogenesis inhibitor 1 (BAI1), a brain-specific receptor. To date, the therapeutic efficacy of Vstat120 delivery into established tumors has not been investigated. Here we tested the therapeutic efficacy of combining Vstat120 gene delivery in conjunction with OV therapy. We constructed RAMBO (Rapid Antiangiogenesis Mediated By Oncolytic virus), which expresses Vstat120 under the control of the herpes simplex virus (HSV) IE4/5 promoter. Secreted Vstat120 was detected as soon as 4 hours postinfection in vitro and was retained for up to 13 days after OV therapy in subcutaneous tumors. RAMBO-produced Vstat120 efficiently inhibited endothelial cell migration and tube formation in vitro (P = 0.0005 and P = 0.0184, respectively) and inhibited angiogenesis (P = 0.007) in vivo. There was a significant suppression of intracranial and subcutaneous glioma growth in mice treated with RAMBO compared to the control virus, HSVQ (P = 0.0021 and P < 0.05, respectively). Statistically significant reduction in tumor vascular volume fraction (VVF) and microvessel density (MVD) was observed in tumors treated with RAMBO. This is the first study to report the antitumor effects of Vstat120 delivery into established tumors and supports the further development of RAMBO as a possible cancer therapy.     

Acoustic Impedance Analysis with High-Frequency Ultrasound for Identification of Fatty Acid Species in the Liver

Acoustic properties of free fatty acids present in the liver were studied as a possible basis for non-invasive ultrasonic diagnosis of non-alcoholic steatohepatitis. Acoustic impedance was measured for the following types of tissue samples: Four pathologic types of mouse liver, five kinds of FFAs in solvent and five kinds of FFAs in cultured Huh-7 cells. A transducer with an 80-MHz center frequency was incorporated into a scanning acoustic microscopy system. Acoustic impedance was calculated from the amplitude of the signal reflected from the specimen surface. The Kruskal–Wallis test revealed statistically significant differences (p < 0.01) in acoustic impedance not only among pathologic types, but also among the FFAs in solvent and in cultured Huh-7 cells. These results suggest that each of the FFAs, especially palmitate, oleate and palmitoleate acid, can be distinguished from each other, regardless of whether they were in solution or absorbed by cells.     

Promotion of IL-8 production in PMA-stimulated HL-60 cells by sesquiterpene quinones from a marine sponge, <Emphasis Type="Italic">Hippospongia</Emphasis> sp.

An extract of a marine sponge, Hippospongia sp., collected in Palau has inhibitory activity against colony formation by Chinese hamster V79 cells. Bioassay-guided isolation gave eleven sesquiterpene quinones. Compounds 1–8 inhibited colony formation by V79 cells with EC₅₀ values between 0.6 and 2.8 μmol L⁻¹. Their effects on the production of an inflammatory cytokine, IL-8, in tetradecanoyl phorbol acetate (PMA)-stimulated HL-60 cells were also investigated, because IL-8 production is sometimes correlated with inhibition of cell growth. Ilimaquinone (1) and its 5 epimer (2) had similar activity against V79 cells (EC₅₀ = 2.8 and 2.3 μmol L⁻¹, respectively) but did not modulate IL-8 production even at 10 μmol L⁻¹. Smenospongidine (3) and its 5 epimer (4), smenospongiarine (5) and its 5 epimer (6), and smenospongine (7) and its 5-epimer (8), at 10 μmol L⁻¹, promoted IL-8 production. Compounds 3, 5, and 7 had slightly stronger activity against V79 cells (EC₅₀ = 0.6, 1.7, and 0.8 μmol L⁻¹, respectively) than the corresponding 5 epimers 4, 6, and 8 (EC₅₀ = 0.8, 2.3, and 2.0 μmol L⁻¹, respectively). A similar structure–activity relationship was observed for promotion of IL-8 production. This is the first report of modulation of IL-8 production by these sesquiterpene quinones.     

Antioxidant effects of 1,5-anhydro-D-fructose, a new natural sugar, in vitro

The antioxidant effects of 1,5-anhydro-D-fructose (1,5-AF), a unique anhydrohexulose, were studied in 1,1-diphenyl-2-picrylhydrazyl (DPPH) solution, in human cells along with lipid peroxidation of low-density lipoprotein (LDL). We have confirmed that 1,5-AF scavenges DPPH radicals directly in solution and inhibits the formation of hydrogen peroxide and superoxide anion, typical reactive oxygen species (ROS), induced by phorbol myristate acetate (PMA) in a dose-dependent manner in THP-1 cells. We also observed the dose-dependent antioxidant effects of 1,5-AF on copper-mediated LDL oxidation. These findings suggest that 1,5-AF might play a role in reducing the risk of atherosclerosis and may help prevent coronary heart disease.